Showing papers by "Andrei V. Churakov published in 2020"

Cocrystals of Fluconazole with Aromatic Carboxylic Acids: Competition between Anhydrous and Hydrated Solid Forms

Abstract: Through cocrystallization of the broad-spectrum antifungal agent fluconazole (FLZ) with a number of nutraceuticals, we have isolated three distinct solid forms of the drug, namely, anhydrous cocrys...

Combined X-ray Crystallographic, IR/Raman Spectroscopic, and Periodic DFT Investigations of New Multicomponent Crystalline Forms of Anthelmintic Drugs: A Case Study of Carbendazim Maleate.

Abstract: Synthesis of multicomponent solid forms is an important method of modifying and fine-tuning the most critical physicochemical properties of drug compounds. The design of new multicomponent pharmaceutical materials requires reliable information about the supramolecular arrangement of molecules and detailed description of the intermolecular interactions in the crystal structure. It implies the use of a combination of different experimental and theoretical investigation methods. Organic salts present new challenges for those who develop theoretical approaches describing the structure, spectral properties, and lattice energy Elatt. These crystals consist of closed-shell organic ions interacting through relatively strong hydrogen bonds, which leads to Elatt > 200 kJ/mol. Some technical problems that a user of periodic (solid-state) density functional theory (DFT) programs encounters when calculating the properties of these crystals still remain unsolved, for example, the influence of cell parameter optimization on the Elatt value, wave numbers, relative intensity of Raman-active vibrations in the low-frequency region, etc. In this work, various properties of a new two-component carbendazim maleate crystal were experimentally investigated, and the applicability of different DFT functionals and empirical Grimme corrections to the description of the obtained structural and spectroscopic properties was tested. Based on this, practical recommendations were developed for further theoretical studies of multicomponent organic pharmaceutical crystals.

Crystalline Peroxosolvates: Nature of the Coformer, Hydrogen-Bonded Networks and Clusters, Intermolecular Interactions.

Abstract: Despite the technological importance of urea perhydrate (percarbamide) and sodium percarbonate, and the growing technological attention to solid forms of peroxide, fewer than 45 peroxosolvates were known by 2000. However, recent advances in X-ray diffractometers more than tripled the number of structurally characterized peroxosolvates over the last 20 years, and even more so, allowed energetic interpretation and gleaning deeper insight into peroxosolvate stability. To date, 134 crystalline peroxosolvates have been structurally resolved providing sufficient insight to justify a first review article on the subject. In the first chapter of the review, a comprehensive analysis of the structural databases is carried out revealing the nature of the co-former in crystalline peroxosolvates. In the majority of cases, the coformers can be classified into three groups: (1) salts of inorganic and carboxylic acids; (2) amino acids, peptides, and related zwitterions; and (3) molecular compounds with a lone electron pair on nitrogen and/or oxygen atoms. The second chapter of the review is devoted to H-bonding in peroxosolvates. The database search and energy statistics revealed the importance of intermolecular hydrogen bonds (H-bonds) which play a structure-directing role in the considered crystals. H2O2 always forms two H-bonds as a proton donor, the energy of which is higher than the energy of analogous H-bonds existing in isostructural crystalline hydrates. This phenomenon is due to the higher acidity of H2O2 compared to water and the conformational mobility of H2O2. The dihedral angle H-O-O-H varies from 20 to 180° in crystalline peroxosolvates. As a result, infinite H-bonded 1D chain clusters are formed, consisting of H2O2 molecules, H2O2 and water molecules, and H2O2 and halogen anions. H2O2 can form up to four H-bonds as a proton acceptor. The third chapter of the review is devoted to energetic computations and in particular density functional theory with periodic boundary conditions. The approaches are considered in detail, allowing one to obtain the H-bond energies in crystals. DFT computations provide deeper insight into the stability of peroxosolvates and explain why percarbamide and sodium percarbonate are stable to H2O2/H2O isomorphic transformations. The review ends with a description of the main modern trends in the synthesis of crystalline peroxosolvates, in particular, the production of peroxosolvates of high-energy compounds and mixed pharmaceutical forms with antiseptic and analgesic effects.

Effects of Concentration on Aggregation of BODIPY-Based Fluorescent Dyes Solution

Abstract: Despite significant progress in understanding of dye aggregation, there are still processes that need to be further explored and which can significantly affect aggregation. In this work it was shown that the aggregation of dyes is influenced not only by dye concentration, but also by solvent polarity. It was found that nature, positions and number of fluorescent peaks may be controlled by simultaneous varying of both water fraction and dye concentration. This effect is most pronounced for molecular rotors, which aggregates' geometry may be stabilized in different separate states depending on the aggregation degree. The concentration effect plays a significant role in dye aggregation and should be considered in new studies in order to prevent misinterpretation or to obtain new results in fields of molecular sensing or fine-tuning of fluorescence color. In this paper aggregation caused spectral changes are discussed in line with the dye structure preorganization as the strategy for the fine tuning of practically valuable spectral characteristics.

Stabilization of hydrogen peroxide by hydrogen bonding in the crystal structure of 2-aminobenzimidazole perhydrate

Abstract: 2-Aminobenzimidazole hemiperoxosolvate 2(C7H7N3)·H2O2 was synthesized and studied by single crystal X-ray analysis and periodic (solid-state) DFT calculations. The obtained compound, after urea and melamine peroxosolvates, is the third example of an H2O2 crystalline adduct stabilized with the maximum possible number of hydrogen bonds formed by one hydrogen peroxide molecule – 2 H-bonds as proton donors and 4 as acceptors. Due to the small size of the hydrogen peroxide molecule, its hydrogen bonding energy contributes the maximal impact and determines the relative value of the hydrogen bonding energy of the peroxosolvate crystal and can be suggested as an energetic criterion of perhydrate stability. The total energy of the 6 hydrogen bonds formed by one hydrogen peroxide molecule in all three compounds (∼140–∼170 kJ mol−1) was calculated and compared to the corresponding values for crystalline hydrogen peroxide and L-serine peroxosolvate. The total energy of the 4 hydrogen bonds of hydrogen peroxide molecule in crystalline H2O2 and L-serine peroxosolvate (150 and 113 kJ mol−1, respectively) was evaluated by solid-state DFT calculations.

Ciprofloxacin salts with benzoic acid derivatives: structural aspects, solid-state properties and solubility performance

Abstract: In this work, three new pharmaceutical hydrated salts of ciprofloxacin with selected derivatives of benzoic acid, namely 4-hydroxybenzoic acid, 4-aminobenzoic acid and gallic acid, were obtained and systematically investigated by several solid-state analytical techniques. In situ Raman spectroscopy was applied to elucidate the alternative pathways of the solid forms' formation under mechanochemical conditions. Crystal structure analysis and a CSD survey allowed us to establish a distinct supramolecular motif formed by infinite columnar stacks of ciprofloxacin dimers arranged in the “head-to-tail” manner. An alternative “head-to-head” packing arrangement was only observed in the crystal of the hydrated ciprofloxacin salt with 4-aminobenzoic acid. In addition, the pH-solubility behavior of the solid forms was thoroughly investigated. Furthermore, a distinct structure–property relationship between the specific features of the supramolecular organization of the hydrated salts and their solubility was observed and discussed.

Identification of a previously unreported co-crystal form of acetazolamide: a combination of multiple experimental and virtual screening methods.

Abstract: In the search for new co-crystal forms, many studies only consider one method of co-crystallisation which may lead to incorrect results. In this work, we demonstrate the efficiency of applying multiple experimental and virtual screening methods for a more comprehensive search for co-crystals of acetazolamide. A new co-crystal of acetazolamide with 4-aminobenzoic acid ([ACZ + PABA] (1 : 1)) was discovered, although previously, it had been found in the blind spot of the liquid-assisted grinding (LAG) screening method. The new co-crystal was investigated by different analytical techniques, including the powder and single crystal X-ray diffraction, differential scanning calorimetry, dissolution and solubility methods. The specific features of the mechanochemical formation process for [ACZ + PABA] (1 : 1) were studied. It was found that the appearance of the blind spot of the LAG screening method can be caused by a number of reasons; among those are the high sensitivity to the solvent choice and the low rate of the reagent conversion into the reaction product. A comparison of the ACZ co-crystals with 4-aminobenzoic and 4-hydroxybenzoic acids revealed their close resemblance in terms of the packing energy gain and the driving force of co-crystallization. Therefore, the experimental problems in the formation of the [ACZ + PABA] (1 : 1) co-crystal were associated with a number of kinetic reasons, e.g. the high energy barrier of the nucleation process and the low growth rate of the co-crystal. Using the co-crystal screening of acetazolamide as an example, the effectiveness of five different virtual methods for predicting co-crystal formation was assessed. In order to carry out the virtual screening based on the formation thermodynamics of a hypothetical co-crystal, for the first time ever we studied the ACZ sublimation process. Four out of the five virtual screening methods confirm the formation of the new [ACZ + PABA] (1 : 1) co-crystal.

Identification of Barium Hydroxo-Hydroperoxostannate Precursor for Low-Temperature Formation of Perovskite Barium Stannate.

Abstract: A breakthrough “superoxide colloidal solution route” for low-temperature synthesis of barium and strontium stannate perovskites and their doped analogues was recently introduced. The synthesis star...

dl-Piperidinium-2-carboxyl-ate bis-(hydrogen peroxide): unusual hydrogen-bonded peroxide chains.

Abstract: The title compound, C6H11NO2·2H2O2, is the richest (by molar ratio) in hydrogen peroxide among the peroxosolvates of aliphatic α-amino acids. The asymmetric unit contains a zwitterionic pipecolinic acid mol­ecule and two hydrogen peroxide mol­ecules. The two crystallographically independent hydrogen peroxide mol­ecules form a different number of hydrogen bonds: one forms two as donor and two as acceptor ([2,2] mode) and the other forms two as donor and one as acceptor ([2,1] mode). The latter hydrogen peroxide mol­ecule forms infinite hydrogen-bonded hydro­peroxo chains running along the c-axis direction, which is unusual for aliphatic α-amino acid peroxosolvates.

Hydroperoxo double hydrogen bonding: stabilization of hydroperoxo complexes exemplified by triphenylsilicon and triphenylgermanium hydroperoxides

Abstract: Triphenyl silicon hydroperoxide and its isostructural germanium complex were characterized by single crystal X-ray analysis revealing H-bonding of two triphenylhydroperoxocomplexes, with each hydroperoxo ligand acting as a hydrogen donor and a hydrogen acceptor. Only two other structures with localized protons of hydroperoxo complexes' main group elements (boron and tin) are known (compared to 130 p-block element peroxo compounds) and both exhibit the same hydroperoxo double hydrogen bonding motif. The reaction of the hydroperoxo complexes with triphenylgermanium chloride to give the dinuclear peroxobridged germanium complex demonstrates the higher reactivity of the hydroperoxo moieties compared to the peroxo moiety. DFT calculations provide an estimate of the hydroperoxo double hydrogen bond energies: 62.8 and 63.6 kJ mol−1 for triphenyl silicon, 63.6 and 65 kJ mol−1 for the germanium complex.

X-ray structure and DSC of mesomorphous 4-n-butyloxyphenyl-4’-methacryloyloxybenzoate, CH2=C(CH3)-COO-C6H4-COO-C6H4-O-C4H9

Abstract: The crystal structure of the title compound has been determined. The molecule is non-planar, the dihedral angle between the phenyl rings is equal to 84.2(10)°. In crystal, weak C-H…O hydrogen bonds...

Chromium complexes bearing disubstituted organophosphate ligands and their use in ethylene polymerization.

Abstract: The crystal structures of three unusual chromium organophosphate com­plexes have been determined, namely, bis­(μ-butyl 2,6-di-tert-butyl-4-methyl­phenyl hydro­gen phosphato-κO:κO′)di-μ-hydroxido-bis­[(butyl 2,6-di-tert-butyl-4-methyl­phenyl hydrogen phosphato-κO)(butyl 2,6-di-tert-butyl-4-methyl­phen­yl phosphato-κO)chromium](Cr—Cr) heptane disolvate or {Cr2(μ2-OH)2[μ2-PO2(OBu)(O-2,6-tBu2-4-MeC6H2)-κO:κO′]2[PO2(OBu)(O-2,6-tBu2-4-MeC6H2)-κO]2[HOPO(OBu)(O-2,6-tBu2-4-MeC6H2)-κO]2}·2C7H16, [Cr2(C19H32O4P)4(C19H33O4P)2(OH)2]·2C7H16, denoted (1)·2(hepta­ne), [μ-bis­(2,6-diiso­propyl­phen­yl) phos­phato-1κO:2κO′]bis­[bis­(2,6-diiso­propyl­phen­yl) phosphato]-1κO,2κO-chlorido-2κCl-tri­ethanol-1κ2O,2κO-di-μ-ethano­lato-1κ2O:2κ2O-dichromium(Cr—Cr) ethanol monosolvate or {Cr2(μ2-OEt)2[μ2-PO2(O-2,6-iPr2-C6H3)2-κO:κO′][PO2(O-2,6-iPr2-C6H3)2-κO]2Cl(EtOH)3}·EtOH, [Cr2(C2H5O)2(C24H34O4P)3Cl(C2H6O)3]·C2H6O, denoted (2)·EtOH, and di-μ-ethano­lato-1κ2O:2κ2O-bis­{­[bis­(2,6-diiso­propyl­phen­yl) hydrogen phosphato-κO][­bis­(2,6-diiso­propyl­phen­yl) phosphato-κO]chlorido­(ethanol-κO)chromium}(Cr—Cr) benzene disolvate or {Cr2(μ2-OEt)2[PO2(O-2,6-iPr2-C6H3)2-κO]2[HOPO(O-2,6-iPr2-C6H3)2-κO]2Cl2(EtOH)2}·2C6H6, [Cr2(C2H5O)2(C24H34O4P)2(C24H35O4P)2Cl2(C2H6O)2]·2C6H6, denoted (3)·2C6H6. Complexes (1)–(3) have been synthesized by an exchange reaction between the in-situ-generated corresponding lithium or potassium disubstituted phosphates with CrCl3(H2O)6 in ethanol. The subsequent crystallization of (1) from heptane, (2) from ethanol and (3) from an ethanol/benzene mixture allowed us to obtain crystals of (1)·2(hepta­ne), (2)·EtOH and (3)·2C6H6, whose structures have the monoclinic P21, ortho­rhom­bic P212121 and triclinic P\overline 1 space groups, respectively. All three com­plexes have binuclear cores with a single Cr—Cr bond, i.e. Cr2O6P2 in (1), Cr2PO4 in (2) and Cr2O2 in (3), where the Cr atoms are in distorted octa­hedral environments, formally having 16 ē per Cr atom. The com­plexes have bridging ligands μ2-OH in (1) or μ2-OEt in (2) and (3). The organophosphate ligands demonstrate terminal κO coordination modes in (1)–(3) and bridging μ2-κO:κO′ coordination modes in (1) and (2). All the com­plexes exhibit hydrogen bonding: two intra­molecular Ophos⋯H—Ophos inter­actions in (1) and (3) form two {H[PO2(OR)2]2} associates; two intra­molecular Cl⋯H—OEt hydrogen bonds additionally stabilize the Cr2O2 core in (3); two intra­molecular Ophos⋯H—OEt inter­actions and two O⋯H—O inter­molecular hydrogen bonds with a noncoordinating ethanol mol­ecule are observed in (2)·EtOH. The presence of both basic ligands (OH− or OEt−) and acidic [H(phosphate)2]− associates at the same metal centres in (1) and (3) is rather unusual. Com­plexes may serve as precatalysts for ethyl­ene polymerization under mild conditions, providing polyethyl­ene with a small amount of short-chain branching. The formation of a small amount of α-olefins has been detected in this reaction.