(Benzo[4, 5]cyclohepta[l, 2-b]thiophen-4-ylidene)acetic Acids: Novel Non-ulcerogenic Antiinflammatory Agents

Compound (Z)- 8a has been found to display interesting antiinflammatory activity. In order to prepare derivatives with a wide variety of substituents in the aromatic part of the molecule, a new synthesis of the key intermediates 9a-g was developed starting from thiophene-3-carboxylic acid ( 11 ) and substituted benzyl bromides. The conversion of 9a-g to 10a-g follows a known procedure. Ketones 10a-g , on reaction with alkyl (dialkoxy-phosphoryl)acetate, followed by isomer separation and alkaline ester hydrolysis, yielded the desired derivatives (Z)- 8a-g and (E)- 8a-g . The biologically most interesting compound (Z)- 8a is currently undergoing clinical trials.     

Study of 169Hf at high rotational frequency

High-spin properties of the nucleus ¹⁶⁹Hf have been studied through the fusion evaporation reaction ⁹⁶Zr(⁷⁶Ge,3n)¹⁶⁹Hf at a beam energy of 310 MeV. The known rotational bands have been extended considerably and 6 new bands have been established, four of which form coupled bands with pronounced M1 connections. Quasiparticle assignments are suggested for the new band structures, and it appears that coupling to vibrational degrees of freedom plays a role. Both coupled bands involve the excitation of quasiprotons. In the region of highest spin, a large alignment gain is interpreted in terms of a mixed crossing where an h _9/2 and an h _11/2 quasiproton provide the two signatures of the aligning configuration. Received: 23 March 2001 / Accepted: 20 September 2001     

High-temperature collisional energy transfer in highly vibrationally excited molecules II: Isotope effects in isopropyl bromide systems

Values for 〈ΔE_down〉, the average downward energy transferred from the reactant to the bath gas upon collision, have been obtained for highly vibrationally excited undeuterated and per-deuterated isopropyl bromide with the bath gases Ne, Xe, C₂H₄, and C₂D₄, at ca. 870 K. The technique of pressure-dependent very low-pressure pyrolysis (VLPP) was used to obtain the data. For C₃H₇Br, the 〈ΔE_down〉 values (cm^?1) are 490 (Ne), 540 (Xe), 820 (C₂H₄), and 740 (C₂D₄), and for C₃D₇Br, 440 (Ne), 570 (Xe), 730 (C₂H₄), and 810 (C₂D₄). The uncertainties in these values are ca. ±10%. The 〈ΔE_down〉 values for the inert bath gases Ne and Xe show excellent agreement with the theoretical predictions of the semi-empirical biased random walk model for monatomic/substrate collisional energy exchange [J. Chem. Phys., 80 , 5501 (1984)]. The relative effects of deuteration of the reactant molecule on 〈ΔE_down〉 also compare favorably with the predictions of this theoretical model. Extrapolated high-pressure rate coefficients (s^?1) for the thermal decomposition of reactant are 10^13.6±0.3 exp(?200 ± 8 kJ mol^?1/RT) for C₃H₇Br and 10^13.9±0.3 exp(?207 ± 8 kJ mol^±1/RT) for C₃D₇Br, which are consistent with previous studies and the expected isotope effect.     

Evaluation of Vanadium(IV) as a Non-radioactive Surrogate for Technetium(IV) by Comparison of Stability Constants for Polyamino Polycarboxylate Ligand Complexation

The stability constants for the Tc(IV) and V(IV) complexation with the polyamino polycarboxylate ligands IDA, NTA, HEDTA and DTPA were determined using liquid–liquid extraction techniques. These stability constants were then used to evaluate the validity of using V(IV) as a chemical analogue for Tc(IV). Results suggest that Tc(IV), as TcOOH⁺, will form β _1?11 complexes with the selected ligands, while V(IV), as VO²⁺, will form β ₁₀₁ complexes. The values for these determined stability constants are (in log₁₀ unit) 10.9 ± 0.1, 11.4 ± 0.1, 14.9 ± 0.1, and 20.1 ± 0.1 for Tc(IV) in 0.5 mol·L^?1 NaCl at 25 °C, for IDA, NTA, HEDTA and DTPA, respectively, they are 9.3 ± 0.1, 11.6 ± 0.2, 15.8 ± 0.1, and 20.8 ± 0.1 for V(IV) in 0.5 mol·L^?1 NaCl at 25 °C, for the same suite of ligands. The incorporation of a hydroxide into the metal ligand complexes formed by Tc(IV) is proposed as the largest factor differentiating the apparent stability constants of Tc(IV) and V(IV). This work shows that V(IV) is a poor analog for Tc(IV); however, despite the differences in complexation mechanism between V(IV) and Tc(IV), V(IV) still appears to have some use for predicting Tc(IV) complexation behavior.     

Reactions of cisplatin hydrolytes, cis-[Pt(15NH3)2(H2O) 2]2+, with N-acetyl-L-cysteine

The reaction of cis-[Pt(¹⁵NH₃)2(H₂O) ₂] ²⁺ (3) with N-acetylcysteine [H₃accys] was investigated in aqueous solution. In this reaction, the ammine in the platinum complex formed was liberated. A mono-dentate sulfur-boundplatinum(II) product cis-[Pt(¹⁵NH₃)₂(H₂O)(H2accys-S)]⁺ (7) and six-membered che-late ring complex cis-[Pt(¹⁵NH₃)₂ (Haccys-S,O)] (8) were formed in solution. The dinuclear sulfur-bridged complex 9, giving a broad peak in ¹⁵N NMR, was also observed, but only present in very tiny amounts. The mass spectrometry (ES-MS) was undertaken from this re action, and the product detected was only the dinuclear sulfur bridged platinum species and species related to it by ammine loss.     

Structural characterization of a copper nitrosyl complex with a {CuNO}10 configuration

The synthesis and characterization of a {CuNO}(10) complex, namely, [Cu(CH(3)NO(2))(5)(NO)][PF(6)](2), has been achieved by the addition of [NO][PF(6)] to copper metal powder in the presence of nitromethane. In the solid state, this complex exhibits a bent Cu-N-O moiety [Cu-N-O = 121.0(3)°] and a long Cu-N bond. This complex readily reacts with mesitylene to form [mesitylene, NO][PF(6)] and [Cu(η(2)-1,3,5-Me(3)C(6)H(3))(2)][PF(6)] by transfer of NO(+) to the mesitylene ring.     

Light-enhanced catalysis by pyridoxal phosphate-dependent aspartate aminotransferase

The mechanisms of pyridoxal 5'-phosphate (PLP)-dependent enzymes require substrates to form covalent "external aldimine" intermediates, which absorb light strongly between 410 and 430 nm. Aspartate aminotransferase (AAT) is a prototypical PLP-dependent enzyme that catalyzes the reversible interconversion of aspartate and α-ketoglutarate with oxalacetate and glutamate. From kinetic isotope effects studies, it is known that deprotonation of the aspartate external aldimine C(α)-H bond to give a carbanionic quinonoid intermediate is partially rate limiting in the thermal AAT reaction. We show that excitation of the 430-nm external aldimine absorption band increases the steady-state catalytic activity of AAT, which is attributed to the photoenhancement of C(α)-H deprotonation on the basis of studies with Schiff bases in solution. Blue light (250 mW) illumination gives an observed 2.3-fold rate enhancement for WT AAT activity, a 530-fold enhancement for the inactive K258A mutant, and a 58600-fold enhancement for the PLP-Asp Schiff base in water. These different levels of enhancement correlate with the intrinsic reactivities of the C(α)-H bond in the different environments, with the less reactive Schiff bases exhibiting greater enhancement. Time-resolved spectroscopy, ranging from femtoseconds to minutes, was used to investigate the nature of the photoactivation of C(α)-H bond cleavage in PLP-amino acid Schiff bases both in water and bound to AAT. Unlike the thermal pathway, the photoactivation pathway involves a triplet state with a C(α)-H pK(a) that is estimated to be between 11 and 19 units lower than the ground state for the PLP-Val Schiff base in water.