Nitrile and thiocyanate IR probes: molecular dynamics simulation studies.

Nitrile- and thiocyanate-derivatized amino acids have been found to be useful IR probes for investigating their local electrostatic environments in proteins. To shed light on the CN stretch frequency shift and spectral lineshape change induced by interactions with hydrogen-bonding solvent molecules, we carried out both classical and quantum mechanical/molecular mechanical (QM/MM) molecular dynamics (MD) simulations for MeCN and MeSCN in water. These QM/MM and conventional force field MD simulation results were found to be inconsistent with the experimental results as well as with the high-level ab initio calculation results of MeCN-water and MeSCN-water potential energies. Thus, a new set of atomic partial charges of MeCN and MeSCN is obtained. By using the MD simulation trajectories and the electrostatic potential model recently developed, the CN and SCN stretching mode frequency trajectories were obtained and used to simulate the IR spectra. The C[Triple Bond]N frequency blueshifts of MeCN and MeSCN in water are estimated to be 9.0 and 1.9 cm(-1), respectively, in comparison with those of gas phase values. These values are found to be in reasonable agreement with the experimentally measured IR spectra of MeCN, MeSCN, beta-cyano-L-alanine, and cyanylated cysteine in water and other polar solvents.