PHOTOLYTIC REARRANGEMENT OF METRONIDAZOLE TO 1-HYDROXYETHYL-2-METHYL-4-HYDROXYIMINO-5-OXO-IMIDAZOLE AND THE FORMATION OF COPPER COMPLEXES OF THESE COMPOUNDS

Abstract— A labile intermediate in the photolytic rearrangement of the antibacterial drug, metronidazole, was identified by isolating the product of photolysis of metronidazole benzoate in methanol. The intermediate, 1-hydroxyethyl-2-methyl-4-hydroxyimino-5-oxo-imidazole, was shown to act as a bidentate chelating agent for copper(II) ions, whereas metronidazole forms a weak monodentate complex. The intermediate may be relevant to the bioactivation mechanism of metronidazole.     

Photochemical reactions of Ru3(CO)12 involving metalmetal bond fission

Photolysis of Ru₃(CO)₁₂ in the presence of donor ligands rapidly produces monomeric ruthenium species.     

Formation of the unusual alkynyl carboxamide complex, C2H5N(H)C(O)CC[Co2(CO)6]CCo3(CO)9

The reaction of the cluster complex HCC[Co₂(CO)₆]CCo₃(CO)₉ with (or without) BrCCo₃(CO)₉ under Cadiot-Chodkiewicz coupling conditions gave the unusual alkynyl carboxamide complex C₂H₅N(H)C(O)CC[Co₂(CO)₆]CCo₃(CO)₉ rather than a coupled product containing two tricobalt cluster units. Steric demands imposed by the Co₃ cluster allow attack at the least hindered alkyne carbon and stabilise the formed ynamine, so allowing subsequent CO insertion. The product has been characterised by X-ray crystallography.     

Reactions of N-heterocyclic carbenes (NHCs) with one-electron oxidants: possible formation of a carbene cation radical

One-electron oxidation of N-heterocyclic carbenes (NHCs) has been carried out using oxidising agents such as tetracyanoethylene (TCNE) and ferrocenium [Cp(2)Fe](+); the formation of carbene radical cations is postulated.     

Structural mining: self-consistent design on flexible protein-peptide docking and transferable binding affinity potential

A flexible protein-peptide docking method has been designed to consider not only ligand flexibility but also the flexibility of the protein. The method is based on a Monte Carlo annealing process. Simulations with a distance root-mean-square (dRMS) virtual energy function revealed that the flexibility of protein side chains was as important as ligand flexibility for successful protein-peptide docking. On the basis of mean field theory, a transferable potential was designed to evaluate distance-dependent protein-ligand interactions and atomic solvation energies. The potential parameters were developed using a self-consistent process based on only 10 known complex structures. The effectiveness of each intermediate potential was judged on the basis of a Z score, approximating the gap between the energy of the native complex and the average energy of a decoy set. The Z score was determined using experimentally determined native structures and decoys generated by docking with the intermediate potentials. Using 6600 generated decoys and the Z score optimization criterion proposed in this work, the developed potential yielded an acceptable correlation of R(2) = 0.77, with binding free energies determined for known MHC I complexes (Class I Major Histocompatibility protein HLA-A(*)0201) which were not present in the training set. Test docking on 25 complexes further revealed a significant correlation between energy and dRMS, important for identifying native-like conformations. The near-native structures always belonged to one of the conformational classes with lower predicted binding energy. The lowest energy docked conformations are generally associated with near-native conformations, less than 3.0 Angstrom dRMS (and in many cases less than 1.0 Angstrom) from the experimentally determined structures.     

Gas-phase electron diffraction determination of the molecular structure of perfluoro(methyloxirane)

The molecular geometry of perfluoro(methyloxirane) has been studied using gas-phase electron diffraction data, effective least-squares refinement of the structure being achieved with the aid of constraints to limit the number of variable parameters. With the CCF₃ bond constrained to be 0.078 Å longer than the ring CC, the refined bond- length values CF (av.) = 1.323(2), CO (av.) = 1.410(8), and CC (ring) = 1.467(7) Å ($\text{r}$_g values, with e.s.d. in parentheses) were obtained; the angles between ring bonds and substituent CF bonds were CCF (av.) 121(1) and OCF (av.) 114(1)^o, the corresponding parameters involving the bulkier CCF₃ fragment being larger by 3^o in each case [∠CCCF₃ 124(1)^o∠OCCF₃ 117(2)^o]. The remaining refined parameters were ∠CCF(of CF₃) = 110.6(4)^o and τ , a torsion angle defining the orientation of the CF bonds of the CF₃ group with respect to ring bonds, = 29(2)^o. Dependent bond angles possessed the values 62.7 (COC), 58.7 [OCC (ring)], 108.3 [FCF (CF₃ group)], 114 [FCF (ring CF₂)], and 111^o (FCCF₃).