MXPA00010052A - The construction of copolymer libraries - Google Patents

Abstract

A multidimensional copolymer array of a plurality of copolymers, polymerized from at least two independently variable sets of monomers, is created. The homologous variations of the monomer series are selected to determine the effect of varying the structural features of the copolymer on at least one end-use property of the copolymer. Methods for determining the effects as a function of variation within the monomer series and identifying members having useful properties are also disclosed.

Description

BUILDING GENOTECTIONS OF COPOLI MEROS CROSS REFERENCE TO RELATED REQUEST The present invention claims the priority benefit of the E.U.A patent application. serial number 60/081, 502, the description of which is incorporated in the present invention for reference.

GOVERNMENT LICENSE RIGHTS • 10 The government of E.U.A. has a license with rights paid in this invention and the right in limited circumstances to require the owner of the patent to transfer to third parties on reasonable terms as required by the terms of the concession number GM-49849 granted by the National Institutes of Health.

• BACKGROUND OF THE INVENTION The present invention relates to the construction of banks of polymers based on the design principle of introducing systematic variations in the structure of a copolymer in at least two separate and independently variable domains within the structure of the copolymer. The methodology of the invention is broadly applicable to the development of copolymers in which complex requirements require careful optimization of the copolymer structure. This invention is also related to the preparation of tyrosine derivative monomers such as described in the patent E.U.A. No. 5,587,507 and to the preparation and use of polyarylates as described in the E.U.A. No. 5,216,115 and 5,317,077, which are incorporated in the present invention for reference. Combination methods that have led to dramatic changes in the manner in which vanguard compounds are identified for the discovery of new drugs are described by Lowe, JCS Reviews, 309-317 (1995). As is commonly practiced in the pharmaceutical industry, combination schemes are used to create a large number of structurally related compounds (usually within a single reaction vessel) followed by the identification of potential leading compounds in a selective bioassay. Such combination schemes are described by Mischer, ChemTracts-Org. Chem., 8 (1), 19-25 (1995). This method can not be easily applied to the design of engineering polymers or biomaterials. Starting with a monomer mixture and creating a large number of different polymers within the same reaction vessel could result in a polymer mixture that would be difficult to separate into individual compounds. Although in EP 789, 671 such methods are described as being useful for the design of polymers with catalytic activities, these methods are not useful for the design of polymers in which the individual properties of the material need to be optimized. The correlations between the structure and the properties of the • Polymers have been explored since the early 1930s when the macromolecular structure of polymers was first recognized. Sometimes, materials are studied in "sets" of materials not structurally related. For example, the study of tensile strength of glass, iron, paper, wood, and polyethylene can lead to the identification of a material with appropriate strength for any However, given the lack of any lack of any systematic variation in the structure between the test materials, it is generally impossible to draw some useful conclusions from one such study. Ertel et al., J .. Biomed. Mater. Res., 28, 919-930 (1994) illustrates a study design a little more sophisticated. A group of 4 polymers having identical skeletal structures but differing in the length of an alkyl ester pendant chain attached to the polymer backbone in each repeating unit was investigated. In this study, a relatively small number of polymers were compared and conclusions were drawn valid with respect to the effect of increasing the length of the hanging chain on the selected properties of the polymer such as the glass transition temperature, the chemical degradation rate, etc. It is estimated that hundreds of studies of this type have been reported in the literature. The main limitation of this study design is that only one structural variable can be explored. A more complex study design tries to correlate • the effect of two or more structural variables on a set of 5 properties of selected materials. For example, in the field of polyacrylic acid derivatives, a limited number of studies have attempted to correlate the effect of simultaneous variations within the chemical structure of the acrylate pendant chains. Although such studies are known in the literature, the general paradigm of synthesis of combination to the synthesis of combination of copolymers with defined systematic and structural characteristics. In terms of the requirements for a polymer bank design this method is unknown in the prior art. Menger et al., J. Orq. Chem., 60, 6666-6667 (1995), exposed a preformed polymer with pendant chains reactive to a reaction mixture containing a series of different reagents. As the random copying procedure was initiated, random sequences of hanging chains were attached to the skeleton of the pre-existing polymer. In essence, this is a method in which a non-traceable mixture of hanging chain sequences, all at the same time. The individual sequences could not be isolated and structurally defined materials were not obtained. In contrast, the entire mixture was tested for specific catalytic activity and it was impossible to detect which of the particular pendant chain sequences was responsible for any observed catalytic activity. Considering the cost and time required to identify • polymeric materials carefully designed and optimized as 5"specialty polymers" in many different industrial, medical and scientific applications, there is a great need to develop new paradigms and methods that can (1) increase the number of candidate polymers available for any specific application and (2) to systematize the study of correlations between polymer structure on the one hand and • 10 performance properties of the material on the other.

BRIEF DESCRIPTION OF THE INVENTION The present invention fulfills this need. An important aspect of this invention is that monomer systems are used in such a way that a large number of polymers can be synthesized in a parallel form so that each polymer contained within the resulting polymer bank is obtained in pure form on its own. reaction vessel. One of the important advantages of this method is that banks of 20 polymers are obtained that facilitate the establishment of simple and useful correlations between the systematic changes in the chemical composition of the polymers on the one hand and a wide range of physicomechanical and biological properties on the other hand. other.

The practical utility of this method depends on a chemical design that provides the formation of copolymers of type A-B, or A-B-C, etc. In the example of type A-B copolymers, two sets of reagents Am and Bn > the • Copolymerization in all possible combinations of all 5 monomers from set A with all monomers from set B will give a polymer bank with a total of A x B products. It has now been established that if monomers A and B possess the deliberate structural design characteristics, the resulting polymer bank will be provided with permutations that report these characteristics. # 10 The utility of this method in large arrays of polymers, in accelerated growth, with systematically variable properties can also be illustrated by the extension of this principle to polymers that are obtained from more than two monomeric species. For example, using a terpolymer design A-B-C, the copolymerization of an assembly of 10 A with 10 B and 10 C will give rise to 1000 different combinations. For reasons of clarity, the following discussion is strictly limited to • alternating copolymers of type A-B with the understanding that the principles discussed can easily be applied to alternating polymers obtained from more than two separate monomeric species. 20 Therefore, in accordance with the present invention, it is currently possible to copolymerize a set of monomers obtained from a structural template, with another set of monomers obtained from a different structural template, so that the copolymerization of all the elements of the first set with all the elements of the second set in a parallel preference synthesis will lead to a copolymer bank in which the individual elements of the copolymer bank exhibit unusually regular and systematic variations in the important end-use properties. Therefore, in accordance with one aspect of the present invention, there is provided a multidimensional copolymer array comprising a plurality of copolymers polymerized from at least two sets of independently variable monomers, in which the polymerization is characterized by: (a) the selection of a first series of monomers that vary in homologous form that have polymerizable non-variable functional groups; (b) the selection of at least one series of monomers varying in homologous manner having non-variable polymerizable functional groups and which are reactive with the polymerizable functional groups of the first series of monomers to form copolymers, and (c) reacting separately a plurality of monomers from the first series of monomers with a plurality of monomers from each of the additional monomer series to form the plurality of copolymers; wherein the homologous variations of the monomer series are selected to determine the effect of independently varying at least two different structural characteristics of the copolymer on at least one of the end-use properties of the copolymer.

The copolymers include both copolymers of the condensation type and copolymers prepared by polymerization with free radicals. The homologous variations within each series of • monomers are preferably selected to minimize any effect on the reaction capacity of the polymerizable functional groups of the monomers within each series. For the purposes of the present invention, the homologous series are defined not only as those which refer to the substituent groups in a series of monomers, but also to those which • 10 include variations within the structure of the monomer skeleton such as the introduction of unsaturations, the inclusion of additional methylene units, the replacement of a methylene carbon with a nitrogen or any appropriate atom, the replacement of a methylene unit with an atom of oxygen or sulfur, or any other appropriate atom, replacement of a methylene unit with another unit including, but not limited to, a keto unit, an amide unit, or an ester unit, and the like. For the purposes of the present invention, hydrogen is treated as an element of the series of homologous substituents. To obtain a polymer bank in which the properties As selected end-users change in a predictable and systematic manner, monomer assemblies A and B should be designed to provide complementary structural variations. Preferred end-use target properties for research include glass transition temperature, surface tension, and biological interaction with living cells. The exclusive utility of such polymer banks is twofold. The method as described in the present invention can be used to (1) increase the number of candidate polymers available to be evaluated with respect to any specific application and (2) systematize the study of correlations between the polymer structure, the properties of end use and performance. Therefore, in accordance with another aspect of the present invention, there is provided a method for determining the effect of independently varying at least two different structural characteristics of a copolymer on the end-use property of the copolymer, which method includes steps of: (a) measuring at least one end-use property of each of a plurality of copolymers prepared in accordance with the present invention; and (b) comparing the variations in each of the end-use properties measured for each of the copolymers as a function of the homologous variation within the series of monomers from which the copolymers were polymerized, to determine any relationship between homologous variations and variations in end-use property among the copolymers; whereby the specific elements of the plurality of copolymers having useful properties for specific end uses are identified.

Through the use of the methodology of the invention it was unexpectedly discovered that polyarylate copolymers, which are prepared by the condensation of a diphenolic compound obtained from tyrosine and a dicarboxylic acid, and having an ether linkage either in the backbone of the polymer or in the side chain of the polymer, are good substrates for cell growth despite being very hydrophobic. Therefore, in accordance with another aspect of the present invention, polyarylates having repeating units with the structure of formula I are provided: wherein R is selected from saturated and unsaturated, substituted and unsubstituted alkyl and alkylaryl groups containing up to 18 carbon atoms; Ri is selected from -CH = CH-, (-CH2-) a and -CHN (L1L2) - > in which "a" has a value from zero to eight, inclusive, and Li and L2 are independently selected from hydrogen and straight and branched alkyl and alkylaryl groups having up to 18 carbon atoms, with the proviso that Li and L2 are not both hydrogen; b independently has a value from zero to eight, inclusive; and R2 is selected from hydrogen and straight and branched alkyl and alkylaryl groups containing up to 18 carbon atoms; where one or more of R, and R2 and, when Ri is -CHNL. L2, Li and L2, contain at least one ether bond. The polyarylate copolymers of the present invention having side chains containing ether linkages are the condensation product of a dicarboxylic acid with a diphenol compound derived from tyrosine having at least one side chain containing at least one ether linkage. These diphenol compounds are novel and not evident in view of their unexpected ability to condense with a dicarboxylic acid to form a polyarylate copolymer which unexpectedly is a good substrate for cell growth and also very hydrophobic. Therefore, in accordance with another aspect of the present invention, a diphenol compound derived from tyrosine having the structure of formula II is provided: wherein Ri R2, and b are the same as described above with respect to formula I, with the proviso that R2, and / or, when R1 is -CHNL1L2, at least one of Li and L2, contains at least minus an ether link. A more complete appreciation of the invention and many other intended advantages obtained by reference to the following detailed description of the preferred embodiment and the claims in conjunction with the accompanying drawings, which describe the principles of the invention and the best modes, can easily be obtained. that are currently contemplated to make them.

BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 shows the correlation between the glass transition temperature of the polymer (Tg) and the chemical structure of the polymer backbone (y axis) and the hanging chain (x axis); Figure 2 shows the correlation between the air-water contact angle (a measure of the hydrophobic character of the surface and the chemical structure of the polymer backbone) (y-axis) and of the hanging chain (x-axis); Figure 3 shows the general structure of the polyarylates according to the present invention; Figures 4a and 4b show the first and second homologous series of monomers used in the method of the present invention to create the polyarylate copolymers of the present invention; Figure 5a shows the correlation of Tg and the number of carbon atoms incorporated in the modification points of the polymer skeleton and the pendant chain, expressed as the total index of flexibility (TFI); Figure 5b shows the correlation between the air-water contact angle and the number of carbon atoms incorporated in the modification points of the polymer backbone and the pendant chain; Figure 6a shows the correlation between Tg and the number of carbon atoms incorporated at the point of modification of the pendant polymer chain; Figure 6b shows the correlation between Tg and the number of carbon atoms incorporated at the point of modification of the polymer backbone; Figure 7a shows the correlation between fibroblast proliferation and hydrophobic surface character for poly (DT ester) glutarate and poly (DT ester) glycolates; and Figure 7b shows the correlation between fibroblast proliferation and hydrophobicity of the surface for poly (DT ester) suberates and poly (DT ester) dioxaoctanedioates.

DETAILED DESCRIPTION OF THE PREFERRED MODALITY The general concept of the present invention and its application to the development of biomaterials is illustrated in the present invention for polyarylate copolymers prepared by the condensation of a diacid with a diphenol in accordance with the method described by the patent E.U.A.

No. 5,216,115, cited above, in which the diphenol compounds are reacted with aliphatic or aromatic dicarboxylic acids in a carbodiimide-mediated direct polyesterification using 4- (dimethylamino) pyridinium p-toluenesulfonate (DPTS) as a catalyst. Nevertheless, one skilled in the art will understand how this concept can be extended to other polymerization reactions by condensation or by free radicals for other end uses, in addition to the preparation of the biomaterials. For example, in addition to a series of monomers in which polymerizable functional groups are hydroxyl groups and carboxylic acids, other series of monomers suitable for use with the present invention in condensation type polymerization reactions include monomers having polymerizable functional groups of the type amino, ester, anhydride and socianate. The polymerizable functional group can also be activated to react with the polymerizable functional groups of the other series of monomers. When the polymerizable functional group of the first series of monomers is a hydroxyl or amino group, the appropriate monomer series to be used as the additional monomer series include the monomer series in which the polymerizable functional group is a carboxylic acid, an isocyanate, an ester group or an anhydride group. For the condensation reactions, in which two additional series of monomers are used, the second additional series of monomers includes alkylene oxide monomers. Examples of suitable alkylene oxide monomers include ethylene oxide, propylene oxide, isopropylene oxide, butylene oxide, isobutylene oxide, and random block and block copolymer segments thereof. Condensation type polymerization reactions include both the ether and the suspension type processes. However, the present invention also includes copolymers prepared by free radical processes including ion polymerization processes. The synthesis reactions can be carried out in solution or in volume and with or without a catalyst. The reaction products can also be further modified by chemical reactions or crosslinking. Such synthesis characteristics are well known to those skilled in the art and do not require further explanation. A particularly preferred series of monomers to be used as the first series of monomers are the diphenolic monomers obtained from tyrosine of the E.U.A. Nos. 5,587,507 and 5,670,602, the descriptions of which are also incorporated in the present invention for reference. Preferred diphenolic monomers are desaminotirosyl-tyrosine esters which are known as DT esters. For the purposes of the present invention, the ethyl ester is known as DTE, the benzyl ester as DTBn, etc. Both patents describe methods by which these monomers can be prepared. As indicated above, the diphenolic monomers can be used in the synthesis of the polyarylates described by the patent E.U.A. No. 5,216,115. The general structure of the polyarylates is shown in Figure 3. These materials are strictly alternating type A-B copolymers consisting of a diacid component (the "A" monomers) and a diphenolic component (the "B" monomers). The diacids allow the variation in the polymeric skeleton while the diphenols contain a portion that is attached and with which a hanging chain is varied. Although diphenol is a dimer obtained from tyrosine, it functions as an individual monomer unit in the condensation reactions of the present invention, so that the condensation product of diphenol with diacid is considered as a strictly alternating polyarylate copolymer when it is not uses a third series of homologous monomers. Each set of monomers is obtained from an individual structural template that was varied in accordance with the schemes shown in Figure 4. Care should be taken to include only those compounds within the monomeric sets of diacids and diphenols having a capacity of almost identical reaction in their reactive groups. In this way, it is expected that all polymers within the copolymer bank, when prepared under identical reaction conditions, reach comparable molecular weights. Based on the above selection criteria, a total of 8 different aliphatic diacids and 14 different diphenols were identified to be included in the monomer assemblies.

A rack of small reaction vessels is then mounted inside a bath stirred with water so that each reaction vessel contains one of the 8 x 14 = 112 different combinations of • monomers. Although the addition of monomers and reagents was performed in a manual manner in these initial feasibility studies, the process of delivering the appropriate monomers and reagents into the reaction vessels could easily be automated. The molecular weights (MW) for the complete bank of 112 polyarylates ranged from 50,000 to 150,000 g / mol. The capabilities of • 10 polydispersion of the polymer ranged from 1.4 to 2.0. These values indicate that all the polymers contained within the bank had sufficiently high molecular weights and polydispersity capacity sufficiently similar to allow significant comparisons of their respective material properties. All polymers had the chemical structure expected, as confirmed by 1H-NMR spectroscopy. Then at least one of the properties of use is measured • end of each polymer and the variations in each end-use property measured as a function of the homologous variations within the monomer series are compared to determine any relationship or lack of same between the homologous variations and the monomer series and the variations measured in the end-use properties for the resulting polymers. The end-use properties can be measured simultaneously, in series or separately selected. Measurement techniques include ELISA, SAM, chromatographic methods, DSC, TGA, DMA and TMA. You can also use microscopic techniques, as well as processing methods such as extrusion, solvent casting, compression molding, molding • by injection and micro encapsulation. 5 The end-use properties that can be measured are typically physical properties such as mechanical properties, viscoelastic properties, morphological properties, electrical properties, optical properties (such as polarization capacity), permeability to solutes and gas, the thermal properties (including the • 10 glass transition temperature and degradation properties), surface tension properties and the like. Examples of morphological properties include the properties of crystalline liquid, the formation of separated microdomains in the phases, the short-range and long-range order of the polymer chains and the like. The examples of properties electric include, dipole properties, piezoelectric properties, dielectric properties and the like. Other end-use properties that can be measured include, but are not limited to, antibacterial activity, blood compatibility, tissue compatibility, drug release characteristics, biological interactions with living organisms, specifically the ability to support the binding and proliferation of cells required for the construction of supports for tissue design, hydrolytic degradation in vivo, protein adsorption characteristics and the like. Even other end-use properties that could be measured include, but are not limited to, processing capacity, radiation stability, sterilization ability, adhesive properties, hydrophobic characteristics (as • measured by the air-water contact angle and other techniques), stability to specific reaction conditions and the like. For the purposes of the present invention, the end-use properties are also defined to include the use of the method of the invention to identify monomers for condensation-type polymerization reactions that are sufficiently miscible so that the condensation-type reaction is • 10 present under polymerization processing interfaces or in suspension conditions. Other end-use properties refer to self-assembly, aggregation (formation of micelles) and the formation of ordered networks (gels) in aqueous and organic solutions. These properties are controlled by the hydrophilic-hydrophobic balance of the monomers used in the design of copolymer banks and are measured by rheological studies in solution, dynamic light scattering or by visualization of self-assembled aggregates using microscopic techniques such as atomic force microscopy. 20 Major mechanical end-use properties include tensile strength, Young's modulus and resistance to relaxation. An important thermal property is the glass transition temperature. Other important end-use properties are surface tension, air-water contact angle as a measure of the hydrophobic character, and biological interactions with living cells. Figure 1 shows the glass transition temperature (Tg) and Figure 2 shows the contact angle values for each of the 112 polymers. These histograms illustrate how the values for Tg and for the contact angle varied more and more over a wide range. The Tg values varied from 2-91 ° C and increased in ranges of about 1 ° C from polymer to polymer while the air-water contact angles varied from 64-101 ° C and increased in intervals of approximately 0.5 °. C from polymer to polymer. There are two useful ways to create more detailed correlations that include a larger number of polymers. First, it is possible to maintain the composition of the polymeric skeleton constant while at the same time varying the polymeric pendant chain of the diphenol repeating unit. For example, all polymers prepared from succinic acid but carrying different pendant chain alkyl esters could be one such subgroup. Second, it is possible to look at polymer subgroups where the pendant chain remains constant while the polymer backbone obtained from said repeating unit of diacid is varied. All polymers that carry a pendant chain of methyl ester but that contain different diacids could be one such subgroup. Using this method, more detailed correlations were developed that examine the selected subsets of polymers within the copolymer bank. Figures 5a and 5b show the structure-property correlations within a subset of 72 polymers whose variable regions ("Y" and "R" in Figure 4) were aliphatic, non-oxygenated portions. The index of total flexibility (TFI) was defined as the number of carbon atoms incorporated in the modification points in the skeleton and in the hanging chain. The exclusion of polymers containing oxygen atoms within their variable regions made it possible to isolate the effects related to the steric bulk of the pendant chain and the mobility / flexibility of the pendant chain. • 10 polymeric skeleton. The Tg graphs and the contact angle values against TFI for these polymers are shown in Figure 5a. These graphs indicate that as TFI increases, the Tg values decrease exponentially and that the Tg values were modeled by the equation of curve adjustment shown in figure 5a. The air-water contact angles were correlated with TFI in a linear fashion (Figure 5b). In general, the • variation in the number of methylene groups in either the pendant chain or the skeleton were effective means to change Tg and the contact angle over a wide range and in a predictable manner. 20 Figures 6A and 6B show more specific correlations of Tg and the dependence of the contact angle on the chemical structure of the skeleton and the hanging chain, which are two graphs that illustrate how Tg varies with increasing numbers of groups methylene in the pendant chain and in the skeleton respectively. Each point in these graphs represents a specific polymer (excluding polymers with branched variable regions), aromatic and oxygenated "R" and "Y"). The Tg values decreased exponentially as methylene groups were added to either the pendant chain or the skeleton. The exponential curves are not intercepted and are similar, indicating that alterations in either the hanging chain or the skeleton produced a similar change in Tg. It is also worth mentioning from this polyarylate bank that the selected polymers have glass transition temperatures close to or below body temperature. Therefore, devices made from these polymers can be designed to either remain in a vitreous state or take a rubbery state when implanted. Figures 7a and 7b show an analogous set of graphs with respect to changes in the contact angle. On the contrary, there is a linear increase in the air-water contact angle as the methylene groups are added either in the pendant chain or in the skeleton. In addition, unlike the Tg ratios, alterations in the hanging chain or the skeleton produce different changes in the contact angle. The steeper curve slopes observed in the graph of the contact angle against the hanging chain suggest that the hydrophobic character of the surface was influenced more efficiently by varying the number of methylene groups in the pendant chain. Slopes were also larger for modifications on lower methylene homologs compared to higher homologs. • Therefore, the addition of methylene groups to the pendant chain 5 has a greater relative effect in the succinate polymers than in the sebacate polymers. It should be mentioned that such detailed and predictive correlations between the polymer structure and the physical properties normally can not be obtained in the absence of the combination method described in the present invention. • 10 The branching of the skeleton was studied with the series 3-methyl adipate of polymers. Maintaining the constant diphenolic pendant chain and varying the diacid skeleton was found to moderately affect the Tg ranging from an increase of 2 ° C to a decrease of 5 ° C with a general average decrease of 1 ° C. The branch of the chain The pendant was studied with the isobutyl and secbutyl esters, while maintaining the constant diacid skeleton, which caused an average increase of 6 ° C (range 3-10 ° C) in Tg on the linear pendant chain polymers. The branching in either the hanging chain or the skeleton has a little discernible influence on the hydrophobic character of the surface as measured by the air-water contact angle. Figures 1 and 2 show that the substitution of oxygen atoms in place of methylene groups in the diphenolic pendant chain and in the diacid skeleton has a significant effect on the glass transition temperature. Oxygen replacement in the diacid skeleton increased Tg. When comparing the series of polymers of glutarate with the series of diglycolate polymers, the replacement of an individual methylene group in the diacid skeleton with an oxygen atom resulted in, on average, 5 an increase of 8 ° C (range 2- 13 ° C) in the respective values of Tg. On the other hand, the replacement with oxygen in the diphenolic pendant chain decreased to Tg in a comparison of the DTG polymer series to the comparable polymer series DTO. The DTG series substituted with oxygen had an average Tg that was 13 ° C lower (range 11-15 ° C) than • 10 the fully hydrocarbon-based series of comparable DTO polymers. The substitution with oxygen in any of the skeletons of the diacid or the pendant chain of diphenol decreased the hydrophobic character of the surface of the polymers compared to the corresponding polymers having only methylene groups in their regions variables. All polymers obtained from dioxaoctanedioic acid had, on average, an air-water contact angle of 5o lower • (ranges 0-10 °) than that of the corresponding polymers obtained from suberic acid. Similarly, all the polymers in the bank with the oxygen-containing DTG pendant chain had contact angles air-water that on average were 10 ° C lower (range 2-17 ° C) than the contact angles of the corresponding DTO polymers. However, some polymers such as poly (DTD diglycolate) (air-water contact angle = 97 °) had extremely hydrophobic surfaces despite the replacement of a methylene group with an oxygen atom in the polymer backbone. The polyarylate bank covers a wide range of mechanical properties. In qualitative terms, the stiffer polyarylates have similar mechanical properties to poly (D, L-lactic acid), while the more flexible polymers within the bank have mechanical properties that resemble those of soft polysiloxanes. The mechanical properties of a subset of eleven polymers chosen to represent a range of glass transition temperatures from 28 ° C to • 10 78 ° C in intervals of approximately 5o is listed in Table 1 in the order of decreasing Tg. In this subset of materials, the Young's modulus varied between 0.28-1.68 GPa and the resistance to relaxation varied between 5.8-44.8 MPa. There are no observable increasing correlations between the polymer structure and the rigidity or resistance to relaxation. However, those polymers whose glass transition temperature was below 35 ° C showed a dramatic drop in stiffness and tensile strength that was • related to its imminent transition from the vitreous state to the gummy state.

TABLE I Mechanical properties at room temperature (22 ° C) of selected polyarylates One of the important aspects of this polymer bank is that some material properties remain reasonably constant throughout the entire bank. For example, all 112 polymers had decomposition temperatures (measured by TGA open tray, nitrogen atmosphere) above 300 ° C, all polymers are amorphous and easily soluble the common organic solvents (methylene chloride, chloroform, tetrahydrofuran, dimethylformamide). Therefore, all polymers contained in the bank can be easily processed by solvent casting, compression molding and extrusion. An unexpectedly systematic correlation between the polymer structure and the cellular response is a unique aspect of the polyarylate bank and was observed in an in vitro study of the proliferation of fibroblasts on the growth surface prepared from a subgroup of 42 test polymers that have a straight chain diphenolic pendant chain (methyl, ethyl, butyl, hexyl, octyl and dodecyl) in combination with seven straight chain diacid skeleton configurations. Although the polymers are degradable under physiological conditions, the release of contaminants or degradation products that can be leached is not observed and there is no loss of mass over a period of several months. The proliferation of fibroblasts varies from approximately that typically observed in polystyrene tissue culture boxes (TSPS), (poly (DMT glutarate) and poly (DMT succinate)) to a complete absence of any proliferation (poly (DTD adipate) and ( poly (DTD succinate)) In general, the proliferation of fibroblasts on materials obtained from non-oxygenated diacids present a strong, linear correlation with the contact angle (figure 7a and 7b). the curves, cell proliferation decreases as the air-water contact angle increases from 65-100 ° C. This is in accordance with the general observation that the more hydrophobic polymeric surfaces are poorer cell growth substrates for fibroblasts The proliferation of fibroblasts is more sensitive to the chemical structure of the polymer than to the measurement of absolute contact angle. The series of polymers that have a methyl ester pendant chain (DTM) are all excellent substrates of equivalent growth (average 91% proliferation of TCPS; range 79-115%) even when the contact angles vary from 66 ° to 77 °. Similarly, within the bank there are several polymers that have comparable contact angles that support widely varying levels of cell proliferation. For example, (poly (DTB sebacate) and (poly (DTH adipate) have an air-water contact angle of 84 °, although cellular proliferation (relative to TCPS) IS 58% AND 16% respectively. within each subgroup of polymers F 10 coming from the same diacid but having different pendant chains, the cell proliferation decreases in a linear manner as the methylene groups segregate successively to the pendant chain. However, this decrease is not directly correlated with the absolute measurement of contact angle of the surface and the slopes of the curves of regression are differences for one of the polymer subgroups. That is, the chemical structure of the diacid in the skeleton of • polymer modulates the cellular response to the hanging chains. In those polymers in which oxygen is replaced in the skeletons (glycolate and dioxaoctanedioate series), the proliferation of fibroblasts were much less sensitive to the hanging chain length and the hydrophobic character of the surface. This correlation is illustrated in Figures 7a and 7b by the extremely less negative curve of the linear curve fitting. All polymers that have oxygenated diacids in their skeleton are unexpectedly and uniformly good substrates for fibroblast growth without taking into account the hydrophobic character of the surface. A particularly impressive example of the effect of oxygen substitution on the cellular response is the direct comparison of (poly (DTD glutarate) and (poly (DTD diglycolate)) (FIG.7a) These two polymers have identical structures, except that replaced a single methylene group in the skeleton of (poly (DTD glutarate) with an oxygen atom in the (poly (DTD diglycolate).) This small structural change has very little effect on the general polymeric properties and the two polymers have contact angles virtually identical air-water of 96 ° and 97 ° respectively, however fibroblasts do not proliferate on (poly (DTD glutarate) to any significant degree, while substantial cell proliferation is observed on identical surfaces prepared from (poly (DTD diglycolate) This is a valuable finding because they show that careful polymer design makes it possible to "decouple" the correlation between the Hydrophobic r of the surface and cell proliferation. Ertel et al., J Biomed. Mat. Res., 24, 1637-1659 (1990), and Steele et al., J. Biomater. Sci. Polvmer Edn., 6 (6), 511-532 (1994), have reported that the incorporation of oxygenated species on the surface by plasma bright discharge can improve cell growth. This method incorporates oxygenated species in a random mode and is associated with a corresponding reduction in the air-water contact angle. In the polyarylate bank of the invention, the selective replacement of a single methylene group by an individual oxygen atom occurs in a specific position in the polymeric backbone and has little effect on the air-water contact angle while at the same time significantly improves the characteristics of cell growth in substrate. This finding is unprecedented in the current literature. Therefore, the present invention includes polyarylate copolymers having the structure of formula I in which R, Ri and R2 and b are the same as described above with respect to formula I and at least one of R, Ri and R2 contain an ether linkage. Preferably Ri is -CH2-CH2- and b is preferably one. When R contains an ether linkage, R2 is preferably hydrogen or an ethyl, butyl, hexyl, octyl, or benzyl group. When R contains an ether linkage, ether is preferably -CH2-O-CH2- or -CH2-O-CH2-CH2-O-CH2-. When R-1 or R 2 contain an ether bond, R preferably, when it is aliphatic, contains from 4 to 12 carbon atoms. When aromatic, R preferably contains from 8 to 14 carbon atoms. More preferably R is also selected such that the dicarboxylic acids from which the polyarylates are polymerized are important metabolites present in the highly biocompatible nature or compound. Preferred aliphatic dicarboxylic acids therefore include the intermediate dicarboxylic acids of the cellular respiration path known as the Krebs cycle. These dicarboxylic acids include alpha-ketoglutaric acid, succinic acid, fumaric acid, maleic acid and oxalacetic acid. Other preferred biocompatible materials include sebacic acid, adipic acid, oxalic acid, malonic acid, glutaric acid, pimelic acid, suberic acid, and azelaic acid. Among the preferred aromatic dicarboxylic acids are terephthalic acid, isophthalic acid and bis (p-carboxyphenoxy) alkanes such as bis (p-carboxyphenoxy) propane. More preferably R is selected from -CH2-C (= O) -, -CH2-CH2-C (= O) -, -CH = CH- and (-CH2-) Zl in which z is a whole between two and eight, inclusive. Ri may contain an ether linkage when it is any of - CHNHLi or -CHNL? L2, in which at least one ether linkage is located in the alkyl group of Li or L. When either Ri or R2, with an ether bond, the preferred portion is -CH2-CH2-O-CH2-CH2-O-CH2-CH2-OH. The polyarylate copolymers according to the present invention have weight average molecular weights between about 20,000 and 400,000 daltons, and preferably about 100,000 daltons measured by GPC relative to the polystyrene standards without further correction. The diphenolic monomers obtained from tyrosine in which any of R-i or R2 contain at least one ether linkage are also included within the scope of the present invention. Such monomers have the structure of formula II, in which R1 or R2 and b are the same as described above with respect to formula II. R1 is preferably -CH2-CH2- in which case R2 will contain an ether bond, preferably the group -CH2-CH2-O-CH2-CH2-0-CH2-CH2-OH. If R-i is any of CHNHL, or -CHNL- | L2, in which, any of L1 or L2 contain at least one ether bond, then R2 is preferably hydrogen or an ethyl, butyl, hexyl, octyl or benzyl group. The preferred ether linkage portion for L1 or 5 L2 is also the aforementioned -CH2-CH2-O-CH2-CH2-O-CH2-CH2-OH. The two general characteristics of the above described polyarylate copolymer bank which dictate the choice of monomers were that the specific properties including Tg, contact angle, mechanical properties and cellular response should increasingly vary to F 10 across a broad range, and properties such as morphology, amorphous, hydrolytic susceptibility, processability and biocompatibility will remain broadly similar. The advantage of this juxtaposition of property variability is that structurally similar polymers can be used in applications that were related in some general forms, but triggered in others. There are significant economic incentives in this method to develop • polymers because once the material from a bank as such establishes itself through continuous rigorous successful evaluation (for example, FDA) for an application, other materials from the bank could then be more easily developed for other applications. The polyarylate copolymers described above were designed to be used in medical applications that require degradable materials. For example, a medical application may require a soft foldable material (low Tg) that is hydrophobic (low contact angle), while other applications may require a rigid material, relatively hard (higher Tg) in which it is hydrophilic, while both applications may require properties that are commonly shared among all bank materials such as processing capacity by molding, biocompatibility, degradability and amorphous morphology. For the polyarylate copolymers described above, the monomers were chosen to provide increasing differences in polymer free volume, mass, flexibility and hydrophobicity. The corresponding structural variations in the two sets of monomers did not affect the properties of the polymers in the same way. Therefore, the modifications to the monomer were complementary because the variation of the pendant chain does not have the same influence on the properties of the polymer as the modifications equal to the polymeric backbone. The three types of broad modifications on the pendant chain and skeletal structure were (1) simple homologous type variations to vary the number of methylene groups, (2) oxygen substitution by methylene groups, and (3) branching. The modifications of the pendant chain were all made with the diphenols obtained from tyrosine which were prepared by a common synthesis procedure while the modifications to the skeleton were achieved by the reasoned use of commercial diacids and hydroxyphenylalkyl acids. Similar modifications are expected to provide useful results with the poly (amide) esters of WO 98/36013, the disclosure of which is incorporated in the present invention for reference. Therefore, the present invention also includes poly (amide) esters having the structure: wherein R3 is selected from -CH = CH-, (-CH2-) a, and -CHN (L- | L2), in the • 10 which a has a value of zero to two, inclusive, and L? and L2 are independently selected from hydrogen and straight and branched alkyl and alkylaryl groups containing up to 18 carbon atoms, with the proviso that L-i and L2 are not both hydrogen. R5 and R & they are each independently selected from hydrogen and straight or branched alkyl groups having up to 18 carbon atoms and R4 is (-CH2-) b, in which b independently has a value between zero and eight, inclusive. R2 is selected from • straight and branched alkyl and alkylaryl groups containing up to 18 carbon atoms and R is selected from saturated and unsaturated, substituted and unsubstituted alkyl, aryl, and alkylaryl groups containing to 18 carbon atoms. At least one of R, R2, R5, Re and, when R3 is -CHNL? L2, L1 or L2, contain at least one ether linkage. R3 is preferably - (CH2-) a, with a being zero, and R5 and R6 are preferably independently selected from hydrogen and methyl. More preferably, at least one of R5 and Re is hydrogen, while the other, when it is not hydrogen, is methyl. The value for b is preferably one. Therefore, it is preferred that at least one of R and R2 • contain at least one ether link. The ether and non-ether type preferred species for R and R2 are the same as described above for the polyarylates of the present invention. Therefore the present invention also includes aliphatic-aromatic dihydroxy monomer compounds having the structure: in which R3 is -CH = CH-, (-CH2-) a and -CHN (L-? L2), in which a has a value of zero to two, inclusive, and L1 and L2 are independently selected from hydrogen and straight and branched alkyl and alkylaryl groups containing up to 18 carbon atoms, with the proviso that L1 and L2 are not both hydrogen, and R5 and R6 are each independently selected from hydrogen and of straight or branched alkyl groups having up to 18 carbon atoms. R4 is - (CH2-) b, in which b independently has a value between zero and eight, inclusive; and R2 is selected from straight and branched alkyl and alkylaryl groups containing up to 18 carbon atoms. At least one of R2, R5, Re and, when R3 is - CHNL? L2, L-i or L2, and, contain at least one ether linkage. The preferred species of R2, R3, R4, R5, e, a and are the same as described above with respect to the poly (amide) esters of the present invention. In the preferred dihydroxy monomer compounds, only R2 contains an ether linkage. A basic requirement is to prepare a sufficiently large quantity of each polymer with molecular weight high enough to establish the basic structure-property correlations. However, because a large number of polymers are F 10 required for this methodology, there are practical requirements to implement this methodology that the previous technique does not face. First, monomers that can be easily purified having comparable reaction capabilities in the polymerizable functional group are preferred so that the same polymerization conditions can be used to prepare the full bank. Secondly, in order to build polymer banks routinely, it is also of considerable importance F potential of automation of the complete procedure. Therefore, it is necessary to use mild reproducible polymerization conditions, which can be adapted to small scale reactions and of which the isolation and purification procedures are identical for each polymer. In order to reinforce the potential for automation, the isolation and purification procedures must be designed so that the individual polymers are never removed from the reaction vessel.

As indicated above, it is intended that the polyarylate copolymers be used in medical applications. A fundamental result of the methodology of the invention is that they are obtained • more significant biological correlations. In vitro correlations between the structure of the polymer and the proliferative response of rat lung fibroblasts were established. Although the cellular response selection studies of biomedical polymers have been conducted in the past, the lack of common structural characteristics among the test materials has prevented the identification of correlations between the F 10 chemical structure and cellular response. Because the polyarylate copolymers exhibited systematic variations in structure while sharing a range of common properties it was possible to correlate the biological response with definite changes in the chemical structure of the tested polymers. This is a method widely used in the industry Pharmaceutical for the development of small molecule drugs, although the prior art does not address this issue with respect to the development of # degradable polymeric biomaterials. Traditionally, the field of biomaterials has been based on the availability of convenience polymers instead of polymers specifically used for medical applications. This particular utility of the methodology of the invention is not associated in the prior art with the development of biomaterials. Although specific properties have been described that vary as a function of the structural modifications for the polyarylate copolymers, several properties remain essentially the same. In terms of processing capacity, all polymers were soluble in common organic solvents and could be coated by spin on glass. Various test polymers were made in solvent casting films, compression molded films and extruded bars and strips. All 112 polymers appeared as amorphous. The structural modifications that were imparted to the 112 polymers did not involve change in the hydrolytically labile portions. While the relative hydrolytic velocity of these portions could vary, the differences in velocity are not expected to be greater. Water absorption studies and preliminary degradation studies suggest that similar amounts of water are included in films made from various polymer banks with only small differences in the degradation speed. Finally, the studies also argued to a large extent that tyrosine-derived polyarylates are biocompatible.

• The methodology of the invention produced a bank that facilitates the selection of polymers for biomedical applications in ways that were not possible in the prior art. For example, polymers with an angle of air-water contact of approximately 70 ° often leads to optimal cell attachment and proliferation. From degradation of this polymer bank it is possible to choose polymers of similar structure having a contact angle of 70 ° which spans a large Tg space, including polymers that could be vitreous or gummy at body temperature. In other polymer subgroups, the glass transition can remain constant while the air-water contact angle can vary over a wide range. The following non-limiting examples set forth below illustrate certain aspects of the invention. All parts and percentages are given in mole percent unless otherwise indicated, and all temperatures are given in degrees Celsius. All solvents were HPLC grade. All other reagents were of analytical grade and used as received.

EXAMPLES EXAMPLE 1 Monomer synthesis Alkylstyrosine esters were coupled with 3- (4-hydroxyphenyl) -propionic acid (or in some cases, 4-hydroxyphenylacetic acid) using EDCI (1.0 eq.) And HOBt (0.1 eq) in a solution of N-methylpyrrolidinone-acetate. ethyl (1: 3; 1.5 M concentration in tyrosine ester) or acetonitrile (0.75 M concentration in tyrosine ester). After an aqueous treatment, the desaminotirosil-tyrosildiols 1 were obtained with purities of up to 99% (HPLC) and 98% (DSC). Most diacids 2 were commercially available with a purity of at least 99%. The diacids 2 with a lower purity were recrystallized.

EXAMPLE 2 Synthesis of polymer bank Small-scale polymerizations were carried out and worked completely in 20 ml glass flasks for chromatography with F 10 lids lined with PTFE. It was necessary to carefully weigh an equivalent of each diacid 2 and desaminotisolyl-tyrosyldiol 1 to ensure that the high molecular weight material was isolated. First the diacid in the container was weighed directly to minimize errors in mass transfer weight. Sufficient diacid 2 was used so that a The equivalent of desaminotyrosyl-tyrosyldiol 1 which typically weighs on a scale between 0.20 to 0.25 g could then be added to the container. Subsequently, dimethylaminopyridinium p-toluenesulfonate (0.06-0.08 g), methylene chloride (4 ml), and diisopropyl-carbodiimide (0.35 ml) were sequentially added to the vessel that was tightly capped and a piece of Parafilm® was placed.

The flasks were transferred to a Labline water bath stirrer (model 3540) and shaken at 250 rpm 30 ± 1 ° C for 36-48 hours. The treatment consisted in diluting each container reaction mixture in 16 ml of methanol, recapping the container and shaking vigorously to precipitate the polymer 3, then decanting the supernatant leaving the polymer in the container. The polymer was then dissolved in methylene chloride (1-2 ml) followed by the addition of methanol (18 ml) vigorous stirring to re-precipitate the • polymer and decant the supernatant. Methanol (5 ml) was added to the vessel and decanted as a final rinse. Polymer 3 was dried at room temperature under vacuum for 1 day, then under vacuum at 45 ° C for 1 day.

EXAMPLE 3 F 10 Synthesis of polymer at laboratory scale (5-50 g) An equimolar amount of desaminotyrosyl-tyrosyldiol 1 and diacid 2 were dissolved in methylene chloride at a concentration of 1.4 molar (in diol) in a 1 liter single-neck round bottom flask under a atmosphere of nitrogen. To this solution was added dimethyl aminopyridinium-p-toluenesulfonate (0.4 eq) followed by syringe addition of • diisopropyl carbodiimide (2.5 eq) after which the reaction in general became clear. After about 1 hour a precipitate became evident. The reaction was stirred for 24 to 36 hours and then transferred to a funnel The mixture was separated and slowly poured into a stirred solution (mechanical stirrer) of methanol (at least 10 volumes) to precipitate polymer 3. The supernatant was decanted and the polymer was transferred to a separatory funnel, dissolved in methylene (8-10% w / v), and precipitated in methanol or isopropanol (10 volumes). Again the supernatant was decanted and the polymer rinsed in methanol (or isopropanol). The polymer 3 was then dried under vacuum at room temperature for 2 to 3 • days, then vacuum at 45 ° C for 2 days.

Molecular weight determination The gel permeability chromatographic system consisted of either a Perkin Elmer model 250 pump or a Waters model pump 510, a Waters refractive index detector model 410, and either in two F 10 GPC PL-gel columns (pore size 105 and 103 Á) or two Waters columns Styragel 7.8x300 mm GPC (HR3 and HR4) operated in series at a flow rate of 1 ml / min in THF. The molecular weights were calculated in relation to the polystyrene standards without further correction using a program Waters Millenium Chromatography Manager on a personal computer Digital VenturisFP model 466. Filtered (PTFE, 0.45 ml syringe filter) . samples (5 mg / ml) before injection. The molecular weights and polydispersions for the polyarylate bank are shown in Table 2.

TABLE II Molecular weights (PMneso = 10 »3v) and polydispersions for the polyarylate bank Thermal Analysis / Differential Scanning Calorimetry (DSC): A thermal analyzer model DSC 910 (TA Instruments, Delaware) calibrated with indium was used to determine the glass transition temperature (Tg) of the polymer and the absolute purities of the monomer. For the measurement of Tg each specimen underwent two consecutive DSC scans with a heating rate of 10 ° C min "1. After the first run at 50 ° C on Tg, the specimen was extinguished with liquid nitrogen to at least 50 ° C below Tg and the second scan was obtained immediately, from which Tg was determined by the midpoint of the endothermic changes associated with the glass transition.The reproducibility of the Tg measurement was within 1 ° C for different specimens and batches of polymer The purity of the monomer was measured by heating a previously dried sample (50 ° C under vacuum) (2-3 mg) at a rate of 10 ° C min "1 until the temperature was approximately • 10 20 ° C below the melting point and then the heating rate was reduced to 1 ° C min "1 until the temperature reached about 10 ° C above the melting point. purity and depression were determined.The Tg values for the polyarylate bank are shown in the table 3.

• TABLE 3 Values Tq for the polyarylate bank • "10 fifteen Thermal analysis / thermocouraometric analysis (TGA): The decomposition temperature (Td) was determined by the thermogravimetric analysis in a TGA 951 (TA Instruments, Delaware) and was reported with a decrease of 10% in weight. The heating rate was 10 ° C min "1 and the average sample size was 30 mg.

Contact angle measurement The air-water contact angles were measured on a Rame-Hart model 100-00-115 goniometer using double distilled water as the probe. Water was coated onto coated glass coverslips by spinning with polyarylate in a low volume from above forming a sessile drop with a diameter of about 2.5 mm. The results were the average of at least 5 measurements (error + 1 ° C). The contact angle values for the polyarylate bank are shown in Table IV.

TABLE IV Values of contact angles for the polyarylate bank Table IV Continuation Preparation for the contact of the determination of the angle-glass covers coated by rotation Glass coverslips (18 mm diameter) were subjected to a sound treatment sequentially twice in solutions of 25% NaOH (10 minutes), HCl to 25% (10 minutes), and Micro detergent at 2% (30 minutes). The coverslips were rinsed abundantly after each sound treatment with distilled deionized water and after the final rinse they were subjected to sound treatment sequentially two times each in absolute ethanol (5 minutes) and then methylene chloride (5 minutes). The coverslips were then stored in a methylene chloride solution until they were needed to be coated by twist and handled carefully with tweezers or by the edge with the hand using disposable latex gloves. Each polyarylate solution was prepared by first adding about 20 to 30 mg of polymer to a bottle of - tared glass and adding enough methylene chloride to give a 2.5% (w / v) solution, which was then filtered (PTF syringe filter, 0.45 mm). The coverslips were removed from the methylene chloride solution and dried by rotation. The polymer solution was added to provide complete coverage of the glass surface which was then rotated for 20 seconds at 2000 rpm. The procedure was repeated two more times to ensure a uniform surface and then the coverslips were placed in individual disposable Petri dishes and dried at room temperature under vacuum before contacting the angle measurement.

Preparation of spin-coated glass coverslips for cell proliferation tests Glass coverslips (diameter 15 mm) were cleaned in the same manner as the coverslips used for contact angle measurement. After the final sound treatment in methylene chloride, the coverslips were rinsed twice in ethyl acetate and then subjected to a sound treatment twice (5 minutes) in a solution of poly (styrene-silane) -acetate copolymer. 2.5% ethyl (w / v). The coverslips were immersed in this solution for a further 10 minutes, then a coverslip was placed flat on top of Petri dishes and stored in a 60 ° C oven under vacuum for two days. After cooling to room temperature, the coverslips were removed from the oven in vacuo and rinsed in ethyl acetate (2x) and methanol (2x), and then ethyl acetate once again before drying on a thin sheet of shredded aluminum at room temperature. air for 30 minutes. The coverslips then • They were stored in a glass container until they were needed for the coating by turning. 2.5% (w / v) filtered methylene chloride (PTFE 0.45 mm syringe filter) solutions were used to spin-coat each glass coverslip twice to ensure a uniform surface. The polymer solution was added to promote complete coverage of the glass surface which was then spun F 10 for twenty seconds at 2000 rpm. The cover caps were handled with tweezers or by the edge with the hand using disposable latex gloves and carefully placed in individual cavities in 24 cavity cell culture plates with non-tissue culture treatment, which were subsequently stored at room temperature under vacuum until that were needed for its use.

• Cell proliferation test Coverslips of glass coated by spinning previously with each of the polymers, were placed on polystyrene plates with culture treatment that is not tissue. Four glass coverslips for each polymer (n = 4) were used in each test and the tissue culture polystyrene functioned as the control material. Using a culture technique for? 9 drip, 1x10 cells / cm in DMEM supplemented with inactive fetal bovine serum by 10% heat were seeded on each surface and incubated for one hour. After one hour as the fixation period, the cavities in each plate were washed with PBS to remove non-adherent cells, re-filled with the medium, and returned to the incubator. The number of fibroblasts present on each of the surfaces was taken after seven days with the commercially available MTS colorimetric test (Promega, Madison, Wl). The examples illustrate how the present invention can be used to establish a correlation between chemical structure and Tg, proliferation of fibroblasts and air-water contact angles. The characterization data of desaminotirosil-tyrosinadiols not previously reported in the literature are set forth below. All diols are variations of the general structure of Figure 3.

Ester L-tyrosin-N- (3- (4-hydroxyphenyl) -1-oxopropyD-methyl, DTM n = 2, R2 = CH3- (C19H2? NO5) Molecular weight, 343.39 Melting point (° C) 123-124 1 H-NMR (200 MHz, DMSO) d 9.25 (s, 1 H, phenol), 9.16 (s, 1 H, phenol), 8.27 (d, 1 H, amide), 6.96 (m, 4 H, aryl), 6.67 ( d, 4H, aryl), 4.40 (q, 1 H, α-proton), 3.59 (s, 3 H, -0-CH 3), 2.60-2.92 (m, 4 H, -CH 2 -), 2.33 (t, 2 H, -CH2-) .13H-NMR (50 MHz, DMSO) d 172.5, 171.9, 156.2, 155.6, 131.5, 130.2, 129.2, 127.5, 115.2, 54.1, 51.9, 37.3, 36.3, 30.4 Analysis calculated for: C, 66.46; H, 6.17; N, 4.08, Found: C, 66.39; H, 6.26; N, 3.97.

Ester L-Trosine-N-f3- (4-hydroxyphenyl) -1-oxopropyl-dodecyl. DTD n = 2, R2 = CH3 (CH2) n 'C3oH43N? 5 Molecular weight, 497.68 F 10 Melting point (° C) 93-94 1 H-NMR (200 MHz, DMSO) d 9.23 (s, 1 H, phenol ), 9.14 (s, 1 H, phenol), 8.25 (d, 1 H, amide), 6.96 (m, 4H, aryl), 6.65 (d, 4H, aryl), 4.38 (q, 1 H, α-proton) ), 3.59 (t, 2H, -O-CH2), 2.60-2.86 (m, 4H, -CH2-), 2.32 (t, 2H, -CH2-), 1.49 (bs, 2H, [O-CH2-] CH2-), 1.24 (s, 18H, -CH2-), 0.86 (bs, 3H, -CH3). 15 13C-NMR (50 MHz, DMSO) d 172.0, 171.8, 156.3, 155.7, 131.4, 130.2, 129.2, 127.4, 115.2, 64.2, 54.2, 37.3, 36.4, 31.6, 30.5, 29.3, 29.0, 28.9, # 28.3, 25.5, 22.4, 14.2. Analysis calculated for: C, 72.40; H, 8.71; N, 2.82. Found: C, 71.88, H, 8.58; N, 2.71 20 Ester L-Tyrosine-N- (3- (4-hydroxy-phenyl) -1-oxopropyl-isopropyl) DTiP n = 2, R2 = (CH3) 2CH- C21H25NO5 Molecular weight, 371.44 Melting point (° C) 79 (DSC) • 1 H-NMR (200 MHz, DMSO) d 9.24 (s, 1 H, phenol), 9.15 (s, 1 H, phenol), 8.22 (d, 1 H, amide), 6.96 (m, 4H, aryl), 6.67 (d, 4H, aryl), 4.84 (quint., 1 H, [0-CH3) 2j-H), 4.33 (q, 1 H, a-proton), 2.82 (t, 2H, -CH2-), 2.65 (t, 2H, -CH2-), 2.33 (t, 2H, -CH2-), 1.16 (d, 3H, -CH3), 1.06 (d, 3H, -CH3). 13 H-NMR (50 MHz, DMSO) d 171.8, 171.5, 156.2, 155.7, 131.5, F 130.3, 129.2, 127.4, 115.2, 68.0, 64.3, 37.3, 36.4, 30.4, 21.8, 21.6. 10 Analysis calculated for: C, 67.91; H, 6.78; N, 3.77. Found: C, 67.61, H, 7.19; N, 3.54.

Ester L-Tyrosine-N-. { 3- (4-hydroxyphenyl) -1-oxopropyl) -sobutyl, DTiB 15 n = 2, Rt CHskCH-CHa- C22H25N05 • Molecular weight, 385.46 Melting point (° C) 104.6 (DSC) 1 H NMR (200 MHz, DMSO) d 9.23 (s, 1 H, phenol), 9.15 (s, 1 H, phenol), 8.26 (d, 1 H, amide), 6.98 (m, 4H, aryl), 6.65 (d, 4H, aryl), 4.38 (q, 1 H, a-proton), 3.78 (d, 2H, -0-CH2-), 2.60-2.87 (m, 4H, -CH2-), 2.32 (t, 2H, -CH2-), 1.81 (m, 1H, [(-0-CH2) C (CH3) 2- ] H), 1.76 (d, 6H, -CH3). 13 H-NMR (50 MHz, DMSO) d 172.1, 171.8, 156.2, 155.6, 131.5, 130.2, 129.2, 127.5, 115.3, 70.3, 54.3, 37.3, 36.4, 30.4, 27.5, 19.0. Analysis calculated for: C, 68.55; H, 7.06; N, 3.63. Found: C, 68.60; H, 7.21; N, 3.55.

Ester L-Tyrosine-N- (3- (4-hydroxyphenyl) -1-oxopropyl-sec-butyl ester, DTsB n = 2, R2 = CH3CH2 CH (CH3) - Molecular weight, 385.46 Melting point (° C) 121 (DSC) 1 H-NMR (200 MHz, DMSO) d 9.24 (s, 1 H, phenol), 9.15 ( s, 1 H, phenol), 8.24 (d, 1 H, amide), 6.98 (m, 4H, aryl), 6.67 (d, 4H, aryl), 6.67 (d, 4H, aryl), 4.70 (m, 1 H, -O [(- CH2) C (CH3-] H), 4.35 (q, 1 H, α-proton), 2.60-2.90 (m, 4H, -CH2-), 2.32 (t, 2H, -CH2-), 1.45 (m, 2H, -CH2-), 1.08 (d, 3H, -CH3), 0.80 (dt, 3H, -CH3). 13 H-NMR (50 MHz, DMSO) d 171.9, 171.8, 156.2, 155.7, 131.5, 130.3, 129.3, 127.4, 115.2, 72.5, 72.3, 54.4, 54.3, 37.3, 36.4, 30.4, 28.4, 28.3, 19.4, 19.3, 9.6. Analysis calculated for: C, 68.55; H, 7.06; N, 3.63. Found: C, 68.35; H, 7.18; N, 3.59.

Ester L-Tyrosine-N- (3- (4-hydroxyphenyl) -1-oxopropyl.} - benzyl, DTBn n = 2, R2 ::: CH2C6 H5 C25H25N? 5 Molecular weight, 419.49 Melting point (° C) 113-115 .1H-NMR (200 MHz, DMSO) d 9.25 (s, 1H, phenol), 9.16 (s, 1H, phenol), 8.31 (d, 1H, amide), 7.30 (m, 5H, aryl), 6.97 (m, 4H, aryl), 6.65 (d, 4H, aryl), 5.07 (s, 2H, Ph-CH2-), 4.44 (q, 1 H, α-proton), 2.59-2.89 (m, 4H, -CH2-), 2.32 (t, 2H, -CH2-). 13 H-NMR (50 MHz, DMSO) d 171.9, 156.3, 155.7, 136.1, 131.5, F 130.3, 129.2, 128.6, 128.3, 128.1, 127.3, 115.3, 66.1, 54.3, 37.3, 36.3, 30.4 10 Analysis calculated for: C, 71.58; H, 6.01; N, 3.34. Found: C, 71.14; H, 6.31; N, 3.16.

Ester L-Tyrosine-N-f2- (4-hydroxyphenyl) -1 -oxoetiD-ethyl, THE C? 9H21N05 Molecular Weight, 343.39 • Melting Point (° C) 124-125. 1 H-NMR (200 MHz, DMSO) d 9.25 (s, 2H, phenol), 8.37 (d, 1 H, amide), 6.97 (t, 4H, aryl), 6.67 (d, 4H, aryl), 4.35 (q , 1H, α-proton), 4.05 (q, 20 2H, -0-CH2-), 3.31 (s, 2H, Ph-CH2-), 2.86 (m, 2H, -CH2-), 1.12 (t, 3H , -CH3), 13 C-NMR (50 MHz, DMSO) d 171.9, 170.9, 156.3, 156.0, 130.0, 130.1, 127.4, 126.4, 115.2, 115.1, 60.7, 54.2, 41.3, 36.3, 14.2. Analysis calculated for: C, 66.46; H, 6.17; N, 4.08. Found: C, 66.41; H, 6.31; N, 4.03. Ester L-tyrosine-N-f2- (4-hydroxyphenyl) -1-oxoetyl) -hexyl, HTH n = 1, R2 = CH3 (CH2) 5- C23H29NO5 Molecular weight, 399.50. Melting point (° C) 106-108. 1 H-NMR (200 MHz, CDCl 3) d 7.73 (bs, 1 H, phenol), 7.59 (bs, 1 H, phenol), 6.91 (d, 2 H, aryl), 6.64 (d, 6 H, aryl), 6.07 (d, 1 H, amide), 4.78 (q, 1 H, a-proton), 4.12 (t, 2 H, -0-CH2-), 3.46 (s, 2 H, Ph-CH2-), 2.93 ( m, 2 H, -CH 2 -), 1.62 (m, 2 H, -CH 2 -), 1.28 (bs, 6 H, -CH 2 -), 0.87 (bs, 3 H, CH 3). 13 C-NMR (50 MHz, CDCl 3) d 173.2, 172.6, 156.1, 155.8, 131.2, 130.6, 126.8, 125.6, 116.6, 116.2, 66.7, 53.6, 43.0, 37.1, 31.8, 28.9, 25.9, 22.9, 14.5. Analysis calculated for: C, 69.15; H, 7.32; N, 3.51. Found: _ C, 69.13; H, 7.33; N, 3.44.

Ester L-tyrosine-N-. { 2- (4-hydroxyphenyl) -1-oxoethyl) -octyl, HTO n = 1, R2 = CH3 (CH2) 7- C25H33N05 Molecular weight, 427.55 Melting point (° C) 59-61. 1 H NMR (200 MHz, CDCl 3) d 7.60 (bs, 2 H, phenol), 6.90 (d, 2 H, aryl), 6.67 (d, 6 H, aryl), 6.07 (d, 1 H, amide), 4.79 (q, 1 H, a-proton), 4.14 (t, 2 H, -O-CH2-), 3.46 (s, 2 H, Ph-CH2-), 2.93 (m, 2 H, -CH2-), 1.63 (bs, 2 H, -CH2-), 1.26 (s, 10 H, -CH2-), 0.86 (bs, 3 H, -CH3). 13 C-NMR (50 MHz, CDCl 3) d 173.2, 172.6, 156.1, 155.8, 131.2, 130.6, 126.8, 125.7, 116.6, 116.3, 66.7, 53.6, 43.0, 37.1, 32.2, 29.6, 28.9, 26.3, 23.1, 14.6. Analysis calculated for: C, 70.23; H, 7.78; N, 3.28. Found: C, 69.94; H, 7.46; N, 3.16.

Ester L-trosrosine-N-. { 3- (4-hydroxyphenyl) -1-oxopropyl > - (2- (2- F 10 ethoxyethoxyethyl, DTG n = 2, R2 = CH3CH20-CH2CH20-CH2CH2- C24H3? N07 Molecular weight, 445.53 Melting point (° C), oil at room temperature 15 1 H-NMR (200 MHz , CDCI3) d 7.62-7.50 (bs, 2 H, phenol), 6.88 (d, 2H, aryl), 6.70 (q, 6 H, aryl), 6.34 (d, 1 H, amide), 4.78 (q, 1 H, α-proton), 4.17 • (bs 2 H, -O-CH2-), 3.60 (bs, 6 H, -CH2-O-CH2-O-), 3.51 (q, 2 H, -0-CH2-methyl), 2.90 (m , 2 H, -CH2-), 2.76 (m, 2 H, -CH2-), 2.37 (m, 2 H, -CH2-), 1.16 (t, 3 H, -CH3) 20 13C-NMR (50 Mhz CDCI3) d 173.5, 172.2, 155.8, 155.1, 132.1, 130.8, 129.8, 127.3, 116.0, 70.9, 70.1, 69.2, 67.3, 53.9, 38.7, 37.3, 31.1, 15.5. Analysis calculated for: C, 64.70; H, 7.01; N, 3.14. Found: C, 64.88; H, 6.79; N, 3.03.

Ester L-tyrosine-n-r3- (4-hydroxyphenyl) -1-oxopropyl-1-y2- (2-ethoxyethoxyCetyl) DTG C24H31N07 • Molecular weight, 445.53 5 Melting point (° C) Boils at room temperature 1H-NMR (200 MHz, CDCl 3) d 7.62-7.50 (bs, 2 H, phenol), 6.88 (d, 2 H, aryl, 6.70 (q, 6 H, aryl), 6.34 (d, 1 H, amide), 4.78 (q, 1 H, α-proton), 4.17 (bs, 2 H, -O-CH2-), 3.60 (bs, 6 H, -CH2-0-CH2-CH2-0-), 3.51 (q, 2 H, -0-CH2-CH3), 2.90 ( m, 2 H, -CH 2 -), 2.76 (m, 2 H, -CH 2 -), 2.37 (m, 2 H, -CH 2 -), 1.16 (t, 3 H, -CH 3). 13 C-NMR (50 MHz, CDCl 3) d 173.5, 172.2, 155.8, 155.1, 132.1, 130.8, 129.8, 127.3, 116.0, 70.9, 70.1, 69.2, 67.3, 64.9, 53.9, 38.7, 37.3, 31.1, 15.5. 13 C-NMR (50 MHz, DMSO) d 171.9, 156.2, 155.7, 131.5, 130.3, 15 129.2, 127.4, 115.2, 70.1, 69.4, 68.4, 65.8, 64.0, 54.2, 37.3, 36.3, 30.4, 15.3. Analysis calculated for: C, 64,707; H 7.01; N, 3.28. Found: C, 64.88; H, 6.79; N, 3.03. The examples and description of the preferred embodiment should be taken as illustrative, not limiting, the present invention is defined by the claims. As will be readily apparent, various variations and combinations of features set forth in the description may be used without departing from the present invention as set forth in the claims below. Said variations should not be taken as a separation of the spirit and scope of the invention, and all such variations are intended to be included within the scope of the following claims. • • •

Claims (1)

1. NOVELTY OF THE INVENTION CLAIMS 1- A multidimensional copolymer array comprising a plurality of polymerized copolymers from at least two independently variable sets of monomers, wherein said polymerization is characterized by: (a) the selection of a first series that varies in a homologous manner from monomers with non-variable polymerizable functional groups; (B) the selection of at least one additional series that varies homologously from different monomers having non-variable polymerizable functional groups that react with the polymerizable functional groups of said first series of monomers to form copolymers; and (c) reacting separately a plurality of monomers from said first series of monomers with a plurality of monomers from each of said series of additional monomers to form said plurality of copolymers; wherein said homologous variations of said series of monomers are selected to determine the effect of independent variation of at least two different structural characteristics of said copolymer on at least one end-use property of said copolymer. 2. - The arrangement of copolymers according to claim 1, further characterized in that said polymerization reaction is a free radical process. 3. The arrangement of copolymers according to claim 2, further characterized in that said free radical process is an ionic polymerization. 4. The arrangement of copolymers according to claim 1, further characterized in that said separate reactions are carried out in parallel. 5. The arrangement of copolymers according to claim 1, further characterized in that said separate reactions are carried out in solution. 6. The arrangement of copolymers according to claim 1, further characterized in that said separate reactions are carried out in volume. 7. The arrangement of copoiomers according to claim 1, further characterized in that said separate reactions are carried out in the presence of a catalyst. 8. The arrangement of copolymers according to claim 1, further characterized in that said separate reactions are carried out in the absence of a catalyst. 9. The arrangement of copolymers according to claim 1, further characterized in that said copolymers are further modified by chemical reactions or between crossings. 10. An arrangement of multidimensional condensation type copolymers, comprising a plurality of polymerized copolymers • of at least two variable groups independently of monomers, wherein said polymerization is characterized by: (a) the selection of a first series that varies homologously from monomers with polymerizable non-variable functional groups; (b) the selection of at least one additional series that varies homologously from different monomers having functional groups • 10 non-variably polymerizable reactants with the polymerizable functional groups of said first series of monomers to form copolymers; and (c) reacting separately a plurality of monomers from said first series of monomers with a plurality of monomers from Each of said series of additional monomers to form said plurality of condensation type copolymers; wherein said homologous variations of said series of monomers are selected to determine the effect of the independent variation of at least two different structural characteristics of said copolymer on at least one property 20 of end use of said copolymer. 11. The arrangement of copolymers according to claim 10, further characterized in that said condensation type reaction is an interface procedure. 12. - The arrangement of copolymers according to claim 10, further characterized in that said condensation type reaction is a suspension process. 13. The arrangement of copolymers according to claim 10, wherein said separate reactions are performed in parallel. 14. The arrangement of copolymers according to claim 10, wherein said separate reactions are carried out in solution. • The arrangement of copolymers according to claim 10, wherein said separate reactions are carried out in volume. 16. The arrangement of copolymers according to claim 10, wherein said separate reactions are carried out in the presence of a catalyst. 17.- The arrangement of copolymers in accordance with the • claim 10, wherein said separate reactions are performed in the absence of a catalyst. 18.- The arrangement of copolymers in accordance with the Claim 10, wherein said polymerizable functional groups of said first series of monomers are amine or hydroxyl groups and said polymerizable functional groups of said additional series of monomers is selected from the group consisting of carboxylic acids, esters, anhydrides and isocyanates. 19. The arrangement of copolymers according to claim 18, wherein said additional series of monomers comprises • a second and third series of monomers, said second series of monomers is selected from the group consisting of carboxylic acids, esters, anhydrides and isocyanates, and said third series of monomers comprises a plurality of alkylene oxides selected from the group consisting of of ethylene, propylene oxide, isopropylene oxide, butylene oxide, isobutylene oxide and random polymers and copolymers and in • 10 block of them. 20. The arrangement of copolymers according to claim 18, wherein said polymerizable functional groups of said first series of monomers are hydroxyl groups and said additional series of monomers comprise a series of monomers with acidic groups 15 polymerizable carboxylic acids. 21.- The arrangement of copolymers according to the • claim 20, wherein said first series of monomers comprises a plurality of different diphenolic compounds, each having the general structure: HO- -R, - C-NH-CH-fCH9V- -OH OR2 where Ri is selected from the group consisting of -CH = CH-, (-CH2-) a, and -CHN (L? L2), where a has a value from zero to eight inclusive, and Li and L are independently selected from the group consisting of hydrogen and straight and branched alkyl and alkyl groups containing up to 18 carbon atoms, as long as Li and L2 are not both hydrogen; b independently has a value between zero and eight, inclusive; and R2 is selected from the group consisting of straight and branched alkyl and alkyl groups containing up to 18 carbon atoms. 22. The arrangement of copolymers according to claim 20, wherein said first series of monomers comprises a plurality of different aromatic-aliphatic dihydroxyl compounds, wherein each has the general structure: where R13 selects from the group consisting of -CH = CH-, (-CH2-) a, and -CHN (L? L2), where a has a value from zero to eight inclusive, and L1 and L2 is selected from independently of the group consisting of hydrogen and straight and branched alkyl and alkyl groups containing up to 18 carbon atoms, as long as L1 and L2 are not both hydrogen; R5 and Re each is independently selected from the group consisting of hydrogen and straight or branched alkyl groups having up to 18 carbon atoms, * is (-CH2-) b, wherein b has a value independently between zero and eight, inclusive; and R2 is selected from the group consisting of straight and branched alkyl and alkylaryl groups containing up to 18 carbon atoms. 23. The arrangement of copolymers according to claim 20, wherein said series of monomers with polymerizable carboxylic acid groups comprises a plurality of different dicarboxylic acid compounds, each having the general structure: O O II HO- C- R- C-OH wherein R is selected from the group consisting of saturated and unsaturated, substituted and unsubstituted aryl and alkylaryl alkyl groups containing up to 18 carbon atoms. The arrangement of copolymers according to claim 21, wherein for one or more of said monomers of said first series of monomers, at least one of R2, L1 or L2 contains at least one ether linkage. The arrangement of copolymers according to claim 22, wherein for one or more of said monomers of said first series of monomers, at least one of R2, Rs, Re U or L2 contains at least one ether linkage . 26. The arrangement of copolymers according to claim 23, wherein for one or more of said monomers of said series of dicarboxylic acid monomers, R contains at least one ether linkage. 27.- The arrangement of copolymers in accordance with the • claim 10, further characterized in that said copolymers are further modified by chemical reactions or cross-linking. 28. - A method for determining the effect of independent variation of at least two different structural characteristics of a copolymer in at least one end-use property of said copolymer, comprising: a) measuring at least one property of end use of each copolymer of said copolymer array according to claim 1; and b) comparing the variations in each end-use property measured for each of said copolymers as a function of the homologous variation within said series of monomers from which said copolymers were polymerized to determine any relationship between said homologous variations and said variations. of end-use property between said copolymers; in this way identify specific elements of said plurality of copolymers having useful properties for specific end uses. 29. The method according to claim 28, wherein said polymerization reaction is a free radical process. 30. The method according to claim 29, further characterized in that said free radical process is an ionic polymerization. 31. The method according to claim 28, wherein said separate reactions are performed in parallel. 32. The method according to claim 28, wherein said separate reactions are carried out in solution. 33. The method according to claim 28, wherein said separate reactions are carried out in volume. 34. The method according to claim 28, wherein said separate reactions are carried out in the presence of a catalyst. 35. The method according to claim 28, wherein said separate reactions are carried out in the absence of a catalyst. 36. The method according to claim 28, wherein said copolymers are further modified by chemical reactions or crosslinking. 37. The method according to claim 28, wherein said end-use properties are measured by ELISA, SAM, chromatographic methods, DSC, TGA, DMA, TMA; microscopic techniques or processing methods. 38.- The method according to claim 28, wherein the end-use property that is measured is a mechanical property, a viscoelastic property, a morphological property, an electrical property, an optical property, the permeability to solutes or gases, surface tension or a thermal property. 39.- The method according to claim 28, wherein the end-use property being measured is an antibacterial activity, blood compatibility, tissue compatibility, drug release characteristics, biological interactions with living organisms, hydrolytic degradation or characteristics. of protein adsorption. The method according to claim 28, wherein the end-use property being measured is the polymer processing capacity, radiation stability, sterilization capacity, adhesive properties, hydrophobic characteristics, or specific reaction conditions. . 41- A method for determining the effect of the independent variation of at least two structural characteristics of a condensation-type copolymer in at least one end-use property of said copolymer, comprising; a) measuring at least one end-use property of each copolymer of said copolymer array according to claim 10; and b) comparing the variations in each end-use property measured by each of the mentioned copolymers as a function of the < homologous variation within said series of monomers from which said copolymers were polymerized to determine any relationship between said homologous variations and said variations of end use property between said copoiomers; identifying in this way specific elements of said plurality of copolymers having useful properties for specific end uses. 42. The method according to claim 41, wherein said condensation-type copolymers are prepared by an interface procedure. 43. The method according to claim 41, wherein said condensation-type copolymers are prepared by a suspension process. 44. The method according to claim 41, wherein said copolymers are synthesized in parallel. 45. The method according to claim 41, wherein said condensation type copolymers are poiimerized in solution. 46. The method according to claim 41, wherein said condensation-type copolymers are polymerized by volume. 47. The method according to claim 41, wherein said condensation-type copolymers are polymerized in the presence of a catalyst. 48. The method according to claim 41, wherein said condensation-type copolymers are polymerized in the absence of a catalyst. 49. The method according to claim 41, wherein said polymerizable functional groups of said first series of monomers are amino or hydroxyl groups and said polymerizable functional groups of said additional series of monomers are selected from the group consisting of carboxylic acids, esters, anhydrides and isocyanates. 50. The method according to claim 49, wherein said additional series of monomers comprises second and third series of monomers, said second series of monomers being selected from the group consisting of carboxylic acids, esters, anhydrides and isocyanates, and said The third series of monomers comprises a plurality of alkylene oxides selected from the group consisting of ethylene oxide, propylene oxide, isopropylene oxide, butylene oxide, isobutylene oxide, and random and block polymers and copolymers thereof. 51. The method according to claim 49, wherein said polymerizable functional groups of said first series of monomers are hydroxyl groups and said series of additional monomers comprise a series of monomers with polymerizable carboxylic acid groups. 52. The method according to claim 51, wherein said first series of monomers comprises a plurality of different diphenol compounds, each having the general structure: where Ri is selected from the group consisting of -CH = CH-, (-CH2-) a, and -CHN (L? L2), where a has a value of zero to eight, inclusive, and Li and L2 are they independently select from the group consisting of hydrogen and straight and branched alkyl and alkyl groups containing up to 18 carbon atoms, as long as L1 and L2 are not both hydrogen; b • 10 independently has a value between zero and eight, inclusive; R2 is selected from the group consisting of straight and branched alkyl and alkyl groups containing up to 18 carbon atoms. 53. The method according to claim 51, wherein said first series of monomers comprises a plurality of 15 different aromatic-aliphatic hydroxyl compounds, where each one has the general structure: • wherein R3 is selected from the group consisting of -CH = CH-, (-CH2-) a, and -CHN (L? L2), where a has a value from zero to eight, inclusive, and L1 and L2 are they are independently selected from the group consisting of hydrogen and straight and branched alkyl and alkylaryl groups containing up to 18 carbon atoms, as long as Li and L2 are not both hydrogen; Rs and Re are each independently selected from the group consisting of hydrogen and straight and branched alkyl groups having up to 18 carbon atoms, R4 is (-CH2-) b, wherein b independently has a value between zero and eight, inclusive; R2 is selected from the group consisting of straight and branched alkyaryl and alkyl groups containing up to 18 carbon atoms. 54.- The method according to claim 51, in • wherein said series of monomers with polymerizable carboxylic acid groups comprises a plurality of different dicarboxylic acid compounds, each having the general structure: Wherein R is selected from the group consisting of alkyl, aryl and • Alkylaryl unsaturated and saturated, substituted and unsubstituted containing up to 18 carbon atoms. 55.- The method according to claim 52, in Wherein for one or more of said monomers of said first series of monomers, at least one of L1 or L2 contains at least one ether linkage. 56. The method according to claim 53, wherein for one or more of said monomers of said first series of monomers, at least one of R2, Rs, e, L? or L contains at least one ether link. The method according to claim 54, wherein for one or more of said monomers of said series of dicarboxylic acid monomers R contains at least one ether linkage. 58. The method according to claim 41, wherein said copolymers are further modified by chemical reactions or cross-linking. 59. The method according to claim 41, wherein said end-use properties are measured by ELISA, SAM, chromatographic methods, DSC, TGA, DMA, TMA, microscopic techniques or processing methods. The method according to claim 41, wherein the end-use property that is measured is a mechanical property, viscoelastic property, morphological property, electrical property, optical property, permeability to solutes or gases, surface tension or thermal property. . 61.- The method according to claim 41, wherein the end-use property being measured is an antibacterial activity, blood compatibility, tissue compatibility, drug release characteristics, biological interactions with living organisms, hydrolytic degradation or characteristics. of protein adsorption. 62. - The method according to claim 41, wherein the end-use property to be measured is the polymer processing capacity, the radiation stability, the sterilization capacity, adhesive properties, hydrophobic characteristics or stability under reaction conditions specific. 63.- A polyarylate comprising repetition units that have the structure: wherein R is selected from the group consisting of saturated and unsaturated, substituted and unsubstituted alkyl, aryl and alkylaryl groups containing up to 18 carbon atoms; Ri is selected from the group consisting of -CH = CH-, (-CH2-) a, and -CHN (L? L2), where a has a value of zero to eight, inclusive, and Li and L2 are independently selected from the group consisting of hydrogen and straight and branched alkyl and alkylaryl groups containing up to 18 carbon atoms, as long as Li and L2 are not both hydrogen; b independently has a value between zero and eight, inclusive; and R 'is selected from the group consisting of straight and branched alkyl and alkylaryl groups containing up to 18 carbon atoms; and wherein at least one of R, R2, and, when Ri is -CHNL? L2, Li or L2 contains at least one ether linkage. • The polyarylate according to claim 63, wherein Ri is -CH2-CH2-, b is one and at least not R or R2 contains at least one ether bond. 65. The polyarylate according to claim 64, wherein R2 is selected from the group consisting of hydrogen, ethyl, butyl, hexyl and benzyl and R contains at least one ether linkage. • The polyarylate according to claim 65, wherein R is -CH2-0-CH2- or -CH2-0-CH2-CH2-0-CH2-. 67. The polyarylate according to claim 64, wherein R is selected from the group consisting of -CH2-C (= 0) -, -CH2-CH2-C (= 0) -, -CH = CH- and (-CH -) 2, where z is an integer between 2 and 8, inclusive. 15. The polyarylate according to claim 67, wherein R2 is -CH2-CH2-0-CH2-CH-0-CH2-CH2-OH. • 69.- A diphenolic compound derived from tyrosine that has the structure: where Ri is selected from the group consisting of -CH = CH-, (-CH2-) a, and CHN (L? L2), where a has a value of zero to eight, inclusive, and L? and L2 are independently selected from the group consisting of hydrogen and straight and branched alkyl and alkylaryl groups containing up to 18 atoms • carbon, as long as Li and L2 are not both hydrogen; 5 b independently has a value between zero and eight, inclusive; and R2 is selected from the group consisting of branched and straight alkyl and alkylaryl groups containing up to 18 carbon atoms; and wherein at least one of 2 or, when R1 is -CHNL1L2, U or L2 contains at least one ether linkage. 10 70.- The difeno! according to claim 69, wherein R1 is -CH2-CH-, b is one and R contains at least one ether linkage. 71. The diphenol according to claim 70, wherein R2 is -CH2-CH2-0-CH2-CH2-0-CH2-CH2-OH. 72. The diphenol according to claim 69, wherein Ra is selected from the group consisting of hydrogen, ethyl, butyl, octyl and benzyl, and R1 is -CHNL1L2, wherein at least one of L1 or L2 contains at least one ether link. 73. The diphenol according to claim 72, wherein at least one of L1 or L2 is -CH2-CH2-0-CH2-CH2-0-CH2-CH2-0H. 20 74.- A polyamide ester comprising repeat units containing the structure: 5 wherein R3 is selected from the group consisting of -CH = CH-, (-CH2-) a, and -CHN (L? L2), where a has a value of zero to two, inclusive, and L1 and L2 are independently selected from the group consisting of hydrogen and straight and branched alkyl and alkylaryl groups containing up to 18 atoms F carbon, as long as L1 and L2 are not both hydrogen; R5 and Re are independently selected from the group consisting of hydrogen and straight or branched alkyl groups having up to 18 carbon atoms; R4 is (-CH2-) b, wherein b independently has a value between zero and eight, inclusive; R2 is selected from the group consisting of straight and branched alkyl and alkylaryl groups containing up to 18 carbon atoms; and • R is selected from the group consisting of saturated and unsaturated, substituted and unsubstituted alkyl, aryl and alkylaryl groups containing up to 18 carbon atoms; and where at least one of R, R2, Rs, Re and when R3 is -CHNL? L2¡ or L, contains at least one ether link. 75.- The polyamide ester in accordance with the claim 74, where R3 is (-CH2-) aya is 0, b is one, one of R5 or Re is hydrogen, the other of Rs or Re is a methyl group, and at least one of R or R2 contains at least minus an ether link. 76.- The polyamide ester in accordance with the claim • 75, wherein R is selected from the group consisting of hydrogen, ethyl, butyl, octyl and benzyl and R contains at least one ether linkage. 77.- The polyamide ester in accordance with the claim 76, wherein R is -CH2-0-CH2- or -CH2-O-CH2-CH2-O-CH2-. 78. The polyamide ester according to claim 75, wherein R is selected from the group consisting of -CH2-C (= O) -, -CH2- • 10 CH2-C (= 0) -, -CH = CH- and (-CH2-) Zl where z is an integer between two and eight, inclusive. 79. The polyamide ester according to claim 78, wherein R2 is -CH2-CH2-O-CH2-CH2-O-CH2-CH2-OH. 80.- An aliphatic-aromatic dihydroxy monomer that has the 15 structure: 20 wherein R3 is selected from the group consisting of -CH = CH-, (-CH2-) a, and -CHN (L? L2), where a has a value of zero to two, inclusive, and L1 and L2 are independently selected from the group consisting of hydrogen and straight and branched alkyl and alkylaryl groups containing up to 18 carbon atoms, as long as Li and L2 are not both hydrogen; Rs and Re each are independently selected from the group consisting of hydrogen and straight or branched alkyl groups having up to 18 carbon atoms; R4 is (-CH2-) b, where b independently has a value between zero and eight, inclusive; and R2 is selected from the group consisting of straight and branched alkyl and alkylaryl groups containing up to 18 carbon atoms; and wherein at least one of R2, R5, Re and, when R3 is -CHNL | L2, L1 or L2, contains at least one ether linkage. 81. The dihydroxy compound according to claim 80, wherein R3 is (-CH2-) aya is 0, b is 1, one of R5 or R6 is hydrogen, the other of R5 or Re is a methyl group, and R2 contains at least one ether linkage. 82. The dihydroxy compound according to claim 81, wherein R2 is -CH2-CH2-0-CH2-CH2-0-CH2-CH2-OH.