Interaction of carboranes with biomolecules:: Formation of dihydrogen bonds

Noncovalent interactions of the polyhedral corborone 1-corbacloso-dodecaborone (CB11H12)(-) with building blocks of biomolecules, modelled by glycine (GLY), serine (SER), phenylalanine (PHE), glutamic acid (GLU), lysine (LYS) and arginine (ARG), were investigated in vacua by molecular dynamics simulations with the UFF empirical potential. Selected structures were further studied by accurate ob 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 angstrom) and on 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 (approximate to 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 carborones.