Andris Actins

Protonation effects on the UV/Vis absorption spectra of imatinib: A theoretical and experimental study

An experimental and theoretical investigation of protonation effects on the UV/Vis absorption spectra of imatinib showed systematic changes of absorption depending on the pH, and a new absorption band appeared below pH 2. These changes in the UV/Vis absorption spectra were interpreted using quantum chemical calculations. The geometry of various imatinib cations in the gas phase and in ethanol solution was optimized with the DFT/B3LYP method. The resultant geometries were compared to the experimentally determined crystal structures of imatinib salts. The semi-empirical ZINDO-CI method was employed to calculate the absorption lines and electronic transitions. Our study suggests that the formation of the extra near-UV absorption band resulted from an increase of imatinib trication concentration in the solution, while the rapid increase of the first absorption maximum could be attributed to both the formation of imatinib trication and tetracation.

The effect of pH on polymorph formation of the pharmaceutically active compound tianeptine

The anti-depressant pharmaceutical tianeptine has been investigated to determine the dynamics of polymorph formation under various pH conditions. By varying the pH two crystalline polymorphs were isolated. The molecular and crystal structures have been determined to identify the two polymorphs. One polymorph is an amino carboxylic acid and the other polymorph is a zwitterion. In the solid state the tianeptine moieties are bonded through hydrogen bonds. The zwitterion was found to be less stable and transformed to the acid form. During this investigation an amorphous form was identified.

Application of LA-ICP-MS as a rapid tool for analysis of elemental impurities in active pharmaceutical ingredients.

The control of inorganic contaminants in active pharmaceutical ingredients has a significant role in the quality control of drug products. The concentration limits for metal residues in drug products have been defined by various regulatory guidelines. Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) is a powerful and fast analytical technique for multi-elemental analysis. A disadvantage in using LA-ICP-MS method is the lack of matrix reference materials for validation and calibration purposes. This article focuses on the handling strategy of laboratory-made matrix calibration standards for the quantification of elemental impurities in an active pharmaceutical ingredient by LA-ICP-MS.

Modelling phase transition kinetics of chenodeoxycholic acid with the Runge-Kutta method.

The phase transition kinetics of two chenodeoxycholic acid polymorphic modifications-form I (stable at high temperature), form III (stable at low temperature) and the amorphous phase has been examined under various conditions of temperature and relative humidity. Form III conversion to form I was examined at high temperature conditions and was found to be non-spontaneous, requiring seed crystals for initiation. The formation kinetic model of form I was created incorporating the three-dimensional seed crystal growth, the phase transition rate proportion to the surface area of form I crystals, and the influence of the amorphous phase surface area changes with an empirical stage pointer q that contained the incomplete transition of the amorphous phase to form I with a residue omega(A)(infinity). The extent of transition and the phase transition rate constant depended on form I seed crystal amount in the raw mixture, and on the sample preparation. To describe phase transition kinetic curves, we employed the Runge-Kutta differential equation numeric solving method. By combining the Runge-Kutta method with the multi-point optimization method, the average quadratic deviation of the experimental results from one calculated series was under 2%.

Optical properties of thin metal films with nanohole arrays on porous alumina–aluminum structures

A multilayer system is formed by the deposition of a 10–35 nm thin Au or Ag film with 18–25 nm diameter holes on 75–280 nm thick layers of porous anodized aluminum oxide (AAO) supported by a bulk sheet of aluminum. We present a detailed study of system parameters, which influence the optical response, including the porosity, metal layer thickness and crystallographic orientation of the Al substrate. The spectral properties are mainly governed by the interference of the reflections from the Al substrate and the thin metal film separated by the AAO layer. An enhanced plasmonic attenuation component near 650 nm for the Au films with holes can be observed when the interferometric anti-reflection condition is fulfilled close to this particular wavelength.

Two polymorphs of afobazole from powder diffraction data.

Afobazole {systematic name: 2-[2-(morpholin-4-yl)ethylsulfanyl]-1H-benzimidazole} is a new anxiolytic drug and Actins, Auzins & Petkune [(2012). Eur. Patent EP10163962] described four polymorphic modifications. In the present study, the crystal structures of two monoclinic polymorphs, 5-ethoxy-2-[2-(morpholin-4-ium-4-yl)ethylsulfanyl]-1H-benzimidazol-3-ium dichloride, C15H23N3O2S(2+)·2Cl(-), (II) and (IV), have been established from laboratory powder diffraction data. The crystal packing and conformation of the dications in (II) and (IV) are different. In (II), there are channels in the [001] direction, which offer atmospheric water molecules an easy way of penetrating into the crystal structure, thus explaining the higher hygroscopicity of (II) compared with (IV).

Pimobendan B from powder diffraction data

The title molecule, C19H18N4O2 {systematic name: (RS)-6-[2-(4-methoxyphenyl)-1H-benzimidazol-5-yl]-5-methyl-4,5-dihydropyridazin-3(2H)-one}, adopts an extended conformation. The dihedral angles between the central benzimidazole ring sytem and the pendant methoxyphenyl and pyridazinone residues are 1.41 (18) and 9.7 (3)°, respectively. In the crystal, N—H⋯N hydrogen bonds link the imadazole groups into [001] chains, and pairs of N—H⋯O hydrogen bonds link the pyridazinone groups into dimers. Together, these generate a two-dimensional supramolecular structure parallel to (010). The layers are linked by C—H⋯π interactions.

7-[(3-Chloro-6-methyl-6,11-dihydro-dibenzo[c,f][1,2]thia-zepin-11-yl)amino]-hepta-noic acid S,S-dioxide hydro-chloride.

In the title compound, C21H26ClN2O4S.Cl, also known as tianeptine hydrochloride, the seven-membered ring adopts a boat conformation. The dihedral angle between the mean planes of the benzene rings is 44.44 (7)°. There is an intramolecular hydrogen bond formed via S= O⋯H—N. In the crystal, molecules are connected via pairs of N—H.·O, N—H⋯Cl and O—H⋯Cl hydrogen bonds, forming inversion dimers, which are consolidated by C—H⋯O interactions. The dimers are linked by C—H⋯O and C—H⋯Cl interactions, forming a two-dimensional network lying parallel to (011).

Dipotassium 4,4'-(hexane-3,4-di-yl)bis-(benzene-sulfonate) dihydrate.

The anion of the title compound, also called sygethin dihydrate, 2K+·C18H20O6S2 2−·2H2O, has crystallographic inversion symmetry. The K+ cation is surrounded by eight O atoms in a distorted cubic coordination geometry, forming extended K—O—S networks. There are also O—H⋯O hydrogen bonds.