Role of Human Liver Microsomes in In Vitro Metabolism of Drugs—A Review

Drug metabolism studies are essential and necessary during the evaluation of drugs. This review discusses the in vitro human liver models to estimate the drug metabolic fates in vivo. Different approaches are provided and emphasis is placed on the potential of human liver microsomes for drug metabolism and inhibition studies. The methodology for these studies using human liver microsomes, applications of human liver microsomes, and the drugs studied by human liver microsomes are listed. Human liver microsomes represent a critical experimental model for the evaluation of drug metabolites with a high probability of clinical success.     

Self-organization-induced three-dimensional honeycomb pattern in structure-controlled bulky methacrylate polymers: Synthesis, morphology, and mechanism of pore formation

Here we report, for the first time, a novel molecular design for three-dimensional honeycomb structures through a self-organization of hydrogen-bonded bulky anchoring group in a methacrylic polymer backbone. The polymerizable monomer design includes a methacrylic double bond linked to various hydrophobic anchoring units such as ethane, n-decane, tricyclodecane (TCD), and adamantane via a hydrogen-bonded cycloaliphatic urethane linkage. The structures of the polymers were confirmed by nuclear magnetic resonance (NMR) and the molecular weights of the polymer were determined by gel permeation chromatography (GPC). The methacrylate polymers having tricyclodecane and adamantane bulky anchoring groups self-organized to produce three-dimensional honeycomb patterns in tetrahydrofuran-water solvent mixture at ambient conditions, whereas its linear analogues (ethane, n-decane) failed to produce any micropattern. The scanning electron microscopy (SEM) analysis of the above-prepared polymer films revealed that the structure of the polymer played a major role in the formation of the honeycomb patterns. The solution Fourier transform infrared (FTIR) measurements confirmed that the bulky tricyclodecane and adamantane polymers have strong hydrogen-bonding interaction compared to that of their linear analogues, which is the driving force for the micropatterns. Transmission electron microscopy (TEM) and atomic force microscopy (AFM) analysis of the bulky polymers revealed that the polymers exist as vesicles or micelles in the solution, which leads to the formation of the honeycomb pattern. The honeycomb pattern formation in the bulky polymer systems suggests that two cooperative factors such as hydrogen-bonding interaction and hydrophobicity of bulky anchoring units are necessary to induce three-dimensional honeycomb structures. To investigate the effect of molecular weights and its distribution on the self-organization process, both benzoyl peroxide (BPO) initiated free radical and atom transfer radical polymerization (ATRP) techniques were employed for the polymerization. Micropores formed irrespective of differences in molecular weight and polydispersity index (PDI); however, the pore size distribution was influenced by both molecular weights and PDI. Low molecular weight samples afforded polydisperse pores with the ATRP samples with more narrow PDI producing pores with large dimensions. The approach has also been investigated for polystyrene-bulky methacrylic copolymer, and the results revealed that uniform honeycomb patterns were produced for copolymers having more than 50 mol % incorporation of bulky units.     

Prospects of conducting polymers in biosensors

Applications of conducting polymers to biosensors have recently aroused much interest. This is because these molecular electronic materials offer control of different parameters such as polymer layer thickness, electrical properties and bio-reagent loading, etc. Moreover, conducting polymer based biosensors are likely to cater to the pressing requirements such as biocompatibility, possibility of in vivo sensing, continuous monitoring of drugs or metabolites, multi-parametric assays, miniaturization and high information density. This paper deals with the emerging trends in conducting polymer based biosensors during the last about 5 years.     

Temperature and 8 MeV electron irradiation effects on GaAs solar cells

GaAs solar cells hold the record for the highest single band-gap cell efficiency. Successful application of these cells in advanced space-borne systems demand characterization of cell properties like dark current under different ambient conditions and the stability of the cells against particle irradiation in space. In this paper, the results of the studies carried out on the effect of 8 MeV electron irradiation on the electrical properties of GaAs solar cells are presented. The I–V (current-voltage) characteristics of the cells under dark and AM1.5 illumination condition are studied and 8 MeV electron irradiation was carried out on the cells where they were exposed to graded doses of electrons from 1 to 100 kGy. The devices were also characterized using capacitance measurements at various frequencies before and after irradiation. The effect of electron irradiation on the solar cell parameters was studied. It is found that only small changes were observed in the GaAs solar cell parameters up to an electron dose of 100 kGy, exhibiting good tolerance for electrons of 8 MeV energy.     

Hydrogen bonding and rate enhancement in the photoinduced polymerization of telechelic urethane methacrylates based on a cycloaliphatic system: Tricyclodecane dimethanol

A new class of telechelic urethane methacrylic crosslinkers, based on a cycloaliphatic system (tricyclodecane dimethanol and tricyclodecane monomethanol), was synthesized. The synthesis was achieved by a two‐step condensation of 1,6‐hexamethylene diisocyanate or isophorone diisocyanate with tricyclodecane dimethanol and capping with hydroxyethyl methacrylate. Samples of hexanediol diacrylate, tricyclodecane monomethacrylate, and tricyclodecane dimethacrylate were used as non‐hydrogen‐bonding monomers for comparative studies of the curing kinetics. The photopolymerization of these telechelic systems was investigated with UV irradiation in the presence of 2,2‐diethoxy acetophenone as the photoinitiator, and the kinetics were followed by the monitoring of the double‐bond conversion at 815 cm^?1 with Fourier transform infrared spectroscopy. The hydrogen‐bonded crosslinkers had higher double‐bond conversions than their non‐hydrogen‐bonded counterparts under identical conditions. The higher cure rate could be explained by hydrogen‐bonding preassociation in these systems, which brought the methacrylate double bonds within close proximity. The temperature effects on the hydrogen bonding were also investigated. A decrease in the extent of the double‐bond conversion with increasing temperature was observed for the hydrogen‐bonded crosslinker, in contrast to an increased conversion with temperature for hexanediol diacrylate and tricyclodecane dimethacrylate. This was directly indicative of a reduction of hydrogen bonding at elevated temperatures leading to lower conversions. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 4384–4395, 2006     

Patch‐wise local projection stabilized finite element methods for convection–diffusion–reaction problems

In this article, we develop patch‐wise local projection‐stabilized conforming and nonconforming finite element methods for the convection–diffusion–reaction problems. It is a composition of the standard Galerkin finite element method, the patch‐wise local projection stabilization, and weakly imposed Dirichlet boundary conditions on the discrete solution. In this paper, a priori error analysis is established with respect to a patch‐wise local projection norm for the conforming and the nonconforming finite element methods. The numerical experiments confirm the efficiency of the proposed stabilization technique and validate the theoretical convergence rates.     

Incorporation of Titanium(IV) into Sterically Hindered Schiff Bases of Heterocyclic β -Diketones Involving Ketooximes and Glycol as Coligands: Preparation and Structural Considerations

Titanium(IV) complexes of the general formula TiL(OPr ⁱ )₂ [where LH₂ = R CH₃ where R = ─C₆H₅, ─C₆H₄Cl(p)] were prepared by the interaction of titanium isopropoxide with sterically hindered Schiff bases derived from heterocyclic β -diketones in 1:1 molar ratio in dry benzene. The complexes TiL(OPr ⁱ )₂ were used as versatile precursors for the synthesis of other titanium(IV) complexes. Titanium(IV) complexes of the type TiLL'(OPr ⁱ ) (where L'H═R¹R²C═NOH, R¹ = R² = ─CH₃; R¹ = ─CH₃,R² = ─C₆H₅; R¹ = ─COC₆H₅, R² = ─C₆H₅) were synthesized by the reaction of TiL(OPr ⁱ )₂ with ketooximes (L'H) in equimolar ratio in dry benzene. Another type of titanium(IV) complexes having the general formula TiLGH(OPr ⁱ ) (where GH₂═HO─G─OH, G = ─CH₂─CH₂─) have been prepared by the reaction of TiL(OPr ⁱ )₂ with glycol in 1:1 molar ratio in dry benzene. Plausible structures of these new titanium(IV) complexes have been proposed on the basis of analytical data, molecular weight measurements, and spectral studies.     

Some Zirconium(IV) Complexes of Sterically Constrained Sulfur-Containing Schiff Bases of Heterocyclic β -Diketones: Synthetic Strategy and Structural Investigation Based Upon Spectroscopic Studies

Zirconium(IV) Schiff base chelates having the general formula ZrL(OPr ⁱ )₂ [where LH ₂ = R CH ₃ , R = –C ₆ H ₅ , –C ₆ H ₄ Cl(p)] were synthesized by the reaction of Zr(OPr ⁱ )₄.Pr ⁱ OH with sterically constrained sulfur-containing Schiff bases of heterocyclic β -diketones in a 1:1 molar ratio in dry refluxing benzene. The complexes ZrL(OPr ⁱ ) ₂ were used as important precursors for the synthesis of the complexes of the type Zr(L) ₂ . The complexes, Zr(L) ₂ , were prepared by the interaction of precursor ZrL(OPr ⁱ ) ₂ with sterically constrained sulfur-containing Schiff bases of heterocyclic β -diketones in a 1:1 molar ratio in dry benzene. The structures of these zirconium(IV) chelates have been discerned with the help of elemental analyses, physicochemical studies, and spectral [IR and NMR ( ¹ H and ¹³ C)] data. A distorted trigonal bipyramidal and a distorted octahedral geometry may be assigned to zirconium(IV) chelates of the types ZrL(OPr ⁱ ) ₂ and Zr(L) ₂ , respectively.     

Synthesis,Characterization, Thermal,and Antibacterial Studies of Organotin(Iv) Complexes of Indole-3-Butyric Acid and Indole-3-Propionic Acid

Abstract

Six organotin(IV) complexes of type Me₂SnL₂, Bu₂SnL₂, and Ph₃SnL [where L = indole-3-butyric acid (1, 2 and 3) or indole-3-propionic acid (4, 5 and 6)] have been synthesized by the reactions of the corresponding diorganotin(IV) oxide and triphenyltin(IV) hydroxide with respective indole-3-butyric acid (IBH) or indole-3-propionic acid (IPH) in the desired molar ratios of 1:2/1:1. All of the compounds have been characterized by elemental analysis, IR, ¹H NMR, ¹³C NMR, and ¹¹⁹Sn NMR spectroscopy. Thermal studies of all synthesized complexes have been carried out using thermogravimetry (TG) technique under a nitrogen atmosphere. The thermal decompositions for compounds Me₂SnL₂ and Bu₂SnL₂ occurred in two steps, whereas in compounds Ph₃SnL, it exhibited as three steps decomposition and resulted into the formation of pure SnO₂. The complexes were also screened against three gram-positive (Staphylococcus aureus, Staphylococcus epidermidis, and Micrococcus luteus) and three gram-negative (Escherichia coli, Pseudomonas aeruginosa, and Enterobacter aerogenes) bacteria using minimum inhibition concentration (MIC) method, and all of these complexes showed significant antibacterial activity.

[Supplementary materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements for the following free supplemental files: Additional text, tables, and figures.]     

Thermal analysis of new dimethyl/dibutyl tin(IV) compounds with amino acids

Six diorganotin(IV) compounds with amino acids of general formula [(CH₃)₂SnAACl]₂ and [(CH₃CH₂CH₂CH₂)₂SnAACl]₂ (where AA = l-methioninate, l-cysteinate, and l-tryptophanate) were synthesized by reacting dimethyltin(IV) dichloride (M) and dibutyltin(IV) dichloride (B) with l-methionine (M₁) or l-cysteine (C) or l-tryptophan (T) using acetonitrile as solvent and designated as MM₁, MC, MT, BM₁, BC, and BT. The structural characterization of dimethyltin(IV) and dibutyltin(IV) compounds were done using elemental analysis, FT-IR, ¹H-NMR, ¹³C-NMR, and ¹¹⁹Sn-NMR spectroscopy. The thermal properties of the synthesized compounds were studied by thermogravimetric analysis and differential scanning calorimetry techniques in a dynamic atmosphere of nitrogen. The thermal decomposition mechanisms were similar for compounds MM₁, BM₁, MC, BC, and occurred in one step, while in compounds MT and BT it occurred in two consecutive steps. The TG curves of the MT and BT compounds suggest the loss of the ligand (AA) in the first step, with probable formation of a tin oxide R₂SnO intermediate. At the end of the second step free tin is obtained similar to the MM₁, BM₁, MC, BC in accordance with the stoichiometry of the related compounds.