CE29 - Chimie : analyse, théorie, modélisation

Vibrational Circular Dichroism as a Probe of Non-Covalent Interactions – Dichroprobe

Vibrational Circular Dichroism as a Probe of Non-Covalent Interactions

The Dichroprobe project aims at probing the conformation of flexible chiral molecules, in interaction with a solvent or in the solid, by vibrational circular dichroïsm spectroscopy (VCD). It will combine experiments and the development of unprecedented time-dependent methods resting on polarisable force fields or first-principles molecular dynamics (MD) simulations for the interpretation of VCD spectra.

General objective

The Dichroprobe project aims at developing unprecedented time-dependent methods resting on molecular dynamics (MD) simulations to calculate IR and VCD spectra from the time-correlation functions of the electric and magnetic dipole moments, thus fully accounting for anharmonicity, temperature effects, and environment effects.

Both polarizable force fields and first-principles MD will be validated against experimental measurements of VCD spectra in condensed phases, either in apolar solvent like chloroform, or in polar solvents like DMSO or protic solvents. The dependence of the spectra as a function of temperature will give information on the conformational equilibrium. The spectra obtained by MD will be compared to static methods that approximate the solute-solvent interaction as a small cluster embedded in a solvent treated as a polarizable continuum, in a “cluster-in-a-bulk” approach. Polarizable force fields molecular dynamics simulations will be extended to the solid and supramolecular systems, for which no satisfactory theory has been proposed so far. The spectra simulated thereby will be compared to the experimental spectra. Mode attribution tools will be developed within the frame of the MD simulations for a comprehensive description of the vibrational modes. The experimental work will thus be extended to solid and supramolecular systems.

1) Implementation of the Python ChiPy module suite for trajectory analysis and simulation of VCD spectra by ab initio molecular dynamics.
2) Experimental study of cis and trans 1 amino-2-indanol in DMSO
3) Exploration of the potential energy surfaces of cis and trans 1 amino-2-indanol and their complexes with DMSO.
4) First stage of implementation of the calculation of the magnetic moment by polarizable force fields molecular dynamics.
4) Definition of indicators to classify the different molecular structures obtained

The solid phase experimental spectra will be recorded for the solids of the molecules already studied in solution. We will collect the crystallographic data, either on the databases, or experimentally to have a starting structure for the solid calculations, which will begin in the near future. The implementation of the calculation of the VCD spectra in FFMD is being finalized. The precision of the spectra obtained will depend on the quality of the surfaces of calculated electric and magnetic moments. Comparisons with the surfaces obtained by FPMD are planned. The assignment of the vibration modes of the FFMD spectra will be made by Partner 1 using the tools developed by Partner 4.

International and domestic conferences
1. Talk “Supramolecular Chirality and Vibrational Circular Dichroism based on Molecular Dynamics and Nuclear Velocity Perturbation Theory” by S. Jähnigen at EUCO CTC 2019, Perugia, Italy, 1-5 september 2019
2. «Gas-phase and circular dichroism studies of chiral molecules« Tokyo Institute of Technology Tokyo 12/2019 (Conférence dans un laboratoire, A. Zehnacker)
3. Clustering of Flexible Chiral Molecules: Supersonic Expansion vs. Solid-State spectroscopy.International Symposium Frontiers in Cluster Science: Structure and Dynamics (Technische Universitaet Berlin, 11/ 2019 A. Zehnacker)
4. “Finite temperature vibrational spectra with AMOEBA”. Conférence invitee par C. Clavaguéra. Tinker Developers Meeting Paris 07/2019
5. “Contribution of polarizable force fields to the physicochemical description of the interaction of ions with their environment” Conférence invitee par C. Clavaguéra. ICCSE Hô-Chi Minh City, Vietnam 07/2019
6. 1. Effet du mouvement de puckering et de la formation de liaison hydrogène sur le spectre de dichroïsme circulaire vibrationel d’une molécule flexible : le 1-Indanol. Réunion plénière du GDR 3533 Edifices Moléculaires Isolés et Environnés, Nouan-le-Fuzelier (France) K. Le Barbu-Debus

Vibrational circular dichroism (VCD) is the weak difference in absorption between right- and left-circular polarized infrared light in chiral molecules. Besides its use for determining absolute configurations, VCD is very sensitive to conformational isomerism, molecular interactions or solvation, and thus provides a very sensitive probe of these effects.
However, the quantitative description of VCD spectra of large systems in realistic environments, as it is the case for example for pharmaceutical drugs in aqueous solution, still encounters two major difficulties. On the one hand, flexibility must be taken into account at an acceptable computational cost. On the other hand, the shape of VCD spectra in condensed phase can be strongly altered by molecular interactions with the environment, in particular the solvent. The methods developed so far do not satisfactorily account for these effects. While the sensitivity of VCD spectra to changes in conformational equilibrium can be accounted for by dedicated structure-dependent studies, the sensitivity to specific interactions with the environment is still an unanswered question. A notably complicated case is hydrogen bonding, which possibly modifies the electric and magnetic dipole moments associated with a given vibrational mode, hence the shape of the associated transition in the VCD spectrum.
The Dichroprobe project aims at developing unprecedented time-dependent methods resting on molecular dynamics (MD) simulations to calculate IR and VCD spectra from the time-correlation functions of the electric and magnetic dipole moments, thus fully accounting for anharmonicity, temperature effects, and environment effects. Both polarizable force fields and first-principles MD will be validated against experimental measurements of VCD spectra in condensed phases, either in apolar solvent like chloroform, or in polar solvents like DMSO or protic solvents. The dependence of the spectra as a function of temperature will give information on the conformational equilibrium. The spectra obtained by MD will be compared to static methods that approximate the solute-solvent interaction as a small cluster embedded in a solvent treated as a polarizable continuum, in a “cluster-in-a-bulk” approach. Polarizable force fields molecular dynamics simulations will be extended to the solid and supramolecular systems, for which no satisfactory theory has been proposed so far. The spectra simulated thereby will be compared to the experimental spectra. Mode attribution tools will be developed within the frame of the MD simulations for a comprehensive description of the vibrational modes. This will be of prime importance for clusters and/or the solid in which mode coupling and vibrational exciton splitting are expected to have strong consequences on the shape of the VCD spectra. The experimental work will thus be extended to solid and supramolecular systems.
Besides its fundamental spectroscopic interest, this project will provide invaluable tools for simulating VCD spectra of large flexible systems in realistic environments at an acceptable cost. Developing these new and reliable tools on an open access policy will be beneficial to the broad chemistry and pharmacology communities where chirality is ubiquitous and help promote VCD as an efficient analytical tool.

Project coordinator

Madame Anne Zehnacker (Institut des Sciences Moléculaires d'Orsay)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

LIPHY Laboratoire Interdisciplinaire de Physique
PASTEUR Processus d'Activation Sélectif par Transfert d'Energie Uni-électronique ou Radiatif
LCP Laboratoire de Chimie Physique
ISMO Institut des Sciences Moléculaires d'Orsay

Help of the ANR 389,584 euros
Beginning and duration of the scientific project: September 2018 - 36 Months

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