CN101580506A - 1-3 generation arylene ether dendritic phthalocyanine complex and polymer nano-particle thereof - Google Patents

Abstract

The invention discloses a 1-3 generation arylene ether-substituted dendritic phthalocyanine zinc complex, a preparation method and an application thereof. The method comprises the following steps of adopting a Frechet synthesis method to synthesize the first to third generation alcohol molecules which take the 1-3 generation cyan as an end group; leading the first to third generation alcohols to react with 4-nitrophthalonitrile respectively, thus synthesizing corresponding phthalocyanine precursor of dendrimer taking the 1-3 generation cyan as the end group; subsequently, leading the phthalocyanine precursor ring of dendrimer taking the 1-3 generation cyan as the end group to synthesize corresponding arylene ether dendritic phthalocyanine taking the first to third generation cyan as the end group and the arylene ether dendritic phthalocyanine taking the first to third generation carboxyl as the end group generated by hydrolysis. The 1-3 generation arylene ether dendritic phthalocyanine complex and the amphiphilic block copolymer are automatically dissolved to form the polymer nano-particle loading the 1-3 generation arylene ether dendritic phthalocyanine complex. The 1-3 generation diaryl ether dendritic phthalocyanine zinc complex and the loaded polymer nano-particle thereof are used as photosencitizers for photodynamic therapy.

Description

1-3 is for aryl oxide dendritic phthalocyanine complex and polymer nano-particle thereof

Technical field:

The invention belongs to the title complex field, especially belong to a kind of 1-3 for aryl oxide dendritic phthalocyanine Zn complex and polymer nano-particle and preparation method, this title complex is applied to optical dynamic therapy moist macular degeneration class disease and cancer as photosensitizers.

Background technology:

(photodynamic therapy PDT) is a kind of treatment cancer to photodynamic therapy, the novel method of HIV and moist macular degeneration class disease.The key of optical dynamic therapy is a photosensitizers.Phthalocyanine complex is because of having the skeleton structure similar to haematoporphyrin, the more stable and easy modification of structure, and maximum absorption wavelength is positioned at about 670nm, easily sees through the ruddiness zone of tissue and can make pure product, is considered to the very potential photosensitizers of a class.Because the intermolecular intensive π of phthalocyanine-π effect is assembled easily, thereby reduce the fluorescence quantum yield of molecule, shorten the triplet state quantum life-span, thereby reduce photosensitization efficient.Therefore, be difficult for the goal in research that the accumulative photosensitizers is for we between the design synthetic molecules.

Dendritic polymer (dendrimer) is the novel cpd that the class that grows up nearly decades has special construction.This hyperbranched polymer with exquisite structure had caused scientist's attention immediately after people such as Tomalia and Newkome successfully synthesize first kind dendritic polymer first in 1985.Branch type polymkeric substance is made of three parts, i.e. core, branching unit and peripheral functional group.Be characterized in compound with regular structure, controlledly synthesis, molecular scale is at nano level, and the internal cavity can comprise various molecules.Along with the growth of periphery functional group algebraically, functional group's number is exponential growth to the periphery from core.The functional group surface can be made into the close quarters of being made up of the differing molecular group.These molecular radicals can play the effect of hook, can combine with the multivalent molecule attachment point of virus and cell surface, thereby are used to adhere to various useful molecules.In addition, three-dimensional branch macromole is a non-biological material, can not bring out patient's immune response, so select the carrier of branch macromole as medicine, carrying and carry medicine to enter blood of human body circulation and be transported to diseased region, reach therapeutic purpose, is the development trend of Nano medication.Appearing in the newspapers with the phthalocyanine complex with optical dynamic therapy effect abroad is nuclear, surrounds only 5 classes of the macromolecular dendroid photosensitizers of branch on every side.Julien L.D etc. are by synthetic eight replacements of the method for dispersing 5 generation phosphorus hydrazine dendriform metal-free phthalocyanine.MutsumiKimura etc. replace polyethers-amino dendritic phthalocyanine zinc by the method for dispersing synthetic four.Mutsumi Kimura etc. have also synthesized four replacements by the method for dispersing and have contained the dendritic phthalocyanine cobalt of Behera ammonia.Casey A. etc. are by synthetic eight replacements of convergent synthesis 3 generation poly alkyl ether metal-free phthalocyanine.Dennis K.P.Ng is by the synthetic ester class end group four replacements 3 generation polyarylether Phthalocyanine Zinc that has of convergent synthesis.Result of study shows: compare with traditional phthalocyanine complex, these are nuclear with the phthalocyanine complex, and three-dimensional branch macromole is that substituent photosensitizers has the following advantages: along with periphery functional group algebraically increases, effectively penetrating wavelength increases; Because big sterically hindered of periphery functional group has the site centrifugation to phthalocyanine nucleus, cause phthalocyanine under high density, also to be difficult for forming aggregate, and the high point of the quantum yield of singlet oxygen.Yet there are no both at home and abroad with the end group is the report of the 1-3 of carboxyl and cyano group for the aryl oxide dendritic phthalocyanine complex.

Also have, all there is a common weakness in described phthalocyanine complex as the photosensitizers of the s-generation, and uptake ratio and inrichment in the cambium are lower.And the 3rd generation photosensitizers be the 2nd generation p