Molecular modeling of cytochrome P450 3A4

The three-dimensional structure of human cytochrome P450 3A4 was modeled based on crystallographic coordinates of four bacterial P450s: P450 BM-3, P450cam, P450terp, and P450eryF. The P450 3A4 sequence was aligned to those of the known proteins using a structure-based alignment of P450 BM-3, P450cam, P450terp, and P450eryF. The coordinates of the model were then calculated using a consensus strategy, and the final structure was optimized in the presence of water. The P450 3A4 model resembles P450 BM-3 the most, but the B helix is similar to that of P450eryF, which leads to an enlarged active site when compared with P450 BM-3, P450cam, and P450terp. The 3A4 residues equivalent to known substrate contact residues of the bacterial proteins and key residues of rat P450 2B1 are located in the active site or the substrate access channel. Docking of progesterone into the P450 3A4 model demonstrated that the substrate bound in a 6-orientation can interact with a number of active site residues, such as 114, 119, 301, 304, 305, 309, 370, 373, and 479, through hydrophobic interactions. The active site of the enzyme can also accommodate erythromycin, which, in addition to the residues listed for progesterone, also contacts residues 101, 104, 105, 214, 215, 217, 218, 374, and 478. The majority of 3A4 residues which interact with progesterone and/or erythromycin possess their equivalents in key residues of P450 2B enzymes, except for residues 297, 480 and 482, which do not contact either substrate in P450 3A4. The results from docking of progesterone and erythromycin into the enzyme model make it possible to pinpoint residues which may be important for 3A4 function and to target them for site-directed mutagenesis.     

Strukturen aus AIB2− und BaAl4−analogen Einheiten. I Die Verbindungen Sr4Pd5P5 und Sr2Pd3P3

Structures with AIB₂? and BaAl₄?type Units. I The Compounds Sr₄Pd₅P₅ and Sr₂Pd₃P₃ Sr₄Pd₅P₅ (Cmcm, a = 4.177(1) Å, b = 31.377(5) Å, c = 8.581(2) Å, Z = 4) und Sr₂ Pd₃P₃(Pmmm, a = 4.199(1) Å, b = 4.212(1) Å, c = 34.227(4) Å, Z = 4) have been prepared by heating the elements. Both structures contain exclusively units characteristic for the AIB_2? and BaAl₄?type. The ratio between isolated P-atoms and P₂?pairs is interpreted with an ionic splitting of the formulas.     

The Flipping of CO Ligand Groups in Metal Carbonyl Compounds and its Frequency in Fe(CO)5

It has been proven qualitatively by a number of authors using variable temperature NMR experiments that most metal carbonyl complexes are nonrigid. A quantitative determination of the ligand exchange frequency v_e is often achieved by a line shape analysis or by measurement of the transverse relaxation time T₂ using the Carr-Purcell method. In the case of a “very fast” exchange, however, both methods prove unsuccessful. It is shown in this study that a simultaneous fit of IR or Raman spectra on the one hand and NMR spectra on the other can make possible the determination of v_e for the “very fast” exchange and can also facilitate the determination of v_e in “slow” and “medium” exchange cases considerably. The ligand exchange frequency thus found for Fe(CO)₅, 1.1 × 10¹⁰s^?1, is unexpectedly high; comparison with variable temperature measurements on solid Fe(CO)₅, yields similar energy barriers. A mechanism of exchange closely related to the “Berry mechanism” is proposed. Finally the consequences of this surprisingly large ligand exchange rate are discussed with respect to IR band assignments for molecular “fragments” M(CO)^x (where x=coordination number, and M is a transition metal, typically lanthanoid or actinoid).     

Analysis of NAD(P) and NAD(P)H cofactors by means of imprinted polymers associated with Au surfaces:: A surface plasmon resonance study

Crosslinked films consisting of the acrylamide-acrylamidophenylboronic acid copolymer that are imprinted with recognition sites for β-nicotinamide adenine dinucleotide (NAD⁺), β-nicotinamide adenine dinucleotide phosphate NADP⁺, and their reduced forms (NAD(P)H), are assembled on Au-coated glass supports. The binding of the oxidized cofactors NAD⁺ or NADP⁺ or the reduced cofactors NADH or NADPH to the respective imprinted sites results in the swelling of the polymer films through the uptake of water. Surface plasmon resonance (SPR) spectroscopy is employed to follow the binding of the different cofactors to the respective imprinted sites. The imprinted recognition sites reveal selectivity towards the association of the imprinted cofactors. The method enables the analysis of the NAD(P)⁺ and NAD(P)H cofactors in the concentration range of 1×10⁻⁶ to 1×10⁻³ M. The cofactor-imprinted films associated with the Au-coated glass supports act as active interfaces for the characterization of biocatalyzed transformations that involve the cofactor-dependent enzymes. This is exemplified with the characterization of the biocatalyzed oxidation of lactate to pyruvate in the presence of NAD⁺ and lactate dehydrogenase using the NADH-imprinted polymer film.     

Reaction of carboxamide with Cu2Oisonitrile complex; formation of a new chelated copper(I) complex

Reaction of carboxamides with Cu₂O in the presence of t-butyl isocyanide gave new chelated copper(I) complexes, which probably are formed by the insertion of t-butyl isocyanide into the coppernitrogen bond of copper(I) amide isonitrile complexes, which were initially produced from the carboxamides and Cu₂Ot-butyl isocyanide complex. The same chelated copper(I) complexes were prepared more readily by the reaction of the corresponding N-trimethylsilyl-carboxamides with Cu₂Ot-butyl isocyanide complex. Reactions of the copper(I) complexes thus obtained with alkylating agents, such as alkyl halides, alkyl tosylates and triethyloxonium tetrafluoroborate, also were described.     

二氢茉莉酮酸甲酯的简便合成方法

本文报道二氢茉莉酮酸甲酯的简便合成方法。先由丁二酸和庚酰氯反应得到2-戊基-1,3-环戊二酮(1),再用甲醇醚化1,可得到2-戊基-3-甲氧基-环戊-2-烯酮(2)。2与丙二酸二甲酯反应生成(2-戊基-3-酮-1-环戊烯-)基乙酸甲酮(3)。最后,催化氢化3,便可得到二氢茉莉酮酸甲酯(4)。     

Rapid computer simulation of ESR spectra. Conventional ESR of axially symmetric 14N-nitroxide spin labels

A computer algorithm is presented for the simulation of the effect of molecular tumbling on ESR spectra, and is applied to simulation of the conventional ESR signal (the absorption signal detected at the first harmonic of the modulation frequency and in-phase with the modulation frequency, in the limit of low microwave and modulation power) of axially symmetric ¹⁴N-nitroxide spin labels. The algorithm is extremely fast and is economical in terms of computer memory requirements.     

Extraction and coordination studies of carbamoyl methyl sulfoxide (CMSO) with uranyl bis(β-diketonates). Synthesis and molecular structure of [{UO2(DBM)2}2C6H5CH2SOCH2CONHC6H5]

The carbamoyl methyl sulfoxide compounds of uranyl bis(β-diketonate) of the types [UO₂(DBM)₂CMSO] and [{UO₂(DBM)₂}₂CMSO] (where HDBM = C₆H₅COCH₂COC₆H₅; CMSO = C₆H₅CH₂SOCH₂CONHC₆H₅ or C₆H₅SOCH₂CONⁱPr₂) have been synthesized and characterized by IR and NMR spectroscopic techniques and elemental analysis. Spectral studies show that CMSO acts as a monodentate ligand in [UO₂(DBM)₂CMSO] compounds and bonds through the sulfoxo oxygen atom to the uranyl group. It acts as a bridging bidentate ligand in [{UO₂(DBM)₂}₂CMSO] compounds and bonds through both the sulfoxo and carbamoyl oxygen atoms to two different uranyl groups. The structure of the compound [{UO₂(DBM)₂}₂C₆H₅CH₂SOCH₂CONHC₆H₅] confirms the bridging bidentate mode of coordination for the CMSO ligand. Extraction studies show an enhancement in solvent extraction for the uranyl ion from nitric acid medium when a mixture of thenoyl trifluoroacetone (HTTA) and CMSO was employed.     

Conditional solubility versus pO2− of cerium(III) oxide in molten equimolar NaCl+KCl at 727°C

Reactions between cerium trichloride and oxide ions were studied in NaCl+KCl (1/1) at 1000°K, by potentiometry with a calcia-stabilized zirconia membrane electrode. Titration curves clearly demonstrated the existence of soluble cerium oxychloride (CeO⁺) and precipitated cerium oxide (Ce₂O₃), with respective dissociation constants 10^?11 and 10^?30 (molality scale). The corresponding conditional solubility diagram {log S (Ce^III)=f(pO^2?)} is presented and discussed.     

Synthesis of thiol chelating resins and their adsorption properties toward heavy metal ions

A series of chelating resins, derived from a macroreticular styrene-divinylbenzene (2%) copolymer beads grafted with various poly(ethylene glycols) HO? (? CH₂? CH₂? O? )_n? H(n = 0, 4, 9, 13) and containing thiol groups as chelating functions, have been synthesized in a three-step reaction sequence. The structure of the functionalized resins was confirmed by IR spectrophotometry, elemental analysis, and differential scanning calorimetry. The complexation behavior of these thiol resins was investigated towards Hg(II), Cu(II), and Pb(II) ions in aqueous solution by a batch equilibration technique. The influence of pH on adsorption capacity was also examined. The adsorption values for metal ions' intake followed the order Hg(II) > Cu(II) > Pb(II). The affinity of these polymers towards Hg(II) ions was so high that the total mercury level in the liquid decreased from 20 ppm to below 10 ppb after 2 h of treatment. Polymers can be regenerated by washing with a solution of hydrochloric acid (6N) and 10% by weight of an aqueous solution of thiourea. © 1994 John Wiley & Sons, Inc.