Nitrile and thiocyanate IR probes: molecular dynamics simulation studies.

Area of Science:

• Physical Chemistry
• Computational Chemistry
• Spectroscopy

Background:

• Nitrile- and thiocyanate-derivatized amino acids serve as infrared (IR) probes for protein local electrostatic environments.
• Understanding solvent interactions with these probes is crucial for interpreting spectral shifts and lineshape changes.

Purpose of the Study:

• To investigate the CN stretch frequency shift and spectral lineshape changes induced by hydrogen-bonding solvent molecules.
• To develop accurate computational models for simulating IR spectra of nitrile- and thiocyanate-containing molecules in solution.

Main Methods:

• Classical and quantum mechanical/molecular mechanical (QM/MM) molecular dynamics (MD) simulations were performed for acetonitrile (MeCN) and methyl thiocyanate (MeSCN) in water.
• A new set of atomic partial charges for MeCN and MeSCN was derived to improve force field accuracy.
• MD simulation trajectories and an electrostatic potential model were used to simulate IR spectra and obtain CN and SCN stretching mode frequency trajectories.

Main Results:

• Initial QM/MM and conventional force field MD simulations showed inconsistencies with experimental and ab initio data.
• The refined atomic partial charges led to improved agreement between simulated and experimental IR spectra.
• Estimated C≡N frequency blueshifts for MeCN and MeSCN in water were 9.0 and 1.9 cm⁻¹, respectively, compared to gas-phase values.

Conclusions:

• The developed computational approach, incorporating refined atomic partial charges, accurately reproduces experimental IR spectra of MeCN and MeSCN in polar solvents.
• This method provides a reliable tool for studying the electrostatic interactions of nitrile- and thiocyanate-containing molecules in biological systems.
• The findings support the use of these probes in understanding protein local environments through IR spectroscopy.