Unveiling the structural organisation of carvacrol through X-ray scattering and molecular Dynamics: A comparative study with liquid thymol

Abstract

An integrated approach involving Small and Wide Angle X-ray scattering and computational tools, Molecular Dynamics (MD) and Density Functional Theory (DFT) calculations, was employed to describe the microscopic structural arrangement in carvacrol (2-methyl-5-(1-methylethyl)phenol) at 300 K and 353 K. Carvacrol is a phenol derivative, with an aromatic nature and amphiphilic features and is liquid at room temperature. Its structural organization in the liquid state was compared with the one found for its structural isomer, thymol (5-methyl-2-(1-methylethyl)phenol), at 353 K (in its liquid state), through MD simulations: significant differences between the two compounds have emerged. For carvacrol, at both 300 K and 353 K, there is an inclination for the aromatic rings to orient perpendicularly, maintaining a first neighbour separation of around 6 Å. Conversely, liquid thymol at 353 K exhibits a more heterogeneous structural organisation and is characterised by both parallel and antiparallel orientations of neighbour rings already at shorter distances of approximately 4.5 Å. On a local scale, liquid thymol tends to establish hydrogen bonds (HBs) between its hydroxyl groups, reminiscent of its solid crystalline form. Conversely, carvacrol exhibits a stronger inclination towards O-H···π hydrogen bonding interactions. On a mesoscopic scale, both carvacrol and thymol are characterised by an X-ray scattering low Q peak, which fingerprints the existence of nm-scale structural heterogeneities due to the segregation of HB-interacting polar moieties, embedded within the apolar matrix. Notably, the low Q peak is more pronounced in liquid thymol where the preferential HBs between hydroxyl groups have been observed. Overall, the different structural arrangements of liquid carvacrol and thymol have the potential to influence various bulk and macroscopic properties, including melting points and solvation capabilities. Given these differences, one might envisage the use of carvacrol as a replacement to thymol, in order to fine-tune specific chemical physical properties of applicative interest, including deep eutectic solvents formulation.