ITVE20070041A1 - CHEMICAL GAS SENSOR AND METHOD FOR ITS REALIZATION. - Google Patents

Description

DESCRIPTION

of the invention entitled:

"Chemical sensor for gas and method for its realization" The present invention relates to a chemical sensor for gas and a method for its realization.

From the patent application RM2005A000082 the use of self-assembly techniques of organic molecules on monocrystalline silicon surfaces is known to create devices capable of detecting gaseous mixtures, exploiting the supramolecular interactions between the molecular fragment attached to the surface (hereinafter indicated as a "receptor molecule") and the gaseous molecules, with which the surface comes into contact. These devices (hereinafter referred to as "molecular sensors") are based on the modulation of the electric field induced by the supramolecular interaction between the gas molecule and the receptor molecule at the interface between a metal layer and a semiconductor material, and allow detection of the gaseous mixture by measuring the variation of an electrical characteristic of said interface.

Also from the same patent application RM2005A000083 is also known a specific class of receptor molecules suitable for the selective detection of aromatic nitro-derivatives.

Polymeric, synthetic and natural materials are also known, which have found wide application in the chemical modification of electrodes. Among these, cyclodextrins have been intensively studied for their ability to form inclusion complexes with many organic and inorganic molecules of suitable size (Ferancovà, A. and Labuda, J. "Cyclodextrins as electrode modifiers", Fresenius' Journal of Analytical Chemistry, 370 (2001) 1-10.). In these systems, the complexation is driven by non-covalent interactions and is therefore reversible, and leads to the encapsulation of the host particles in the oligosaccharide cavity. The coupling of the cyclodextrins can be obtained through known techniques for the formation of self-assembled monolayers, polymeric films or through known procedures for incorporation into elastic membranes or composite materials (gels, carbon-based pastes, eco).

The use of long and flexible aliphatic chains (called "spacers") is commonly considered essential in order to allow the covalent coupling of large molecules (such as cyclodextrins) to surfaces of crystalline solids. However, this need is in contrast with the use of any molecule as a receptor molecule in the chemical sensors for gases described in the aforementioned patent application RM2005A000082. In fact, the presence of "spacers" introduces conformational degrees of freedom in the molecule attached to the surface, and these lead to the cancellation of the average additional electric field induced by the formation of the supramolecular complex between said molecule and the gas molecule.

According to the invention, the problem is solved with a chemical sensor for gas comprising a layer of conductive material, a layer of organic molecules covalently bonded to the surface of the semiconductor layer with a direct carbon-atom bond on the surface of the semiconductor, and a layer of material porous, characterized in that the layer of organic molecules comprises cyclodextrin derivatives.

Still according to the invention, to create the sensor, the surface of the semiconductor is activated by coupling the surface of the semiconductor with a covalent carbonatom bond, of a material intended to react with cyclodextrin derivatives.

The present invention is further clarified hereinafter in its general characteristics and in some examples of practical embodiment given purely by way of non-limiting example with reference to the attached drawings, in which:

Figure 1 shows the structural formula and its conventional general representation of β-cyclodextrin monoazide,

Figure 2 shows the structural formula and its conventional general representation of β-cyclodextrin monoamine,

Figure 3 shows the general representation of the different cyclodextrins attached to the surface of the semiconductor,

Figure 4 shows the β-cyclodextrin monoazide attached to the surface of the semiconductor,

Figure 5 shows the β-cyclodextrin monoamine attached to the surface of the semiconductor,

Figure 6 shows a comparison between the electrical responses of a molecular sensor functionalized with benzoic acid, according to the state of the art, and with βcyclodextrin, according to the invention, to the introduction of paranitrotoluene vapors (0.13% vol.).

With reference to the drawings, the molecular sensor according to the invention uses a synthesis methodology that does not introduce conformational degrees of freedom in the cyclodextrin attached to the semiconductor surface, since it does not use conventional spacers, but small rigid fragments, such as triazoles or acid amides. self-sustaining benzoics. This result is achieved starting from a common cyclodextrin intermediate, typified by the β-cyclodextrin monoazide of fig. 1, with a two-step sequence: in the first the surface is functionalized with acetylene or with self-sustaining benzoic acids, in the second the coupling of β-cyclodextrin monoazide or its derivative β-cyclodextrin monoamine is achieved.

A method for the non-oxidative functionalization of silicon (111) single crystals with benzoquinones is known from the scientific literature, which proceeds in two steps: a surface acetylenation reaction followed by a Cu-catalyzed Huisgen cycloaddition reaction of an azide on the alkyne bonded to the silicon surface (Rohde, R.D., Agnew, H.D. et al. "A Non-Oxidative Approach toward Chemically and Electrochemically Functionalizing Si (111)", J. Am. Chem. Soc., 128 (2006) 9518- 9525.). This methodical note, so far applied only to small molecules, can be successfully used for the direct attachment to the silicon surface even of highly bulky molecules such as cyclodextrins. According to the invention, the Si surface is thoroughly ethinylated and a protected or unprotected α- or β- or γ-cyclodextrin monoazide is attached to it (general formula 1 in figures 1 and 2) using a copper catalyst. Upon binding to the acetylene residue on the surface, the azide group transforms into a triazole. The surface is then functionalized with a residue of general structure triazol-4-cyclodextrin (general formula 2, figure 2). Alternatively, the cyclodextrin derivative 2 was hooked directly to the monocrystalline silicon surfaces by forming an amide bond. In both cases, the organic layer thus obtained by forming Si-C covalent bonds has a high degree of stability and is rigidly integral with the silicon surface.

Silicon surfaces on which cyclodextrins have been anchored with the method described here can be usefully used in the production of chemical sensors for gases. The advantages deriving from the availability of sensors thus functionalized are varied and remarkable. Figure 6 comparatively shows the electrical response of a "molecular sensor" that uses a βcyclodextrin as a receptor molecule and of a "molecular sensor" that uses benzoic acid as a receptor molecule, to the introduction of para-nitrotoluene. The experimental data show how the use of cyclodextrins rigidly attached to a silicon surface allows the detection of gaseous molecules with a significantly higher response than that recorded in the case of aromatic fragments attached to the surface.

The realization of a molecular sensor according to the invention first involves the synthesis of monoazide cyclodextrins and paracetylated monoamine and subsequently their coupling to the surface of the previously functionalized semiconductor.

The preparation of the cyclodextrins to be coupled is exemplified for the case of β-cyclodextrin (CD) monoazide (figure 1, 1, n = 7, R = H), of peracetylated monoazide (figure 1, 1, n = 7, R = Ac ) and peracetylated β-cyclodextrin (CD) monoamine (figure 1, 2, n = 7, R = H). The synthetic sequence is illustrated in Scheme 1:

Scheme 1. Synthesis of cyclodextrin derivatives used for the coupling reactions

Synthesis of monosylated β-CD 3. Monotosylate 3 was prepared according to Bausanne, I. et al, Chem. Comm. 2000, 1489-1490

CuS04 * 5H20 (7.5 g, 30 mmol, 3 eq., PM = 249.68 g / mol) in distilled water (750 ml), and subsequently 1M NaOH (10 g, 250 mmol, 25 eq., MW = 40 g / mol).

After ten minutes, a solution of p-toluenesulfonyl-Cl (15.01 g, 79 mmol, 7.9 eq., MW = 190 g / mol) in CH3CN (100 ml) in CH3CN (100 ml) begins to drop into this solution over an hour. The reaction is left under magnetic stirring for 5 hours at room temperature. The solution is neutralized by adding 1M HCl (50 ml) and the copper salts are filtered on a celite bed. The solution is lyophilized for one third of the volume and the remaining solid is filtered, recrystallized twice from water, washed twice with acetone (40 ml) and then with ethyl ether (30 ml); then dried under vacuum. Yield: 48% (6.2 g)

Synthesis of β-CD monoazide 1 (n = 7, R = H) Reference: Jicsinszky I., Ivanyi R., Carbohydr. Polym., 2001, 45, 139-145.

Monotosylated β-CD (1 g, 0.77 mmol, 1 eq., MW = 1288.53 g / mol) is dissolved in anhydrous DMF (7 ml) and NaN3 (60 mg, 0.925 mmol, 1.2 eq., PM = 65 g) is added. / mol) under magnetic stirring. It is left to react under nitrogen for 1 hour at 110 ° C, then it is allowed to cool and the product is precipitated from acetone twice, filtered and dried under vacuum. Yield: 90-95% (800-830 mg)

Synthesis of peracetylated β -CD monoazide 1 (n = 7, R = Ac) References: Yin-Fun Poon, I. W. Muderawan, Siu-Choon Ng, J.of Chrom. A, 2006, 1101, 185-197.

To a solution of β-CD monoazide (1.5 g, 1.3 mmol, 1 eq., MW = 1160 g / mol) in anhydrous pyridine (21 ml), under nitrogen flow and magnetic stirring, acetic anhydride (5 ml ) and it is left to react overnight at 60 ° C. At the end, the pyridine is evaporated completely in rotavapor, distilled water and 10% HCI are added up to pH 5 and extracted with ethyl acetate. The organic phase is dried with Na2SO4, filtered and dried in a rotavapor. Yield: quantitative (2.60 g)

Synthesis of peracetylated β -CD monoamine 2 (n = 7, R = Ac)

The peracetylated β-CD monoazide (2.6 g, 1.3 mmol, 1 eq., MW = 2000 g / mol) is dissolved in MeOH dry (13 ml) in the special glass cylinder to be inserted in the autoclave, a spatula tip is added. of catalyst (Pd / C 10% wt., Aldrich 330108-10G), it is left to react in an autoclave, at room T and 80 psi (about 4 atm) for one night at room temperature. At the end of the reduction, it is filtered on celite and the MeOH is evaporated. The product is redissolved cold in CH2CI2o MeOH and decanted with the help of a Pasteur, to eliminate the catalyst. Further traces of metal can be eliminated by filtering the solution in cold MeOH through a syringe with an HPLC filter (45 µm porosity).

Yield: 90%

Once the β-CD monoazide or pre-acetylated monoamine has been obtained, its attachment to the surface of the semiconductor, consisting for example of silicon (111) provides for the preventive functionalization of its surface.

Attachment of acetylenes and subsequent immobilization of β-CD to the Si (111) surface by Huisgen cycloaddition

This functionalization is carried out on a p-type Si (111) sample, 8-12 ohm * cm. The silicon surface is subjected to a cleaning treatment from organic residues consisting of two washes in trichlorethylene for 10 minutes under ultrasonic stirring and two washes in acetone for 10 minutes. under ultrasonic stirring. Subsequently the sample is rinsed for 1 min in bidistilled H20O, and then it is subjected to (1) treatment in an aqueous solution containing hydrogen peroxide and hydrochloric acid at 90 ° C for 20 min; (2) rinsing for 1 min in bidistilled H20; (3) treatment in aqueous solution of 40% NH4F for 5 min. in the dark under the flow of Ar; (4) rinse in double distilled H20 for 1 min. The sample is then transferred to a reactor for the surface activation reaction in the presence of a small amount of benzoyl peroxide. The reaction environment is constantly maintained under nitrogen and all the glassware previously dried in a stove for one night at 120 ° C. Separately, 230 mg of PCI5 in 4 ml of anhydrous chlorobenzene (supersaturated solution with bottom body) are dissolved under magnetic stirring in a reaction flask. After a few minutes of stirring, the supernatant solution is transferred to the reactor where the sample was placed and left to react for 1 hour at 90 ° C under stirring. After this time, the solution is removed and the sample is rinsed with three washes in anhydrous chlorobenzene. The coupling reaction of the acetylene fragment takes place in the same reactor, introducing a quantity of sodium acetylide 18% w / w in xylene and mineral oil sufficient to completely cover the sample. After one night at 130 ° C the solution is removed and the sample rinsed three times with anhydrous tetrahydrofuran. Subsequently, 200 mg of the peracetylated β-CD monoazide are introduced into the reactor together with the sample. Separately, a 3.4 mM solution of sodium ascorbate in dimethylformamide and an 11.6 mM of copper sulphate pentahydrate in dimethylformamide are prepared. 0.75 ml of the first solution are taken and as many of the second solution are introduced into the reactor. It is made up to the mark with another 1.5 ml of dimethylformamide and is left to react overnight. At the end of the foreseen time the solution is removed and the sample is washed three times with dimethylformamide, twice with CH2CI2, twice with methanol and finally left for 10 min in methanol under ultrasonic stirring.

Attachment of benzoic acid and subsequent immobilization of β-CD to the Si (100) surface through the formation of an amide

The functionalization of the surface is carried out on a sample of Si (100) of type p, 8-12 ohm * cm. The silicon surface is subjected to a cleaning treatment from organic residues and metal contaminations called RCA consisting of a washing in trichlorethylene for 10 minutes at a temperature of about 80 ° C followed by a washing in acetone for 10 minutes at a temperature of about 50 ° C and final rinse in cold distilled water, stirring. The following treatments are then carried out: (a) APM attack (NH3 (32% vol.): H2O2 (30% vol.): H20 = 1: 1: 5) for 10 minutes at a temperature of about 80 ° C; (b) washing for 2 minutes, cold and stirring in bidistilled H20; (c) treatment in DHF (Diluited Hydrofluoric Acid; HF (50% vol.): ΗΙ20 = 1:50) for 30 seconds with cold shaking; (d) washing for 2 minutes, cold and stirring in bidistilled ΗΙ20; (e) treatment in HPM (HCI (37%): H2O2 (30%): H20 = 1: 1: 5) for 10 minutes at a temperature of about 80 ° C; (f) treatment in DFIF for 30 seconds with cold shaking and rinsing with ΗΙ20 bidistilled; (g) washing for 2 minutes, cold and shaking in ΗΙ20 bidistilled. The final surface is hydrogenated and ready for the self-assembly reaction. The sample thus prepared is placed in a previously anhydrified reactor and maintained in a nitrogen atmosphere. A metallorganic catalyst (Ru (CO) HCI (PPh3) 3) and the benzyl ester of 4-ethinylbenzoic acid in a 0.1 mmol: 2 mmol ratio are added using anhydrous CH2CI2 as solvent. The reaction proceeds under stirring, at room temperature, in an inert atmosphere and for 15 hours. Subsequently the solution is removed and the sample washed three times with anhydrous CH2CI2 and sonicated for 5 minutes in this same solvent. The self-assembled monolayer of benzyl ester is transformed into the corresponding acid by means of a treatment in TFA (trifluoroacetic acid) 6M in CH2CI2 for 5 days, followed by 3 washes in anhydrous CH2CI2 and sonication for 5 minutes in the same solvent.

The functionalized surface is activated via chloride or mixed anhydride.

For activation via chloride, the silicon prism is placed under nitrogen in a special glass reactor capped with a silicone septum and the air is purged with a needle inserted in the silicone septum. After 15 minutes anhydrous Toluene (1.5 ml) is added as solvent and triethylamine (20 μΙ, 0.143 mmol, d = 0.726 g / ml, MW = 101.19 g / mol), sonicated for one minute to ensure the mixing of the solution and then SOCI2 (3 ml, 15.46 mmoles, d = 1.631 g / ml, MW = 118.97 g / mol) is added. The reaction is sonicated at 40 ° C for 30 minutes. The prism is removed, washed abundantly, sonicating with anhydrous Toluene. The peracetylated β-CD monoamine (1.3 g, 0.65 mmoles, MW = 1974 g / mol), kept overnight in an oven at 100 ° C, is dissolved in toluene (4 + 2 ml) in a flask; then transferred with a syringe into the reactor containing the prism, and triethylamine (20 μΙ, 0.143 mmol, d = 0.726 g / ml, MW = 101.19 g / mol). The reaction is maintained under stirring using a tilting plate for 84 hours. A washing cycle is then carried out in toluene-CH2CI2-THF-H2O 1: 1.

For activation via mixed anhydride, the silicon prism is placed under nitrogen in a special glass reactor capped with a silicone septum and the air is purged with a needle inserted in the silicone septum. After 15 minutes anhydrous THF (4 ml) is added as solvent and N-methyl morpholine (3.3 μΙ, 0.03 mmol, d = 0.92 g / ml, MW = 101 g / mol), sonicated for one minute to ensure mixing. of the solution and then isobutyl chloroformate is added (1.3 μΙ, 0.01 mmol, d = 1.04 g / ml, MW = 136.58 g / mol). The reaction is sonicated at 40 ° C for 1 hour. The prism is removed, washed abundantly, sonicating with anhydrous THF.

The peracetylated β-CD monoamine (300 mg, 0.14 mmoles, MW = 1974 g / mol), kept overnight in an oven at 100 ° C, is dissolved in THF (4 ml) in a flask; then transferred with a dry syringe into the reactor containing the prism. For the following four hours the reaction is sonicated, and for another 40 hours it is kept under stirring using a tilting plate. The prism is then subjected to a wash cycle in THF, H20, CH2CI2.

The present invention has been illustrated and described in its general principles and in some practical examples of embodiment, but it is understood that executive variations may in practice be applied to it without however departing from the scope of protection of the present patent for industrial invention.

Claims (19)

R I V E N D I C A Z I 0 N I 1. Chemical sensor for gas comprising a layer of semiconductor material, a layer of organic molecules covalently bonded to the surface of the semiconductor layer with a direct carbon-atom bond of the semiconductor surface, and a porous metal layer, characterized in that the layer of organic molecules includes derivatives of cyclodextrins. 2. Sensor according to claim 1 characterized in that the semiconductor material consists of silicon. 3. Sensor according to claim 2 characterized in that the semiconductor material consists of monocrystalline silicon. 4. Sensor according to claim 1 characterized in that the cyclodextrins of the organic molecule layer is bound to the semiconductor material layer by means of triazoles. 5. Sensor according to claim 1 characterized in that the cyclodextrins of the organic molecule layer is bound to the semiconductor material layer by self-sustaining aromatic amides. 6. Sensor according to claim 1 characterized in that the hydroxyl groups of the cyclodextrin derivatives are at least partially functionalized as ethers. 7. Sensor according to claim 1 characterized in that the hydroxyl groups of the cyclodextrin derivatives are at least partially functionalized as esters. 8. Sensor according to claim 1 characterized in that the hydroxy groups of the cyclodextrin derivatives are at least partially replaced by amino groups. 9. Sensor according to claim 1 characterized in that the hydroxy groups of the cyclodextrin derivatives are at least partially replaced by nitro groups. 10. Sensor according to claim 1 characterized in that the cyclodextrins consist of β-cyclodextrins. 11. Method for manufacturing a chemical sensor for gas according to one or more of claims 1 to 10, characterized in that the surface of the semiconductor is activated by coupling, with a carbon-atom covalent bond of the surface of the semiconductor, of molecules intended to react with cyclodextrin derivatives. 12. Method according to claim 11 characterized in that the surface of the semiconductor is activated with self-sustaining aromatic molecules containing carboxylic groups. 13. Method according to claim 11 characterized in that the surface of the semiconductor is activated with self-sustaining molecules containing carboxylic groups in a para position with respect to a vinyl group directly bonded to an atom of the surface of the semiconductor. 14. Method according to claim 11 characterized in that the surface of the semiconductor is activated with acetylene directly bonded to an atom of the surface of the semiconductor. 15. Method according to claims 12 and 13 characterized in that the amidation of at least one carboxylic group is carried out with an amine of the cyclodextrin or its derivatives. 16. Method according to claim 15 characterized in that the monoamine of the cyclodextrin or its derivatives is used. 17. Method according to claim 14 characterized in that the synthesis of triazole is carried out by cycloaddition of acetylene with an azide of cyclodextrin or its derivatives. 18. Method according to claim 17 characterized in that the synthesis of triazole is carried out by cycloaddition of acetylene with the monoazide of cyclodextrin or its derivatives. 19. Chemical sensor for gas according to claims 1 to 10 and method for its realization according to claims 11 to 18 and substantially as illustrated and described.