Ihsan A. Shehadi

Physicochemical properties of antifungal drug–cyclodextrin complexes prepared by supercritical carbon dioxide and by conventional techniques

Antifungal drugs are the most common systemic drugs used for the treatment of oropharyngeal candidiasis, which is the first symptom of HIV infection. However, the efficacy and bioavailability of these drugs have been limited by their poor aqueous solubility and dissolution rate. Therefore, the aim of this study was to investigate the effect of different preparation methods (i.e. kneading, coevaporation, sealed-heating, and a solid inclusion technique using supercritical carbon dioxide carrier (SC CO(2)-inclusion)) for obtaining solid inclusion complexes between beta-cyclodextrin and three antifungal drugs (itraconazole, econazole, and fluconazole). The physicochemical properties of the different products were characterized by differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR) and powder X-ray diffractometry (PXRD). For the complexes prepared by the SC CO(2)-inclusion method, the effects of temperature and pressure have also been investigated. Results suggested the possibility of complex formation between beta-cyclodextrin and the three antifungal agents, and indicated that inclusion formation was influenced by the preparation technique. SC CO(2)-inclusion method proved to be an effective technique for preparing solid-state inclusion complexes between beta-cyclodextrin and antifungal drugs, avoiding the use of organic solvents. Moreover, temperature of the SC CO(2) played a major role in promoting drug-carrier interactions, whereas pressure had limited effects.

Future directions in protein function prediction

New directions in computational methods for the prediction of protein function are discussed. THEMATICS, a method for the location and characterization of the active sites of enzymes, is featured. THEMATICS, for Theoretical Microscopic Titration Curves, is based on well-established finite-difference Poisson-Boltzmann methods for computing the electric field function of a protein. THEMATICS requires only the structure of the subject protein and thus may be applied to proteins that bear no similarity in structure or sequence to any previously characterized protein. The unique features of catalytic sites in proteins are discussed. Discussion of the chemical basis for the predictive powers of THEMATICS is featured in this paper. Some results are given for three illustrative examples: HIV-1 protease, human apurinic/apyrimidinic endonuclease, and human adenosine kinase.

Active site prediction for comparative model structures with thematics.

THEMATICS (Theoretical Microscopic Titration Curves) is a simple, reliable computational predictor of the active sites of enzymes from structure. Our method, based on well-established Finite Difference Poisson-Boltzmann techniques, identifies the ionisable residues with anomalous predicted titration behavior. A cluster of two or more such perturbed residues is a very reliable predictor of the active site. The protein does not have to bear any resemblance in sequence or structure to any previously characterized protein, but the method does require the three-dimensional structure. We now present evidence that THEMATICS can also locate the active site in structures built by comparative modeling from similar structures. Results are given for a total of 21 sets of proteins, including 21 templates and 83 comparative model structures. Detailed results are presented for three sets of orthologous proteins (Triosephosphate isomerase, 6-Hydroxymethyl-7,8-dihydropterin pyrophosphokinase, and Aspartate aminotransferase) and for one set of human homologues of Aldose reductase with different functions. THEMATICS correctly locates the active site in the model structures. This suggests that the method can be applicable to a much larger set of proteins for which an experimentally determined structure is unavailable. With a few exceptions, the predicted active sites in the comparative model structures are similar to that of the corresponding template structure.

A Hubbard model for the second hyperpolarizability in alternating polymers

Abstract The static second hyperpolarizability in low polymers of the type …ABAB… is studied using a two-band Hubbard Hamiltonian. For fully reduced bridged metallic polymers, there exists a non-zero value for the metal–ligand energy gap which corresponds to a γ of maximum magnitude. For mixed-valence bridged polymers, | γ | may be increased if the metal–ligand energy gap is increased. This means that | γ | may be enhanced significantly by synthetic alteration of the bridging ligand. Large, negative values for γ are predicted for polymers of the von Kameke type for the system in the mixed-valence state where the number of πd electrons equals twice the number of metal atoms minus one.

Introducing a Practice-Oriented Approach in the Physical Chemistry Instructional Laboratory

There remains a tendency to follow the traditional philosophy that physical principles are to be illustrated experimentally rather than applied in problem solving, often with complex apparatus that distracts students from the point of the experiment.