Trimethyl Lock - A Multifunctional Molecular Tool for Drug Delivery, Cellular Imaging and Stimuli-responsive Materials.

Trimethyl lock (TML) systems are based on ortho-hydroxy dihydro cinnamic acid derivatives displaying an increased lactonization reactivity due to unfavorable steric interactions of three pendant methyl groups leading to the formation of hydro coumarins. Protection of the phenolic hydroxy function or masking of the reactivity as benzoquinone derivatives prevents lactonization and provides a trigger for controlled release of molecules attached to the carboxylic acid function via amides, esters or thioesters. Their easy synthesis and possible chemical adaption to several different triggers make TMLs a highly versatile module for the development of drug delivery systems, prodrug approaches, cell imaging tools, molecular tools for supramolecular chemistry as well as smart stimuli-responsive materials.