Diseño de moléculas con actividad biológicasíntesis e implicaciones en química supramolecular

Abstract

One of the great challenges in Supramolecular Chemistry is the imitation of the behaviour of biomolecules. For this, the design of synthetic compounds that have great affinity and selectivity between them (hosts and guests) is necessary. In this discipline, molecular recognition for the formation of complexes by noncovalent bonds establishes the basis of host-guest chemistry. Cucurbit[n]urils are macrocycles with high structural rigidity that can form supramolecular complexes in aqueous solution with higher affinity and selectivity than other hosts. Thus, they are able to bind guests with different structures, functional groups and charge status. Besides, their low toxicity makes them really interesting for the control of biological processes, drug delivery, modification of biomolecules, amongst other biological applications. In this doctoral thesis, the strategy to be followed includes both the characterization and the design and development of systems for the light-activated supramolecular release of biological guests from their cucurbit[n]uril complexes in water. For this purpose, a photoactive compound is used whose entry into the macrocycle is initially prevented and after being irradiated generates a competing species that displaces the guest from the cavity. The first of the systems presented in this work consists of the use of a protected competitor that in the first instance contains a photosensitive protective group for the light-induced release of terpenic natural products from CB7. Next, another procedure is described for the displacement of a tripeptide from its ternary complex with CB8 by means of a chalcone/flavylium photoswitch that is activated with two inputs (light and acid). Finally, a system for the release of aminoacids and neurotransmitters from the SCX4 host (highly soluble in aqueous medium) was developed. The latter works by means of competition of a flavylium cation, showing the reversibility of the system. Generally, supramolecular systems including synthetic hosts for light-controlled delivery of species of interest in biological conditions have been characterized and improved.