8352 | Phys. Chem. Chem. Phys., 2019, 21, 8352--8364 This journal is © the Owner Societies 2019 Cite this: Phys. Chem. Chem. Phys., 2019, 21, 8352 The role of dispersion and anharmonic corrections in conformational analysis of flexible molecules: the allyl group rotamerization of matrix isolated safrole† Hongli Zhang, a Justyna Krupa, * b Maria Wierzejewska b and Malgorzata Biczysko * a Conformational changes of the monomeric safrole (5-(2-propenyl)-1,3-benzodioxole) isolated in low temperature xenon matrices were induced thermally or using narrow-band UV radiation. The rotation of the allyl group taking place in the studied matrices was followed by FTIR spectroscopy. Safrole represents a challenging example of a flexible molecule highlighting the importance of dispersion interactions and anharmonic effects in the structural, spectroscopic and energetic analysis. Structures of the safrole conformers, their energetics and infrared spectra have been calculated using various computational methods ranging from density functional theory (DFT) to coupled cluster (CC). The best theoretical results were obtained by integrating CCSD(T) energies including complete basis set extrapolation and core-valence corrections with B2PLYP-D3 equilibrium structures and hybrid B2PLYP-D3/B3LYP-D3 anharmonic computations for IR spectra and thermodynamics. I. Introduction Conformational analysis represents a first step toward a detailed characterization and understanding of the structure–function relationships of molecular systems. 1–3 In this respect spectro- scopic experiments on isolated bio- and organic-molecules allow detection of different binding schemes and three-dimensional (3D) conformations without the perturbing effects of the environment. 4,5 These state-of-the-art studies are performed via microwave (MW) measurements, 6–10 or by an analysis of vibrational features in infrared (IR), Raman, resonance Raman, UV-vis or fluorescence spectra, 11–14 with the most effective routes represented by the integration of rotational and vibrational techniques. 15 Detection of multiple 3D-geometries concomitantly present in an experi- mental mixture can be facilitated by ‘‘in situ’’ structural changes induced either by thermal variations 16,17 or by the interaction with near-IR (NIR) to ultraviolet (UV) light. 17–24 These sophisticated experiments need to be supported by accurate and reliable computational studies allowing one to link the rich experimental data to the desired information on the structure and properties of complex molecular systems. 25 It has been shown that the inclusion of dispersion effects is often crucial for correct determination of the experimental three- dimensional structures. 12,26–28 Moreover, for flexible molecules, reliable prediction of free energies and molecular spectra of different conformers under specific experimental conditions often requires going beyond the simplest harmonic approximation. 29–31 The subject of this work is safrole (5-(2-propenyl)-1,3-benzodioxol (SF)), an abundant natural product usually extracted from sassafras oil or other essential oils. This compound is a derivative of eugenol, which is one of the most abundant species in the plant phenols family. 32–34 Both safrole and eugenol contain an allyl substituent group and in safrole the 1,3-dioxolane ring (methylenedioxy unit) is also present (see Chart 1). These functional groups lead to some conformational flexibility of SF, which in turn induces interesting chemical functionality and reactivity suggesting its use as a versatile drug component. Although regarded as a weak carcinogen, safrole was found to display antitumor activity when conjugated with amino acid residues or small peptides. 35 Safrole is also used to manufacture pesticides, fragrances, and other chemicals. Oguzie et al. 36 have found, using different experimental and theoretical techniques, the corrosion inhibiting effect of acid extracts of natural products (Piper guineense), containing safrole among other components, on mild steel. Safrole and isosafrole were proved to be useful methylenedioxy compounds to maximize the detection potential of extasy samples by the canines. 37 In the present paper we focus on conformational changes of safrole isolated in low temperature xenon matrices, which are a International Centre for Quantum and Molecular Structures, Department of Physics, College of Sciences, Shanghai University, 99 Shangda Road, Shanghai, 200444, China. E-mail: biczysko@shu.edu.cn b Faculty of Chemistry, University of Wroclaw, Joliot-Curie 14, 50-383 Wroclaw, Poland. E-mail: justyna.krupa@chem.uni.wroc.pl † Electronic supplementary information (ESI) available. See DOI: 10.1039/c9cp00926d Received 15th February 2019, Accepted 26th March 2019 DOI: 10.1039/c9cp00926d rsc.li/pccp PCCP PAPER Published on 27 March 2019. Downloaded by Uniwersytet Wroclawski on 9/10/2021 11:17:16 AM. View Article Online View Journal | View Issue