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. Author manuscript; available in PMC: 2015 Jan 28.
Published in final edited form as: J Control Release. 2013 Nov 12;174:88–97. doi: 10.1016/j.jconrel.2013.11.003

Scheme 4.

Scheme 4

The proposed mechanism for reversible, pH dependent ring opening of TPT from its lactone, L, to carboxylate, CCOO-, form. Because ring opening proceeds through the carboxylic acid species, CCOOH, ring opening increases as more carboxylate is formed at higher pH, as governed by the acid dissociation constant for the E-ring carboxylic acid, KCOOH.