TY - JOUR

T1 - Seeking the best model for non-covalent interactions within the crystal structure of meloxicam

AU - Fedorov, Alexey Yu

AU - Drebushchak, Tatiana N.

AU - Tantardini, Christian

N1 - Publisher Copyright: © 2019 Elsevier B.V.

PY - 2019/6/1

Y1 - 2019/6/1

N2 - In crystals, molecules are linked by different types of non-covalent interactions (NCIs). Sometimes it can be an intricate task to define without resorting to calculations what type of NCIs is mainly responsible for maintaining the structure. One of such examples is meloxicam in the polymorphic form I, for which two controversial models describing NCIs are known to date. These models proposed by Cheney et al. (2010), and Tumanov et al. (2012), differ in structural motifs and a presence of particular types of interactions therein. However, they both rely on geometrical parameters only and were not confirmed quantitatively. Here we show the final model of NCIs within the crystal structure of meloxicam polymorph I supported by DFT calculations, Hirshfeld surface analysis and reduced density gradient (RDG) investigation. We found that both types of weak van der Waals interactions described in the previously proposed models (namely, S⋯O and O[sbnd]H⋯O contacts) are actually present in the structure and take part in linking the N[sbnd]H⋯O-bonded meloxicam dimers with each other. These dimers are formed by medium-strength H-bonds and represent the main building blocks of the structure. Our study demonstrates how a model of NCIs can be unambiguously revealed by means of different computational tools. We hope that the results obtained in the present work will be useful for further studies of meloxicam, its co-crystals and analogous compounds.

AB - In crystals, molecules are linked by different types of non-covalent interactions (NCIs). Sometimes it can be an intricate task to define without resorting to calculations what type of NCIs is mainly responsible for maintaining the structure. One of such examples is meloxicam in the polymorphic form I, for which two controversial models describing NCIs are known to date. These models proposed by Cheney et al. (2010), and Tumanov et al. (2012), differ in structural motifs and a presence of particular types of interactions therein. However, they both rely on geometrical parameters only and were not confirmed quantitatively. Here we show the final model of NCIs within the crystal structure of meloxicam polymorph I supported by DFT calculations, Hirshfeld surface analysis and reduced density gradient (RDG) investigation. We found that both types of weak van der Waals interactions described in the previously proposed models (namely, S⋯O and O[sbnd]H⋯O contacts) are actually present in the structure and take part in linking the N[sbnd]H⋯O-bonded meloxicam dimers with each other. These dimers are formed by medium-strength H-bonds and represent the main building blocks of the structure. Our study demonstrates how a model of NCIs can be unambiguously revealed by means of different computational tools. We hope that the results obtained in the present work will be useful for further studies of meloxicam, its co-crystals and analogous compounds.

KW - DFT calculations

KW - Hirshfeld surface

KW - Non-covalent interactions

KW - Reduced density gradient

KW - ACCURATE

KW - PHARMACOKINETICS

KW - CO-CRYSTALS

KW - BOND

KW - EXPLORING INTERMOLECULAR INTERACTIONS

KW - PROGRAM

UR - http://www.scopus.com/inward/record.url?scp=85064525678&partnerID=8YFLogxK

U2 - 10.1016/j.comptc.2019.04.012

DO - 10.1016/j.comptc.2019.04.012

M3 - Article

AN - SCOPUS:85064525678

VL - 1157

SP - 47

EP - 53

JO - Computational and Theoretical Chemistry

JF - Computational and Theoretical Chemistry

SN - 2210-271X

ER -