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A spectroscopic and computational study of a series of 2,5-bis(2-thien-2-ylethenyl) thiophene-based oligomers with a para-R-arylethenyl substituent is reported. The primary aim of this investigation is to increase understanding of how charge moves through these molecules by comparing the neutral and oxidized structures for each molecule. To this end, the B3LYP/6-31G(d) computational method was used to calculate the geometry and vibrational spectra for all molecules considered and their oxidation products. For vibrational data, mean absolute deviations for frequencies between experimental and theoretical results ranging from 2 to 18 cm-1were obtained. Experimental Raman spectroscopy, in conjunction with calculated bond length analyses, was used to gain an insight into the position and delocalization of the charged defect on the oxidized oligomers. The relative frequencies of different ethylene stretching modes served as a particularly useful probe in this regard. It was found that the ethenyl spacers do not impede -electron delocalization and, therefore, give rise to a longer conjugation length relative to the corresponding terthiophenes. Furthermore, the para-R-arylethenyl substituent was found to orientate the charged defect toward a specific region of the 2,5-bis(2-thien-2-ylethenyl)thiophene conjugation path. [ABSTRACT FROM AUTHOR]

The structural and electronic properties of neutral and oxidized terthiophenes substituted with polyaromatic systems have been investigated using a combination of both Raman and electronic absorption spectroscopy in conjunction with density functional theory calculations. Naphthylethenyl terthiophene exhibits structural and electronic properties, in both the neutral and oxidized species, that are dominated by the terthiophene backbone, in a manner similar to that previously reported for phenylethenylterthiophene. Anthracenylethenyl terthiophene, on the other hand, displays properties that are dominated by the anthracene group. Unlike both phenylethenyl and naphthylethenyl terthiophene, which have electronic absorption spectra dominated by transitions between molecular orbitals that are delocalized throughout the molecules, the absorption spectrum of anthracenylethenyl terthiophene consists of a simple addition of the absorption bands of the separate terthiophene and anthracenylethene chromophores. This is the result of a spatial partitioning of its molecular orbitals that effectively electronically decouples the anthracene and terthiophene moieties. Upon oxidation, the naphthylethenylterthiophene -dimerizes to form sexithiophene charged species and spectral signatures of the sexithiophene backbone are evident in both the electronic absorption and resonance Raman spectra. In contrast, these signatures are absent in the corresponding spectra of the oxidized anthracenylethenylterthiophene, suggesting that the anthracene group is the primary site of the structural changes induced by oxidation. [ABSTRACT FROM AUTHOR]

A number of case studies that illustrate how quantum chemistry may be used in studying pharmaceutical systems are reviewed. A brief introduction to quantum methods is provided and the use of these methods in understanding the structure and properties of indometacin and carbamazepine is discussed. The use of calculated structures and molecular electrostatic potentials in developing quantitative structure–activity relationships is discussed along with the use of computation chemistry to predict spectroscopic properties. [ABSTRACT FROM AUTHOR]

Terahertz pulsed spectroscopy (TPS) and terahertz pulsed imaging (TPI) are two novel techniques for the physical characterization of pharmaceutical drug materials and final solid dosage forms, utilizing spectral information in the far infrared region of the electromagnetic spectrum. This review focuses on the development and performance of pharmaceutical applications of terahertz technology compared with other tools for physical characterization. TPS can be used to characterize crystalline properties of drugs and excipients. Different polymorphic forms of a drug can be readily distinguished and quantified. Recent developments towards a better understanding of the fundamental theory behind spectroscopy in the far infrared have been discussed. Applications for TPI include the measurement of coating thickness and uniformity in coated pharmaceutical tablets, structural imaging and 3D chemical imaging of solid dosage forms. [ABSTRACT FROM AUTHOR]

The influence of various excipients on the conversion of carbamazepine polymorphs to the dihydrate in aqueous suspension has been investigated. Ten excipients having functional groups which were potentially able to form hydrogen bonds with carbamazepine (group 1: methylcellulose, hypromellose (hydroxypropyl methylcellulose), hydroxypropylcellulose (HPC), 2-hydroxyethylcellulose (HEC), carmellose sodium (sodium carboxymethylcellulose), cellobiose; group 2: povidone (polyvinylpyrrolidone), povidone-vinyl acetate copolymer (povidone/VA) and N-methyl-2-pyrrolidone; group 3: macrogol (polyethylene glycol) and polyethylene oxide–polypropylene oxide copolymer (PEO/PPO)) were selected. Carbamazepine polymorphic forms III and I were dispersed separately into each aqueous excipient solution (0.1%, w/v) for 30 min at room temperature. The inhibition effect of each excipient was quantified using Raman spectroscopy combined with multivariate analyses. The solubility parameter of each excipient was calculated and used for categorizing excipients. Excipients in groups 1 and 2, which had both low solubility parameters (< 27.0 MPa1/2) and strong hydrogen bonding groups, inhibited the conversion completely. With increasing solubility parameter, the inhibition effect decreased for group 1 excipients, especially for carbamazepine form I, which had a higher specific surface area. Also, the excipients of group 3, lacking strong hydrogen bonding groups, showed poor inhibition although they had low solubility parameters (< 21.0 MPa1/2). This study indicated the importance of both hydrogen bonding interaction and a suitable hydrophobicity (expressed by the solubility parameter) in the inhibition of the conversion of carbamazepine to the dihydrate. [ABSTRACT FROM AUTHOR]

Raman spectroscopy is experiencing a surge in interest in solid-state pharmaceutical applications. It is rapid, non-destructive, no sample preparation is required and measurements can be made in aqueous environments. It can be used for not only qualitative, but also quantitative, analysis. In this paper, the use of Raman spectroscopy for quantitative analysis of pharmaceutical solids is reviewed. The technique has been used for chemical and physical form analysis. Physical form analysis has involved quantification of polymorphism, hydrates, the amorphous form and, recently, protein conformation. Initially, simple powder systems were quantified, although this has since extended to complex pharmaceutical formulations, including tablets, capsules, microspheres and suspensions. Formulations have also been analysed through packaging. The characteristics of the technique make it ideal for process monitoring and it has been used to quantify changes in-situ during processes such as wet granulation and batch crystallisation. The theoretical basis of quantitative Raman spectroscopy, common data analysis approaches, including multivariate analysis, and sources of error in quantitative analysis are also discussed. [ABSTRACT FROM AUTHOR]

Amorphous materials are prevalent in the pharmaceutical setting. Whether they are a help or hindrance, their physico-chemical characteristics must be investigated. However, the amorphous form remains a challenge to characterise with many of its properties poorly understood. In this study, γ-crystalline and amorphous indometacin are investigated using vibrational spectroscopy and quantum chemical calculations. The structure of the single indometacin molecule and the dimer in the γ-form were optimised using density functional theory calculations. The optimised structures were similar to the conformations in the crystal form, suggesting that conformation of the molecules in the crystal may be close to the average molecular structure in less-ordered states. Infrared and Raman spectra were calculated from the optimised structures. Many modes in the calculated spectra could be matched with the experimental spectra of the γ-crystalline and amorphous forms, and a description of the matched modes has been provided. By analysis of the theoretical vibrational modes it was confirmed that the amorphous form of indometacin produced by quench cooling the melt consists predominantly of dimers, similar in structure to in the γ-crystalline form. In addition, differences in intermolecular bonding between the two forms were identified. Quantum mechanical calculations allow improved understanding of amorphous materials and their vibrational spectra. [ABSTRACT FROM AUTHOR]

The lowest energy transition of Ru(CN)4(ppb)2-(ppb dipyrido2,3-a:3‘,2‘-cphenazine), a metal-to-ligand charge transfer, has been probed using resonance Raman spectroscopy with excitation wavelengths (488, 514, 530, and 568 nm) spanning the lowest energy absorption band centered at 522 nm. Wave packet modeling was used to simultaneously model this lowest energy absorption band and the cross sections of the resonance Raman bands at the series of excitation wavelengths across this absorption band. A fit to within ±20% was obtained for the Raman cross sections, close to the experimental uncertainty which is typically 10−20%. values of 0.1−0.4 were obtained for modes which were either localized on the ppb ligand (345−1599 cm-1) or the CN modes (2063 and 2097 cm-1). DFT calculations reveal that the resonance Raman bands observed are due to modes delocalized over the entire ppb ligand. [ABSTRACT FROM AUTHOR]

The steady-state and transient emission properties of unsubstituted terthiophene and a series of 3‘-[E-2-(4-R-phenyl)ethenyl]-2,2‘:5‘,2‘ ‘-terthiophenes (where R = H, MeO, NH2, CN, NMe2, NO2) have been examined. The R = NO2 compound is nonemissive at room temperature in all solvents but cyclohexane. All of the other compounds show measurable steady-state emission in a variety of solvents. The behavior of these spectra may be split into two groups. The first group, those substituted compounds with R = CN, NH2 and NMe2, show solvatochromic behavior, where their Lippert−Mataga plots suggest changes in dipole upon photoexcitation ranging from 12.5 to 16.0 D. For the second group, where R = H and MeO (and unsubstituted terthiophene as well), the Lippert−Mataga plots indicate dipole moment changes ranging from 0 to 7.9 D. The difference in behavior between the two groups of emissive compounds can be attributed to a charge-transfer character of the emitting state in the first group. This conclusion is supported by density functional theory calculations, which show that the frontier MOs in the group one compounds are spatially separated whereas those of group two have frontier MOs that are delocalized over both the styryl and terthiophene moieties. Picosecond time-resolved fluorescence spectroscopy reveals that unsubstituted terthiophene has the shortest emission lifetime of 140 ps in acetonitrile. For the styryl substituted terthiophenes, the lifetimes are much longer and range from 320 to 670 ps for R = CN and NMe2 respectively, a result that can be explained in terms of a smaller rate of intersystem crossing in these compounds. [ABSTRACT FROM AUTHOR]

IR spectroscopy in concert with DFT calculations and resonance Raman spectroelectrochemistry has been used to identify the molecular orbital nature of the singly occupied molecular orbital (SOMO) in reduced Re(CO)3Cl(L) and Re(CO)3(4-Mepy)(L)complexes, where L 1,10-phenanthroline and its 4,7-diphenyl- and 3,4,7,8-tetramethyl-substituted analogues. The SOMO of each reduced species considered was found to be of b1symmetry, rather than the close lying orbital of a2symmetry (within a C2vsymmetry description of the phenanthroline moiety). This was deduced in a number of ways. First, the average carbonyl band force constants (kavkavreduced complex − kavparent complex) range from −57 to −41 N m-1for the series of compounds studied. The value of kavrelates to the extent of orbital overlap between the ligand MO and the metal d MO. These values are consistent with population of a b1MO because the wave function amplitude at the chelating nitrogens for this MO is significantly greater than that for a2MO. Second, calculations on singly reduced Re(CO)3(4-Mepy)(phen)and Re(CO)3(4-Mepy)(tem)predict population of a b2SOMO. The spectra predicted for these species are in close agreement with the vibrational spectroscopic data; for the IR data the shifts in the CO bands are predicted to 6 cm-1and the mean absolute deviation between calculated and measured Raman bands was found to be 10 cm-1. [ABSTRACT FROM AUTHOR]