Including Thermal Disorder of Hydrogen Bonding to Describe the Vibrational Circular Dichroism Spectrum of Zwitterionic l-Alanine in Water

Abstract

The vibrational circular dichroism (VCD) spectrum of l-alanine amino acid in aqueous solution in ambient conditions has been studied. The emphasis has been placed on the inclusion of the thermal disorder of the solute-solvent hydrogen bonds that characterize the aqueous solution condition. A combined and sequential use of molecular mechanics and quantum mechanics was adopted. To calculate the average VCD spectrum, the DFT B3LYP/6-311++G(d,p) level of calculation was employed, over one-hundred configurations composed of the solute plus all water molecules making hydrogen bonds with the solute. Simplified considerations including only four explicit solvent molecules and the polarizable continuum model were also made for comparison. Considering the large number of vibration frequencies with only limited experimental results a direct comparison is presented, when possible, and in addition a statistical analysis of the calculated values was performed. The results are found to be in line with the experiment, leading to the conclusion that including thermal disorder may improve the agreement of the vibrational frequencies with experimental results, but the thermal effects may be of greater value in the calculations of the rotational strengths.

Effective Fully Polarizable QM/MM Approach To Model Vibrational Circular Dichroism Spectra of Systems in Aqueous Solution

“…This is the smallest chiral amino acid and as the others occurs in the zwitterionic form in aqueous solution, that is its natural environment. The VCD spectrum of ( l )-ALA in aqueous solution has been studied both from a theoretical and an experimental point of view, and it was the first system for which vibrational optical activity techniques were applied. − However, to the best of our knowledge, this is the first time that the VCD spectrum of this molecule is studied by the combination of classical MD and a QM/MM approaches.…”

Classical Magnetic Dipole Moments for the Simulation of Vibrational Circular Dichroism by ab Initio Molecular Dynamics

“…To reproduce experimental conditions, it is often necessary to include the influence of the molecular surrounding in the bulk phase or in a solution. In the context of static quantum chemistry, this is possible by implicit solvation models and microsolvation approaches with explicit solvent molecules, as has been done, for example, to study the VCD spectra of several biomolecules. − Such solute–solvent clusters can be extracted from molecular dynamics (MD) simulations, , but it would be desirable to directly employ MD without modifications of the molecular surrounding to capture the dynamic nature of the intermolecular interaction network and to cover the conformational flexibility in the bulk phase.…”

Competition between inter and intramolecular hydrogen bond evidenced by vibrational circular dichroism spectroscopy: The case of (1S,2R)‐(−)‐cis‐1‐amino‐2‐indanol

“…32 Molecular dynamics approaches have been proposed to account for these effects, which rest either on force fields or on first-principle simulations. [33][34][35][36][37] However, they are often computationally demanding, in particular for complex or large molecules. An efficient alternative has been proposed, which consists in approximating the solute/solvent system by a limited number of clusters of well-defined size and shape, embedded in a solvent continuum.…”

“…This aspect is especially important for simulating the VCD spectrum of hydroxyl‐containing molecules, whose OH bend region is very sensitive to structural dynamics 32 . Molecular dynamics approaches have been proposed to account for these effects, which rest either on force fields or on first‐principle simulations 33–37 . However, they are often computationally demanding, in particular for complex or large molecules.…”