Alexander E. Klimovitskii

Study of “Racemic Compound-Like” Behavior of Diastereomeric Mixture of Pinanyl Sulfoxides by X-Ray Diffraction, IR Spectroscopy, and DFT Calculations

Abstract The oxidation of a β-hydroxysulfide in the pinane series by use of m-chloroperbenzoic acid resulted in the formation of the corresponding β-hydroxysulfoxide as a mixture of two diastereomers in 4:5 ratio. According to single-crystal X-ray diffraction (XRD) results, it is established that the diastereomeric mixture of sulfoxides crystallizes in the “racemic compound-like” manner under formation of asymmetric dimers through S=O··H–O interactions. This asymmetric dimer formed from diastereomeric molecules is a structural unit in both crystal modifications, the triclinic and the monoclinic one. The behavior of the diastereomeric mixture of pinane derived sulfoxides in crystals, melts and in tetrachloromethane solutions was studied by IR spectroscopy. The density functional theory (DFT) method with 6-31G (d, p) basis set was used to calculate the optimized geometrical parameters and vibrational frequencies of different associates in solutions. The calculated vibrational frequencies are compared with experimental IR spectra. GRAPHICAL ABSTRACT

Additive cooperativity of hydrogen bonds in complexes of catechol with proton acceptors in the gas phase: FTIR spectroscopy and quantum chemical calculations

Experimental study of hydrogen bond cooperativity in hetero-complexes in the gas phase was carried out by IR-spectroscopy method. Stretching vibration frequencies of O-H groups in phenol and catechol molecules as well as of their complexes with nitriles and ethers were determined in the gas phase using a specially designed cell. O-H groups experimental frequency shifts in the complexes of catechol induced by the formation of intermolecular hydrogen bonds are significantly higher than in the complexes of phenol due to the hydrogen bond cooperativity. It was shown that the cooperativity factors of hydrogen bonds in the complexes of catechol with nitriles and ethers in the gas phase are approximately the same. Quantum chemical calculations of the studied systems have been performed using density functional theory (DFT) methods. It was shown, that theoretically obtained cooperativity factors of hydrogen bonds in the complexes of catechol with proton acceptors are in good agreement with experimental values. Cooperative effects lead to a strengthening of intermolecular hydrogen bonds in the complexes of catechol on about 30%, despite the significant difference in the proton acceptor ability of the bases. The analysis within quantum theory of atoms in molecules was carried out for the explanation of this fact.

The vibrational spectra and conformations of ethylbenzene

Infrared spectra (4000-250 cm-1) of the liquid, amorphous, crystalline solids and solutions in liquid krypton and Raman spectra (2500-20 cm-1) of the liquid as well as the amorphous and crystalline solids of ethylbenzene and its deuterated analogue-ethylbenzene-d(10) have been recorded. The spectra indicate that in the liquid and amorphous solids a small amount of a second conformer is present, whereas only one conformer remains in the crystalline phases. Assignments of the observed band wave numbers are discussed by comparison with normal mode wave numbers and IR and RS intensities calculated from ab initio 6-31G force fields and optimised geometries for both conformers for two species. All of the normal modes of conformers have been assigned.

Thermally induced diphenylalanine cyclization in solid phase

The reaction of cyclization of diphenylalanine in solid phase under heating was studied, which is a stage in formation of various nanostructures from this dipeptide. The temperature ranges of the reaction as well as of dehydration of clathrate of diphenylalanine with water were determined. Kinetic parameters of cyclization were estimated within the approaches of the non-isothermal kinetics (“model-free” kinetics and linear regression methods for detection of topochemical equation). The product of diphenylalanine cyclization was characterized by X-ray powder diffractometry, FTIR spectroscopy and TG/DSC analysis. Crystallization of diphenylalanine and cyclo(diphenylalanine) from methanol solutions was studied using atomic force microscopy. The results obtained may be useful for the design of new nanomaterials based on diphenylalanine at high temperatures.

When two symmetrically independent molecules must be different: “Crystallization-induced diastereomerization” of chiral pinanyl sulfone

According to X-ray data, homochiral pinanyl sulfone crystallizes as an asymmetric dimer formed by pairwise H-bonds involving stereochemically different oxygen atoms of sulfonyl groups of molecules A and B. Thus, a pro-R atom is invoked for the construction of a relevant H-bond in molecule A, but in the case of molecule B only a pro-S atom is involved. Newly formed chiral sulfur atoms take opposite chirality in molecules A and B, while the configuration of the pinane skeleton remains unchanged. Such a stereochemical transformation is called “crystallization-induced diastereomerization”. The stability of the asymmetric dimer found in the crystal was evaluated within the framework of DFT (B3LYP, 6-31G (d,p)) and studied via IR spectroscopy in solution.

Preparation and properties of two polymorphic modifications of β-hydroxysulfoxide of the pinane series

The oxidation was performed of 2-(6,6-dimethylbicyclo[3.1.1]hept-2-ylmethylsulfanyl)ethanol II synthesized by adding 2-mercaptoethanol to (−)-β-pinene in the presence of a Lewis acid. The sulfoxide obtained is present in two polymorphic structures with different physical properties, spectral characteristics, and fungicidal activity.

Extraordinary behavior of β-hydroxy sulfoxides and sulfone of pinane series

GRAPHICAL ABSTRACT ABSTRACT The “racemic compound-like” behavior, low-temperature conformational rearrangement and “crystallization-induced diastereomerization” of β-hydroxysulfoxides and sulfone of pinane series have been studied. It was established, that the sample of sulfoxide crystallizes as an asymmetric dimer containing a supramolecularcentro-symmetric moiety formed through S=O···H‒O interactions between two independent molecules. Moreover, it was found that this dimer can crystallize in two so-called “packing polymorphs”—monoclinic and triclinic ones. By transition from the room temperature to 150 К for both polymorphic forms conformational restructuring of a stable hydrogen-bonded synthon from “unfolded” form to “folded” one has been observed. The sample of sulfoxide is interesting as the first example of the co-crystallization of chiral sulfur compounds. Surprisingly we have found a similar H-bonded dimer, formed by independent molecules, where all sulfone molecules are identical in stereochemical aspect. We suggested to use the new term “crystallization-induced diastereomerization” for the description of the stereochemical process leading to the formation of sulfone dimer. From a supramolecular chemistry point of view, we can speak of the finding of a new robust and reproducible synthon. From a stereochemical point of view, an “enantiophilic” fragment was discovered—a β-hydroxysulfoxide or sulfone group, capable of recognizing its mirror image.

Thermodynamics of dissolution and infrared-spectroscopy of solid dispersions of phenacetin.

In this work enthalpies of dissolution in water of polyethylene glycols (PEGs) having an average molecular weight of 1000 and 1400, Pluronic-F127, phenacetin as well as the composites prepared from them were measured using solution calorimetry at 298.15 K. Intermolecular interaction energies of polymer-phenacetin were calculated on the basis of an additive scheme. It was shown that for mixtures with high content of polymer (>90 wt%) Pluronic-F127 has the highest solubilizing effect, while for mixtures with (4–6):1 polymer: phenacetin ratio the best solubilizing agent is PEG-1400. Infrared-spectra showed a decrease of the number of self-associated molecules of phenacetin with increasing of polymer content in the composites. The obtained results enabled us to identify the features of intermolecular interactions of polymers with a model hydrophobic drug and may be used for optimizing the conditions for preparing solid dispersions based on hydrophilic polymers.