Synthesis and properties of oligopropylamines with photosensitive o-nitrobenzyl ester core

Abstract

The o-nitrobenzyl ester group is known for more than 50 years as a convenient protecting group and fragment for the design of photosensitive systems, including drug delivery agents. Polymeric amines with these groups are promising systems for medical applications, but the lack of basic knowledge about the possible degradation of these compounds under physiological conditions restrains the development of real preparations. We synthesized five new polyamines with the insertion of the o-nitrobenzyl ester group into the chain, including an oligomeric mixture with a weight average number of amine groups equal to 21. The ester group in the polyamine chain was found to be sensitive to hydrolysis at neutral and alkaline pH values. The presence of an amine group near the ester group facilitates hydrolysis through coordination with a hydroxyl ion or water molecule. The catalytic action of the amine moieties is prevented by protonation of the amine at low pH values or by interaction with polymeric acid. The study of photodegradation of new polyamines by HPLC-MS showed the formation of a number of products, most of which were not considered in previous works with o-nitrobenzyl ester derivatives. The o-nitrobenzyl ester group is used in the design of gene delivery systems and other biomedical preparations as a fragment that can be degraded by light. Our results indicate that photodegradation of o-nitrobenzyl esters can produce a number of compounds whose structure and safety for living organisms must be evaluated before use. On the other hand, the discovered hydrolyzability of o-nitrobenzyl esters catalyzed by a neighboring amine group may find application in the development of drug delivery systems. We have shown that the lifetime of o-nitrobenzyl ester containing polyamines is sufficient for gene delivery. Self-degradation of the delivery agent after penetration into a living cell is a desirable case for the release of the delivered agent.