Cyanide Bridged Platinum-Iron Complexes as Cisplatin Prodrug Systems: Design and Computational Study

The potential role of cyanide-bridged platinum-iron complexes as an anti-cancer Pt(IV) prodrug is studied. We present design principles of a dual-function prodrug that can upon reduction dissociate and release concurrently six cisplatin units and a ferricyanide anion per prodrug unit. The prodrug molecule is a unique complex of hepta metal centers consisting of a ferricyanide core with six Pt(IV) centers each bonded to the Fe(III) core through a cyano ligand. The functionality of the prodrug is addressed through density functional theory (DFT) calculations.     

A unified theory of thermoviscoplasticity of crystalline solids

A unified theory of thermoviscoplasticity of crystalline solids is presented. In particular it is shown that a thermodynamics for ‘viscoplastic’ materials can be accommodated within the framework of modern mechanics of materials with memory. The basic physical concepts are derived from the consideration of dislocation behaviour of crystalline solids. Relationships of the present approach to several of the existing theories of plasticity are examined.     

Analysis of cyathane-type diterpenoids from Cyathus striatus and Hericium erinaceus by high-resolution MALDI MS imaging

Fungal secondary metabolites in both fruiting bodies and pellets from submerged cultures of basidiomycetes were analyzed by atmospheric pressure matrix-assisted laser desorption/ionization-mass spectrometry imaging at a lateral resolution of 15 μm, a mass resolution of 140,000 at m/z 200 and a mass accuracy of better than 2 ppm. The striatals A, B, C, and D, and a number of erinacine type metabolites were detected in the basidiomycetes Cyathus striatus and Hericium erinaceus, respectively. The two fungi were selected as model species, as they are well-known for efficient production of terpenoid secondary metabolites with interesting biological activities, e.g., antibacterial, fungicidal, cytotoxic properties, and stimulating effects on nerve growth factor synthesis. The localization of metabolites revealed a mostly homogeneous distribution of the striatals in the pellets of C. striatus, while a concentration gradient, increasing to the center, was observed in the pellets of H. erinaceus. A mostly homogeneous distribution of metabolites was also found in the fruiting body of H. erinaceus.     

Nickel(II)-Mediated Reversible Thiolate/Disulfide Conversion as a Mimic for a Key Step of the Catalytic Cycle of Methyl-Coenzyme M Reductase

According to the well-accepted mechanism, methyl-coenzyme M reductase (MCR) involves Ni-mediated thiolate-to-disulfide conversion that sustains its catalytic cycle of methane formation in the energy saving pathways of methanotrophic microbes. Model complexes that illustrate Ni-ion mediated reversible thiolate/disulfide transformation are unknown. In this paper we report the synthesis, crystal structure, spectroscopic properties and redox interconversions of a set of Ni^II complexes comprising a tridentate N₂S donor thiol and its analogous N₄S₂ donor disulfide ligands. These complexes demonstrate reversible Ni^II-thiolate/Ni^II-disulfide (both bound and unbound disulfide-S to Ni^II) transformations via thiyl and disulfide monoradical anions that resemble a primary step of MCR's catalytic cycle.     

Simultaneous high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS-MS) analysis of cyanide and thiocyanate from swine plasma

An analytical procedure for the simultaneous determination of cyanide and thiocyanate in swine plasma was developed and validated. Cyanide and thiocyanate were simultaneously analyzed by high-performance liquid chromatography tandem mass spectrometry in negative ionization mode after rapid and simple sample preparation. Isotopically labeled internal standards, Na¹³C¹⁵N and NaS¹³C¹⁵N, were mixed with swine plasma (spiked and nonspiked), proteins were precipitated with acetone, the samples were centrifuged, and the supernatant was removed and dried. The dried samples were reconstituted in 10 mM ammonium formate. Cyanide was reacted with naphthalene-2,3-dicarboxaldehyde and taurine to form N-substituted 1-cyano[f]benzoisoindole, while thiocyanate was chemically modified with monobromobimane to form an SCN-bimane product. The method produced dynamic ranges of 0.1–50 and 0.2–50 μM for cyanide and thiocyanate, respectively, with limits of detection of 10 nM for cyanide and 50 nM for thiocyanate. For quality control standards, the precision, as measured by percent relative standard deviation, was below 8 %, and the accuracy was within ±10 % of the nominal concentration. Following validation, the analytical procedure successfully detected cyanide and thiocyanate simultaneously from the plasma of cyanide-exposed swine.     

A Facile Diversity‐Oriented Multicomponent One‐Pot Synthesis of 3‐Amino‐6,7‐dihydrobenzo[c]thiophen‐4(5H)‐one Derivatives from α‐Oxo‐N,S‐ketene Acetal

A convenient one‐pot multicomponent method for the preparation of 3‐amino‐6,7‐dihydrobenzo[c]thiophen‐4(5H)‐one derivative has been developed. Reaction of 1,3‐cyclohexanedione and phenyl isothiocynate gave α‐oxo‐N,S‐ketene acetal that were reacted in situ with 2‐chloromethylquniazoline‐4‐one derivatives, in the presence of sodium hydride to afford the target compound in reasonable overall yields.     

Stability-Indicating LC–PDA Method for Determination of Picrosides in Hepatoprotective Indian Herbal Preparations of Picrorhiza kurroa

A liquid chromatography method was developed and validated for the determination of picroside-I and picroside-II in herbal preparations containing Picrorhiza kurroa as one of the ingradients. Resolution of picrosides was achieved on a reversed phase (C-18) endcapped bidentate column by using a mobile phase of acetonitrile: water (25:75 v/v). The detection of picrosides was carried out at 270 nm. The method was validated for precision, accuracy and robustness according to the International Conference on Harmonization (ICH) guidelines and is applicable for the quality control of preparations containing P. kurroa. Analysis of samples in forced degradation proved it to be applicable for stability evaluation. The linear regression analysis data showed good linear relationship (r ² = 0.9999 ± 0.0010 for picroside-I and 0.9997 ± 0.0012 for picroside-II) in the concentration range of 0.4–4.0 μg. The limit of detection and quantification for picroside-I and picroside-II were recorded to be 28.1 and 73.1 ng and 85.2 and 221.5 ng, respectively. Satisfactory recovery results were observed from the herbal preparations (97.5–100.5%). Intra- and inter- day precision of the method was acceptable, with relative standard deviation (%RSD) values in the range of 0.04–1.16% and 0.03–0.27%, respectively.