Molecular quantum mechanical gradients within the polarizable embedding approach—Application to the internal vibrational Stark shift of acetophenone

Abstract

We present an implementation of analytical quantum mechanical molecular gradients within the polarizable embedding (PE) model to allow for efficient geometry optimizations and vibrational analysis of molecules embedded in large, geometrically frozen environments. We consider a variational ansatz for the quantum region, covering (multiconfigurational) self-consistent-field and Kohn-Sham density functional theory. As the first application of the implementation, we consider the internal vibrational Stark effect of the C==O group of acetophenone in different solvents and derive its vibrational linear Stark tuning rate using harmonic frequencies calculated from analytical gradients and computed local electric fields. Comparisons to PE calculations employing an enlarged quantum region as well as to a non-polarizable embedding scheme show that the inclusion of mutual polarization between acetophenone and water is essential in order to capture the structural modifications and the associated frequency shifts observed in water. For more apolar solvents, a proper description of dispersion and exchange-repulsion becomes increasingly important, and the quality of the optimized structures relies to a larger extent on the quality of the Lennard-Jones parameters. C 2015 AIP Publishing LLC. [http://dx

Vibrational Stark Effects of Carbonyl Probes Applied to Reinterpret IR and Raman Data for Enzyme Inhibitors in Terms of Electric Fields at the Active Site

“…However, we have shown in earlier work 1, 3, 23 and for the compounds discussed here that these frequency shifts can be entirely accounted for by changes in the electric field exerted by different solvents as they interact with the solute oscillator; this treatment explicitly does not alter the physical properties of the solutes, and a recent theoretical analysis by List et al . 7 is consistent with this assumption. Note also that solvent polarity, while convenient and widely used as a description of bulk solvent properties, does not provide a molecular picture and does not even have useful units, in contrast to the electric field.…”

“…16–19 The carbonyl (C=O) vibration, which is generally more intense than nitriles, has been shown to vary linearly with electrostatic field in both H-bonding and non-H-bonding environments. 3, 5, 7–8, 20 The main limitation of the carbonyl probe is that its frequency overlaps with the densely populated amide I region in many biological systems. Fortunately, this can often be overcome by careful selection of a reference sample that is nearly identical to the sample of interest as well as isotopic labeling, or by using Raman spectroscopy.…”

Solvent-Independent Anharmonicity for Carbonyl Oscillators

“…4,7,8 This model assumes that the Stark tuning rate is constant across diverse environments such as in the presence and absence of hydrogen bonding, and this is consistent with vibrational Stark spectroscopy data and MD simulations. 7–9,19,20 …”

“…9,19 Likewise, solution simulations in which the probe bond polarizability was included are also consistent with a linear Stark effect. 20 …”

Averaged Solvent Embedding Potential Parameters for Multiscale Modeling of Molecular Properties

“…We have previously calculated the solvent average electric field at the center of mass of the carbonyl group in solvated acetophenone. 44 The calculated fields were 0.013 a.u. in water, 0.0053 a.u.…”