Leveraging γ‐Glutamyl Transferase To Direct Cytotoxicity of Copper Dithiocarbamates against Prostate Cancer Cells

A prodrug approach is presented to direct copper‐dependent cytotoxicity to prostate cancer cells. The prochelator GGTDTC requires activation by γ‐glutamyl transferase (GGT) to release the metal chelator diethyldithiocarbamate from a linker that masks its thiol reactivity and metal binding properties. In vitro studies demonstrated successful masking of copper binding as well as clean liberation of the chelator by GGT. GGTDTC was stable to non‐specific degradation when incubated with a series of prostate cancer and normal cell lines, with selective release of diethyldithiocarbamate only occurring in cells with measurable GGT activity. The antiproliferative efficacy of the prochelator correlated with cellular GGT activity, with 24 h inhibitory concentrations ranging from 800 nm in prostate cancer lines 22Rv1 and LNCaP to over 15 μm in normal prostate PWR‐1E cells. These findings underscore a new strategy to leverage the amplified copper metabolism of prostate cancer by conditional activation of a metal‐binding pharmacophore.     

Total synthesis of carbazole alkaloids

A Suzuki-Miyaura cross coupling, followed by triphenylphosphine mediated Cadogan reductive cyclization sequence provided efficient access to a series of carbazole alkaloids.In the present work, this approach was applied to the total synthesis of mukonine, clauszoline K, koenoline, murrayanine, murrayafoline A, mukoeic acid, glycoborine, glycozolicine, mukolidine, mukoline, glycozoline, 3-methoxy-9H-carbazole-1-carboxylic acid methyl ester, (3-methoxy-9H-carbazol-1-yl)-methanol, 3-methoxy-9H-carbazole-1-carbaldehyde, 3-methoxy-9H-carbazole-1-carboxylic acid, 2-methyl-9H-carbazole and nonsteroidal anti-inflammatory drug (NSAID) carprofen and its derivatives.     

Novel Copolymers of Styrene. Alkyl and Alkoxy Ring-Substituted 2-Phenyl-1,1-dicyanoethylenes

Novel copolymers of trisubstituted ethylene monomers, alkyl and alkoxy ring-substituted 2-phenyl-1,1-dicyanoethylenes, RC₆H₄CH=C(CN)₂ (where R is 2-ethyl, 4-i-propyl, 4-butyl, 4-i-butyl, 4-t-butyl, 2-ethoxy, and 4-hexyloxy) and styrene were prepared at equimolar monomer feed composition by solution copolymerization in the presence of a radical initiator (ABCN) at 70°C. The composition of the copolymers was calculated from nitrogen analysis, and the structures were analyzed by IR, ¹H and ¹³C-NMR. The order of relative reactivity (1/r ₁) for the monomers is 4-t-butyl (1.45) > 4-i-propyl (1.38) > 2-ethyl (1.37) > 4-hexyloxy (1.33) > 4-i-butyl (1.24) > 2-ethoxy (1.13) > 4-butyl (1.04). High T _g of the copolymers, in comparison with that of polystyrene) indicates a substantial decrease in chain mobility of the copolymer due to the high dipolar character of the trisubstituted ethylene monomer unit. Decomposition of the copolymers in nitrogen occurred in two steps, first in the 200–500°C range with residue (1–10% wt.), which then decomposed in the 500–800°C range.     

Sarcosinium tartrate

In the title compound, C₃H₈NO₂⁺·C₄H₅O₆⁻, the sarcosinium cation and semi-tartrate anion are held together by a three-dimensional network of O—H⃛O, N—H⃛O and C—H⃛O hydrogen bonds. The structure may be described as an inclusion compound with the semi-tartrate anion as the host and the sarcosinium cation as the guest.     

Effect of size of metal ion on MS4N2 chromophore: Synthesis,spectral and single crystal X-ray structural studies on (2,2′-bipyridine)bis(N-cyclohexyl-N-methyldithiocarbamato)M(II) (M = zinc,cadmium)

Isomorphous complexes [Zn(S₂CN(Me)Cy)₂(bipy)] (1) and [Cd(S₂CN(Me)Cy)₂(bipy)] (2) (where Cy(Me)NCS₂⁻ = N-cyclohexyl-N-methyldithiocarbamate anion and bipy = 2,2′-bipyridine) have been synthesised. Their structures and spectroscopic properties have been studied by IR, ¹H and ¹³C NMR spectroscopy and single crystal X-ray analysis. IR spectrum of the complexes show the contribution of thioureide form to the structures. ¹H NMR spectra of the complexes showed the desheilding of methyl protons and H-1 of cyclohexyl group on complexation. The downfield shift of N¹³CS₂, methyl carbon and C-1 of cyclohexyl group carbon signals for 2 (205.5, 36.7 and 64.4 ppm) from the chemical shift value of 1 (204.2, 35.6 and 63.1 ppm) is attributed to the movement of more electron density from dithiocarbamate towards cadmium. Single crystal X-ray structures of 1 and 2 indicate that the central metal atom is in a distorted octahedral environment for both complexes. The presence of added 2,2′-bipyridine ligand in the coordination sphere of M(S₂CN(Me)Cy)₂ increases Zn–S distances and decreases S–Zn–S angles in 1 and slightly increases Cd–S distances in 2. S–Cd–S angles are not affected. This is due to the relatively larger size of the cadmium ion compared to zinc ion which alleviates the strain involved in transformation from tetrahedral to octahedral.     

Excess electron and lithium atom solvation in water clusters at finite temperature: an ab initio molecular dynamics study of the structural, spectral, and dynamical behavior of (H2O)6- and Li(H2O)6

The roles of hydrogen bonds in the solvation of an excess electron and a lithium atom in water hexamer cluster at 150 K have been studied by means of ab initio molecular dynamics simulations. It is found that the hydrogen bonded structures of (H(2)O)(6)(-) and Li(H(2)O)(6) clusters are very different from each other and they dynamically evolve from one conformer to other along their simulation trajectories. The populations of the single acceptor, double acceptor, and free type water molecules are found to be significantly high unlike that in pure water clusters. Free hydrogens of these type of water molecules primarily capture the unbound electron density in these clusters. It is found that the binding motifs of the free electron evolve with time and the vertical detachment energy of (H(2)O)(6)(-) and vertical ionization energy of Li(H(2)O)(6) also change with time. Assignments of the observed peaks in vibrational power spectra are done, and we found direct correlations between the time-averaged population of water molecules in different hydrogen bonding states and the spectral features. The dynamical aspects of these clusters have also been studied through calculations of time correlations of instantaneous stretch frequencies of OH modes which are obtained from the simulation trajectories through a time series analysis.     

l‐Prolinium tartrate

In the title salt, C₅H₁₀NO₂⁺·C₄H₅O₆^?, proline exists as a cation and the tartaric acid as a semi‐tartrate anion. The semi‐tartrate ions form hydrogen‐bonded strings along the c axis. These strings are interconnected through the proline mol­ecules, forming a layered network parallel to the bc plane. The proline mol­ecules, however, do not directly interact among themselves, except for a weak C—H?O hydrogen bond.     

First principles study and database analyses of structural preferences for sodium ion (Na+) solvation and coordination

Extensive computations were performed on aqueous clusters of monovalent sodium cation [Na⁺(H₂O) _n ; (n = 1–20)] using MP2/cc-pVTZ and density functional theory. The structure, energy, and coordination number (CN) preference of a large number of competing conformations of different complexes have been explored. For complexes up to n = 12, the CN 4 is most preferred while 5, 6 CNs are favored in case of larger complexes containing up to 20 water molecules. These results are in very good agreement with experimental observations. The strength of hydrogen bonding among the waters coordinated to the Na⁺ ion is found to play a major role in the stability of the complexes. The varying preferences for CN of Na⁺ ion were explored by screening two important databases: Protein Databank and Cambridge Structural Database. A linear correlation is observed between the M (Metal)–O distance and the charge on metal ion in complex with the increase in CN of metal ion.