The Synthesis, Structure and Chemical Reactivity Group develops an interdisciplinary research, which combines the use of experimental techniques and theoretical calculations focused on the synthesis and structural study of a variety of molecules with different properties. The biological activities of some synthesized products are evaluated.
(a) Synthesis, Structural Study and applications of peptide foldamers. The main objectives of this program are the synthesis of new cyclobutyl β- and γ-amino acids and related peptides. Chiral precursors and enzymatic approaches are used to prepare optically active compounds. Solution and solid phase synthesis methodologies are used.
The structural study in solution of the peptides is carried out by using both spectroscopic and chiroptical techniques and X-ray diffraction analysis, combined with molecular modeling.
The ability of cyclobutane oligomers to self-assemble forming nanosized aggregates is under study. The combined use of Transmission Electron Microscopy (TEM), Scanning Electron Microscopy (SEM), Nuclear Magnetic Resonance, together with theoretical calculations allows us the determination of the shape and size of the aggregates as well as the way of self-assembling. In some cases, this aggregation has resulted in the formation of thermoreversible gels with a defined morphology and size. Currently, investigation on various applications of these gels in the fields of Materials Science and Catalysis is ongoing.
(b) Biological activity of cyclobutane and hybrid peptides. In this line of research biological applications of cyclobutane containing peptides are sought. Some recent examples are detailed below.
The combination of lipophilicity and charge density achieved when alternating g-cyclobutane amino acids with conveniently substituted proline residues has made the resulting peptides to be promising non-toxic cell penetrating peptides (CPP). These CPP have been investigated with HeLa cells (cervical cancer cells) and nowadays research is carried out in our laboratory to use them as drug delivery systems and as magnetic resonance imaging (MRI) contrast agents.
Y is one of the most abundant neuropeptides in the central nervous system and is a neurohormone that activates the receptors that are coupled to protein G. The incorporation of some cyclobutane b-amino acids in truncated peptides related to neuropeptide Y (NPY) has resulted in a preferential selectivity for subreceptor Y4.
(c) Chiral polyfunctional cyclobutane containing platforms. Efficient synthetic methodologies have been set to prepare enantiopure cyclobutane derivatives that can act as platforms that are decorated with various functional groups.
Some of these platforms have been used to synthesize surfactants, which are one of the groups of chemicals with most promising applications. A combination of techniques is used to characterize them (cmc determination by the pendant drop method, SAXS, WAXS, TEM,…) Active investigation is currently ongoing in our laboratory to design and tune new surfactants in view of finding applications in various fields (templates for silica-based materials, drug delivery systems,...)
Other interesting applications are being developed using these platforms as scaffolds.
(d) Cyclobutane containing organo- and metalocatalysts. Some of our cyclobutane amino acids and derivatives have been used to prepare bifunctional organocatalysts which have been tested in Michael additions. Some others have been used as ruthenium nanoparticle stabilizers that are used in the hydrogenation of arenes and nitrobenzene derivatives.