Interaction of Carboranes with Biomolecules: Formation of Dihydrogen Bonds

Abstract

Noncovalent interactions of the polyhedral carborane 1-carba-closo-dodecaborane (CB(11)H(12))(-) with building blocks of biomolecules, modelled by glycine (GLY), serine (SER), phenylalanine (PHE), glutamic acid (GLU), lysine (LYS) and arginine (ARG), were investigated in vacuo by molecular dynamics simulations with the UFF empirical potential. Selected structures were further studied by accurate ab initio quantum chemical procedures. Interactions with a peptide bond (GLY-SER dipeptide) and a nucleic acid building block (guanine) were also considered. The RESP and NPA charges of carboranes and small model systems are compared and their use is discussed. The dominant interaction between carboranes and biomolecules is the formation of unconventional proton-hydride hydrogen bonds (dihydrogen bonds) characterized by a short distance between hydrogen atoms (as close as 1.8 A) and an average strength in the range of 4.2-5.8 kcal mol(-1). The total stabilization energy of complexes investigated is rather large, and the largest value (approximately 15 kcal mol(-1)) was found for the carborane complexes with ARG and the GLY-SER dipeptide. These interactions are ubiquitous under geometrical constraints influencing the strength of the interaction. The carborane forms dihydrogen bonds with biomolecules preferably with the hydrogen atoms of its lower hemisphere (i.e. the part of the cage opposite to the carbon atom). These two geometrical factors can be used to explain the specificity of inhibition of HIV protease by carboranes.

Nonclassical Hydrophobic Effect in Micellization: Molecular Arrangement of Non‐Amphiphilic Structures

“…This property of boron clusters underlies their capability to form dihydrogen bonds of B-HࢫࢫࢫH-C and other types. [11,12,14] To investigate this possibility, we analyze MD configurations from the deepest free energy minima (cf. Figure 6).…”

“…[14] The two dicarbollide clusters can rotate along the longitudinal axis forming three isomers, i.e., transoid, gauche, and cisoid (Figure 1). In the gas-phase, the transoid rotamer was found to be the most stable, nearly isoenergetic with gauche (+1.6 kJ/mol) and followed by cisoid (+ 10.6 kJ/mol).…”

Metallacarboranes and their interactions: theoretical insights and their applicability

“…As a model for the carborane cages, the [CB 11 H 12 ] -molecule was used and its interactions with model amino acids were investigated in vacuum using DFT and MP2 optimizations and single-point calculations. 41 The formation of dihydrogen bonds and their preferential location in the antipodal part of the cage (B atom opposite to C atom) were rationalized using the calculated RESP atomic charges ( Figure 9). Shifting to larger molecules, a series of substituted metallabisdicarbollides -[3,3'-M-(1,2-C 2 B 9 H 11 ) 2 ] n where M/n stands for Fe/-2, Co/-1 and Ni/0-was treated using a similar methodology but enhanced with an implicit solvent model.…”

“…Comparison of the NPA and the restrained-ESP (RESP) methodologies in the realm of heteroborane interactions showed that only the latter is capable of describing the hydridic nature of the boron-bound hydrogens, which is a prerequisite for the correct description of dihydrogen bonding. 41 The computation of ESP charges is not restricted to biochemical studies of metallacarboranes but also to their use as synergistic agents in the extraction of radionuclide wastes. In this case, the electrostatic potential is fundamental to properly describe these compounds in the simulations at liquid-liquid extraction interfaces with a set of cations.…”

“…52 The nature of the interaction has been rationalized using quantum mechanical calculations as being composed of B-H···H-C dihydrogen bonds (cf. Figure 9) 41 and B-H···Na + interactions. 49 This novel type of binding is the reason for the sustained potency of these metallacarboranes against resistant mutant PRs.…”