New atomistic model of pyrrole with improved liquid state properties and structure

Abstract

Structural characterization of liquid pyrrole has been obtained by performing classical molecular dynamics simulations with a new parameterization of electrostatic interactions. Despite the relatively simple molecular structure of pyrrole, a correct and accurate representation of its intermolecular interactions in bulk phase is a challenging task, since these are affected at short range by the quadrupole-quadrupole term. This new parameterization permits not only to correctly describe the liquid structure but also to obtain macroscopic properties in excellent agreement with experiments.bulk properties, force field, molecular dynamics, quadrupole moment 1 | I N TR ODU C TI ON Pyrrole (C 4 H 5 N) is one of the simplest and most representative heteroaromatic molecules. Its five-membered ring is the building block of several molecules of biological and pharmacological relevance, such as amino acids, indole alkaloids, [1] and porphyrins. [2] Some molecules containing the pyrrole moiety find application also as therapeutic compounds like fungicides, antibiotics, anti-inflammatory drugs, [3] cholesterol reducing drugs, [4] and antitumor agents. [5] Pyrrole has been used in technological applications like, for example, polymers with remarkable electric conductivity [6] and in dye-sensitized solar cells. [7,8] The structure of pyrrole (see Figure 1) features an NAH group and a p system, which permit effective self-aggregation into clusters through the formation of a weak NAHÁ Á Á p hydrogen bonds. This behavior has been confirmed by experimental and theoretical studies which have shown the tendency to form T-shaped aggregates, [9][10][11][12][13] which are typical structures found in the so called "quadrupolar crystals". In particular, it has been observed in microwave spectroscopy experiments [14] that the angle formed by two monomers approaches to $55 with a distance between the centers of mass of $4:1 Å.The nature of the NAHÁ Á Á p hydrogen bond and the relevance of high multipole contributions to the liquid structure are not yet completely understood, especially in the liquid state. In fact, although several studies about small clusters are available, only few experimental and theoretical studies have been performed on liquid pyrrole. [13,[15][16][17] Hence, in this work, we present a computational study on liquid pyrrole with the purpose of accurately determining its structural features and bulk properties.The structure of liquid pyrrole and its evolution over time has been described by classical molecular dynamics (MD), which allows to estimate macroscopic properties from microscopic models. To obtain results comparable with experiments, it is mandatory to employ an accurate force field (FF), which describes the interactions at atomic and molecular level using a set of functional forms based on a limited number of parameters. Some properties are very sensitive to the electrostatic part of the force field, which in the most widely used FFs is described using partial atomic charges.Int J Quantum Chem. 2018;118:e25554.

Simulating Absorption Spectra of Flavonoids in Aqueous Solution: A Polarizable QM/MM Study

“…In particular, MD production runs were carried out for each of the four molecules for a time long enough to obtain an accurate sampling of the phase space, in order to correctly reproduce all possible system configurations and their relative energy. In order to recover the directionality of hydrogen bonding (HB) interactions, we also placed off-site charges (the so-called virtual sites (VS) or dummy atoms) to better describe the lone pairs of the Oxygen atom (see Figure 2 for a graphical representation) [ 44 , 65 , 66 ]. Therefore, two different classical MD simulation runs were performed for each molecule, i.e., with or without the inclusion of VS (MD or MD , respectively).…”

Imidazole in Aqueous Solution: Hydrogen Bond Interactions and Structural Reorganization with Concentration

“…A further improvement is achieved by adjusting the atomic charges through a fitting procedure using the molecular dipole and quadrupole moments as reference. 22 Moreover, as in pyridine, 21,49 the explicit description of the sp 2 LP of the nitrogen atom (through a centroid of a localized molecular orbital computed with the Pipek−Mezey procedure 5 ) allows to correctly describe the directional character of the hydrogen bond interactions, which are of fundamental importance for imidazole. The atomic charges of this force field, called improved, and obtained adopting the above discussed schemes (using Mulliken charges only as initial guess in the fitting procedure) are reported in Table 1 (the topological and parameter files are provided as the Supporting Information).…”

“…To this end, we followed a computational protocol to model the electrostatic potential of the imidazole ring similar to that adopted with success to simulate pyridine 21 and pyrrole. 22 In order to assess the structural properties of the hydrogen bond pattern in solvated imidazole, the imidazole-water Radial Distribution Function (RDF) from MD simulations, were compared to ab initio molecular dynamics simulations using the Car-Parrinello method (CPMD). [23][24][25] The presented ab initio results on solvated imidazole are not only important as a valuable reference for assessing the reliability of fixed charges force fields, but they are interesting per se, since CPMD is known to be particularly effective for the description of hydrogen bonded systems, realistically encompassing charge transfer and polarisation effects.…”

“…In the present study, given the deficiencies of the current AMBER, CHARMM, and OPLS force field implementations evidenced in the previously referenced studies, ,, we have developed a new force field for the imidazole molecule based on the fixed charges paradigm augmented by the introduction of an extra site (EP) accounting for the lone pair (LP) on the deprotonated nitrogen atom on the ring. To this end, we followed a computational protocol to model the electrostatic potential of the imidazole ring similar to that adopted with success to simulate pyridine and pyrrole …”

Tailor‐made computational protocols for precise characterization of small biological building blocks using QM and MM approaches

“…This is often necessary when dealing with the prediction of spectroscopic properties or extending FFs to excited electronic states. One simple alternative route, to fine‐tune accuracy versus transferability, could be to reparameterize only few terms of an existing literature FF to fit data obtained from high level of QM theory . This can be useful when handling large molecules (for instance, biopolymers) where most of the existing parameters are fully validated, but some novel functional groups are introduced, for example, to model the effect of an artificial modification .…”