Synthesis,molecular characterisation,and in vivo study of platinum(IV) coordination compounds against B16 mouse melanoma tumours

A novel platinum(IV) coordination compound with 6-mercaptopurine (6-Hmp) has been synthesised and characterised by IR and NMR spectroscopy. Spectroscopic parameters indicate the presence of two chelate (S-6, N-7) monodeprotonated ligands and two chloride ions in the coordination sphere of [PtCl₂(6-mp)₂] · H₂O (I). Two Pt(IV) coordination compounds, [PtCl₂(6-mp)₂] · H₂O (I) and [PtCl₄(dbtp)₂] (II), were used in the in vivo test against B16 mouse melanoma tumours. Cytotoxic activity of compound II against the tumour cells was found to be high (LC₁₀ = 2.6 μM, LC₅₀ = 17.0 μM, LC₉₀ = 58.0 μM) compared to that of cisplatin.     

Studies on the chemistry of thienoannelated O,N‐ and S,N‐containing heterocycles. 25. Synthesis of new imidazolyl and pyrazolyl derivatives of thiophene as inhibitors of nitric oxide synthase

Some novel imidazolyl and pyrazolyl thiophene derivatives were synthesized. Different substituted N‐containing heterocycles were chosen with the aim of enhancing the activity or selectivity of the products towards inhibition of one of the three isoforms of nitric oxide synthase. One series of substances was prepared by substitution reactions of 3‐bromo‐2‐nitrothiophene with various heterocycles. In the other series introduction of a second heterocyclic substituent to pyrazolylthiophene compounds was attempted.     

2‐Chloro‐4,5‐dihydroimidazole,Part X. Revisiting route to N‐heteroarylimidazolidin‐2‐ones

The ureidation reactions of 2‐ and 4‐picoline N‐oxides with 2‐chloro‐4,5‐dihydroimidazole are described. A mechanism of novel thioureidation reaction of 4‐picoline N‐oxide with 2‐(4,5‐dihydro‐1H‐imidazol‐2‐ylthioxy)‐4,5‐dihydro‐1H‐imidazole is proposed. Structural assignment is confirmed by ¹H and ¹³C nmr as well as by X‐ray crystallography.     

One site fits both: A model for the ternary complex of folate + NADPH in R67 dihydrofolate reductase, a D2 symmetric enzyme

R67 dihydrofolate reductase (DHFR) is a novel enzyme that confers resistance to the antibiotic trimethoprim. The crystal structure of R67 DHFR displays a toroidal structure with a central active-site pore. This homotetrameric protein exhibits 222 symmetry, with only a few residues from each chain contributing to the active site, so related sites must be used to bind both substrate (dihydrofolate) and cofactor (NADPH) in the productive R67 DHFR?NADPH?dihydrofolate complex. Whereas the site of folate binding has been partially resolved crystallographically, an interesting question remains: how can the highly symmetrical active site also bind and orient NADPH for catalysis? To model this ternary complex, we employed DOCK and SLIDE, two methods for docking flexible ligands into proteins using quite different algorithms. The bound pteridine ring of folate (Fol I) from the crystal structure of R67 DHFR was used as the basis for docking the nicotinamide-ribose-P_i (NMN) moiety of NADPH. NMN was positioned by both DOCK and SLIDE on the opposite side of the pore from Fol I, where it interacts with Fol I at the pore's center. Numerous residues serve dual roles in binding. For example, Gln 67 from both the B and D subunits has several contacts with the pteridine ring, while the same residue from the A and C subunits has several contacts with the nicotinamide ring. The residues involved in dual roles are generally amphipathic, allowing them to make both hydrophobic and hydrophilic contacts with the ligands. The result is a `hot spot' binding surface allowing the same residues to co-optimize the binding of two ligands, and orient them for catalysis.     

Finding transition states using reduced potential-energy surfaces

 We propose a method to locate saddle points that is based on the interplay between the driving coordinate and the restricted quasi-Newton algorithm. The method locates the transition state using a reduced potential-energy surface. The reduced potential-energy surface is characterized by the set of driving coordinates. The proposed algorithm starts at a point on the surface that is slightly perturbed from either reactant or product and, in principle, converges to the transition state. Finally we give a special type of update Hessian matrix formula that should be applied in optimizations carried out on reduced potential-energy surfaces. Received: 29 September 2000 / Accepted: 3 January 2001 / Published online: 3 April 2001     

荧光猝灭法测定痕量砷（Ⅲ）

根据在稀盐酸介质中,碘酸钾可与As(Ⅲ）发生氧化还原反应生成I2,I2与荧光试剂吡咯红Y作用,使其荧光猝灭,提出了一种新的测定痕量As(Ⅲ）的荧光分析法。该方法的线性范围为24.0-248μg/L,检出限为14.1μg/L,方法用于自来水、尿液、血清及合成样中痕量As(Ⅲ）的测定,均获得满意结果。     

Uranium assay and trace element analysis of the fourth collaborative material exercise samples by the modified Davies-Gray method and the ICP-MS/OES techniques

Journal of Radioanalytical and Nuclear Chemistry - An international group of laboratories participating in CMX-4 subjected three samples to comparative nuclear forensic analysis using uranium assay...