Bolesław Barszcz

Solid-state stability study of meropenem – solutions based on spectrophotometric analysis

BackgroundB-Lactam antibiotics are still the most common group of chemotherapeutic drugs that are used in the treatment of bacterial infections. However, due to their chemical instability the potential to apply them as oral pharmacotherapeutics is often limited and so it is vital to employ suitable non-destructive analytical methods. Hence, in order to analyze such labile drugs as β-lactam analogs, the application of rapid and reliable analytical techniques which do not require transferring to solutions or using organic solvents, following the current green approach to pharmaceutical analysis, is necessary. The main objective of the present research was to develop analytical methods for the evaluation of changes in meropenem in the solid state during a stability study.ResultsThe UV, FT-IR and Raman spectra of meropenem were recorded during a solid-state stability study. The optimum molecular geometry, harmonic vibrational frequencies, infrared intensities and Raman scattering activities were calculated according to the density-functional theory (DFT/B3LYP method) with a 6-31G(d,p) basis set. As the differences between the observed and scaled wavenumber values were small, a detailed interpretation of the FT-IR and Raman spectra was possible for non-degraded and degraded samples of meropenem. The problem of the overlapping spectra of meropenem and ring-containing degradation products was solved by measuring changes in the values of the first-derivative amplitudes of the zero-order spectra of aqueous solutions of meropenem. Also, molecular electrostatic potential (MEP), front molecular orbitals (FMOs) and the gap potential between highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) were determined.ConclusionsBased on the findings of this work, it appears possible to use time-saving and reliable spectrophotometric analytical methods, supported by quantum-chemical calculations, for solid-state stability investigations of meropenem. The methods developed for this study may be considered a novel, green solution to pharmaceutical analysis of labile drugs – an alternative for the recommended chromatographic procedures.

New oxovanadium(IV) complexes with pincer ligand obtained in situ: experimental and theoretical studies on the structure, spectroscopic properties and antitumour activity

Experimental and theoretical studies on the structure and spectroscopic properties of two complexes: [VOL1(NCS)2] (1) and [VOL1(NCS)2]·C6H5CH3 (2) where L1-N,N-bis(3,5-dimethylpyrazol-1-ylmethyl)amine have been reported. The products, isolated in a one-pot synthesis, contain a multipodal pincer ligand L1 obtained in situ from the system containing 1-hydroxymethyl-3,5-dimethylpyrazole (L) as one of the substrates. The crystal structure, electronic (UV-VIS) and infrared (IR) spectra of the complexes have been analyzed. The combined use of experiments and computations allowed a firm assignment of the majority of the observed electronic and vibrational transitions. Theoretical (DFT) calculations have been carried out at the B3LYP/LanL2DZ level to investigate the geometry of 1 and 2. They were found to be in a good agreement with the experimental results. Additionally the biological activity of complex 2 was investigated. Complex 2 exhibited anti-proliferative activity towards a panel of human cancer cells (hepatocellular carcinoma Hep G2, lung carcinoma A549, colorectal adenocarcinomas SW 480 and SW 620). The anti-proliferative potency of complex 2 and its higher selectivity towards cancer cells than those of the vanadium salt tested, makes it an interesting candidate for further investigation of its anti-cancer properties.

The use of UV, FT-IR and Raman spectra for the identification of the newest penem analogs: Solutions based on mathematic procedure and the density functional theory

The application of ultraviolet, FT-IR and Raman spectra was proposed for identification studies of the newest penem analogs (doripenem, biapenem and faropenem). An identification of the newest penem analogs based on their separation from related substances was achieved after the application of first derivative of direct spectra in ultraviolet which permitted elimination of overlapping effects. A combination of experimental and theoretical studies was performed for analyzing the structure and vibrational spectra (FT-IR and Raman spectra) of doripenem, biapenem and faropenem. The calculations were conducted using the density functional theory with the B3LYP hybrid functional and 6-31G(d,p) basis set. The confirmation of the applicability of the DFT methodology for interpretation of vibrational IR and Raman spectra of the newest penem analogs contributed to determination of changes of vibrations in the area of the most labile bonds. By employing the theoretical approach it was possible to eliminate necessity of using reference standards which - considering the instability of penem analogs - require that correction coefficients are factored in.

Raman and infrared studies of molecular orientation in fullerene–thiophene films

The paper deals with spectral studies (IR absorption, IR reflection–absorption, Raman scattering, and electronic absorption) of Langmuir–Blodgett layers of selected fullerene–thiophene dyads; some information on preparation and properties of the layers are also given. The spectra were recorded with unpolarised and polarised light (p-polarisation and s-polarisation) to receive data on orientation of the dyads with respect to the solid substrate and on interaction of the dyads with gold substrates. The comparison of the dyad spectra suggests redistribution of charges in both moieties of the dyads after films deposition on the substrate. We have shown that the polarised reflection–absorption spectra of the thin films are strongly dependent on the light polarisation. From the analysis of the data on the basis of the results obtained from various spectral methods it was concluded that the Langmuir–Blodgett layers are ordered and some parts of the dyads are oriented.

Solid-state stability studies of faropenem based on chromatography, spectroscopy and theoretical analysis.

Abstract Aim: The purpose of this study was to investigate the stability of faropenem in solid state. Results: The kinetic and thermodynamic parameters of degradation of faropenem were studied using an RP-HPLC method while the changes of spectral properties were investigated using derivative UV and FT-IR. Quantum-chemical calculations, based on the density functional theory, were carried out to support the estimation of the intra-ring stresses of faropenem and for theoretical interpretation of the spectra. The degradation of faropenem was a first-order reaction depending on the substrate concentration at an increased relative humidity and in dry air. The dependence ln k = f(1/T) became the ln k = (2.03 ± 3.22) × 104–(9761 ± 3052)(1/T) in dry air and ln k = (1.25 ± 0.22) × 105–(9004 ± 3479)(1/T ) at 90.0% RH. The thermodynamic parameters Ea, ΔH≠a, and ΔS≠a of the degradation of faropenem were calculated. The dependence ln k = f(RH%) assumed the form ln k = (7.58 ± 1.88) × 10−2 (RH%) – (5.90 ± 3.90) × 10−8. Conclusions: Stability studies of faropenem showed that the fusion of β-lactam and thiazolidine rings reduces the intra-ring stress, leading to a lower susceptibility to degradation in dry air and at increased RH.

Spectroscopic properties and orientation of molecules in Langmuir-Blodgett layers of selected functionalized fullerenes.

Vibrational properties of two fullerene derivatives: C60TZ-OT-5 (1) and C60TH-3HX (2) have been studied using infrared absorption and Raman scattering spectroscopies. Additionally, quantum chemical calculations of the equilibrium geometry and normal mode vibrations of these functionalized fullerenes were performed. It was stated that despite of distinct structural differences between the investigated molecules, their experimental spectra are quite similar and correspond well with the calculated ones. The orientation of the molecules in the Langmuir-Blodgett films was evaluated.

Morphology and molecular arrangement of perylene-3,4,9,10-(n-pentylester) in thin layers obtained by zone-casting

Liquid-crystalline perylene-3,4,9,10-tetra-(n-pentylester) zone-casted on hydrophilic glass substrates forms characteristic belt-like structures which are observed under optical microscope and atomic force microscope. Polarised Raman scattering spectra reveal the presence of anisotropic alignment of the molecules inside the obtained structures. Moreover, the absorption and fluorescence spectra confirm molecular aggregation in the belt-like structures. The research shows, that the belt-like structures are created by columns of molecules with the edge-on alignment on the glass substrate. Such organisation of the molecules is confirmed by spectroscopic methods. These structures can be interesting from the point of view of organic electronics.

Vibrational spectra of two BEDT-TTF-based organic conductors: charge order

Infrared and Raman investigations of two phases of bis(ethylenedithio)tetrathiafulvalene (BEDT-TTF) based organic conductors with the same CF3CF2SO3− anion: β′-(BEDT-TTF)2CF3CF2SO3 and δ′-(BEDT-TTF)2CF3CF2SO3, are shortly reviewed and compared with the most typical infrared properties of the family of (BEDT-TTF)2RR′SO3 organic conductors, where R = SF5, CF3, and R′ are CH2, CF2, CHF, CHFCF2, and CH2CF2. The role of the molecular structur and spatial organization of the counterions is discussed.

Quantum Dot and Fullerene with Organic Chromophores as Electron-Donor-Acceptor Systems

This review paper is focused on the research of molecular mechanisms occurring in porphyrin-like systems such as porphyrins, phthalocyanines, and corroles as well as in chromophore-semiconductor quantum dot (QD-CdSe/ZnS) or corrole-fullerene (C60) as electron-donor-acceptor unites. The basic spectroscopic investigations describe properties of materials in organic solutions in the ultraviolet, visible, and infrared ranges and in a form of Langmuir and Langmuir–Blodgett molecular nanolayers to get knowledge on photophysics of dyes and the influence of QD and C60 on the electron redistribution within the molecular structures. The studies also allowed to explain the impact of solvent on the spectroscopic properties of corroles and on the redistribution of the π-electrons in the excited state. The fluorescence studies very evidently showed strong interaction between chromophores and C60 or QD and clearly demonstrated the strong donor-acceptor nature of the phthalocyanines-quantum dot and the corrole-fullerene dyad. In addition, spectroscopic studies in polarized light allowed determining molecular arrangement of the chromophore molecules in the Langmuir–Blodgett layers with respect to solid substrates. The computer calculations (TD-DFT theory) confirmed the experimental results, in particular the redistribution of the π-electrons in the excited state and the location of HOMO and LUMO levels. The DFT calculations let also to evaluate the reorganization energy values for the set of free-base corroles and C60 fullerene. In this review, it was shown the electron-donor-acceptor character of the systems composed of: porphyrin-quinone, phthalocyanines-QD, corroles-C60 dyads. It has been demonstrated potential capabilities of the photoactive organic materials with QD and fullerene in the future applications in many areas of optoelectronic and in the process of converting solar energy into electric energy in solar cells.

Stability of Epidoxorubicin Hydrochloride in Aqueous Solutions: Experimental and Theoretical Studies

The first-order degradation kinetics of epidoxorubicin were investigated as a function of pH, temperature, and buffers concentrations. The degradation was followed by HPLC. Buffer catalysis was observed in acetate and phosphate buffers. The pH-rate profiles were obtained at 333, 343, 353, and 363 K. The pH-rate expression was , where , , and are the second-order rate constants (mol−1 L s−1) for hydrogen ion activity and for hydroxyl ion activity, respectively, and and are the first-order constants (s−1) for spontaneous reaction under the influence of water. Epidoxorubicin demonstrates the greatest stability in the pH range 3–5. The electrostatic molecular potential orbitals HOMO-LUMO were also defined in order to determine the cause of the reactivity of particular epidoxorubicin molecule domains in solutions with various pH values.