“Carboranyl-cysteine”—Synthesis, Structure and Self-Assembly Behavior of a Novel α-Amino Acid

Abstract

Substitution of the thiol proton in cysteine with m-carborane furnished 2-amino-3-(1,7-dicarba-closo-dodecacarboranyl-1-thio)propanoic acid (3), a boron cluster amino acid that exhibits self-assembly to form micron-sized constructs. Field emission scanning electron microscopy revealed that ethanol solutions of 3 form floret-shaped constructs, while fibrillar architectures are formed in water. Furthermore, slow evaporation of methanol solutions of 3 produced crystals whose structure was revealed by X-ray crystallography. The crystal structure shows that the hydrogen bonding interactions between pairs of 3 result in the formation of bilayers of 174 Å in length. The orientation of the clusters is not random in the crystal structure, such that the side-by-side aligned polyhedra are offset by 158 degrees. The material was characterized by FT-IR, NMR, high resolution mass spectrometry and dynamic light scattering. Circular dichroism studies indicated that self-assembly occurs at concentrations as low as 0.01 μM. This represents the first demonstration of self-assembly of a carborane-based molecule in the absence of metals. The amino acid motif provides opportunities for the controlled synthesis of extended multimeric units with tunable properties and the potential for applications in biology, medicine and materials chemistry.

Amino Acid Based Self‐assembled Nanostructures: Complex Structures from Remarkably Simple Building Blocks

“…[22] This modified amino acid formed floret like discs in ethanol and fibers in aqueous solutions. Crystal structures revealed the formation of bilayers via H-bonding interactions.…”

“…Taking a de novo approach, Musah and co-workers synthesized a boron cluster amino acid, 2-amino-3-(1,7-dicarbaclosododecacarboranyl-1-thio)-propanoic acid, by substituting the thiol proton in cysteine with m -carborane. [22] This modified amino acid formed floret like discs in ethanol and fibers in aqueous solutions. Crystal structures revealed the formation of bilayers via H-bonding interactions.…”

On the Aqueous Solution Behavior of C-Substituted 3,1,2-Ruthenadicarbadodecaboranes

“…+20 ppm), analogous to that for complex 3 in DMSO-d 6 , is evident, but no rational behind this was proposed. It was simply concluded by the authors that there is no difference in the NMR spectra between aggregating and "non-aggregating" conditions, although it is not clear why an ethanolic solution should represent "non-aggregating" conditions, since closo-carborane derivatives are also known to form nano-structures in ethanol [27].…”

“…As already mentioned before, aqueous self-assembly of neutral (metalla)carboranes has been so far poorly investigated, and is limited to a few examples of C-substituted closo-carboranes [26,27]. No studies on the effect of spontaneous aggregation on the biological activity profile or stability in the biological medium are found in the literature.…”

Preparing (Metalla)carboranes for Nanomedicine

“…[9,[35][36][37][38][39] In contrast, only a few reports exist which suggest that also non-ionic icosahedral (metalla)carboranes show a tendency to aggregate into nano-and micro-entities in aqueous solutions. [40][41][42][43][44][45][46] However, investigations which translate the physicochemical self-assembling behaviour to the biological concept of colloidal drug aggregates are missing, except our most recent work. [47] Thus, we have shown that neutral boron cluster compounds spontaneously aggregate in buffered solutions and/or in cell culture media.…”