Effect of a Phosphazene Base on the Diastereoselectivity of Addition of alpha-Sulfonyl Carbanions to Butyraldehyde and Isopropylideneglyceraldehyde

The effect of tBuP4, a strong and cation-free base, on the yield and diastereoselectivity of additions of thus formed "naked" alpha-sulfonyl carbanions to achiral butyraldehyde and chiral isopropylideneglyceraldehyde was studied. It has been found that with tBuP4 a reasonable yield ( approximately 55%) and a slightly better diastereoselectivity (72% of the anti diastreomer) are obtained with achiral and nonfunctionalized butyraldehyde while with isopropylideneglyceraldehyde the use of tBuP4 allowed us to greatly increase the yields (up to 95-100%) and the diastereoselectivities (83-89% of a single diastereomer over the four possible diastereomers). It was also shown that the extra oxygen atom in the alpha-position plays a determinant role in this effect.     

A homoleptic molybdenum(IV) enolate complex: synthesis, molecular and electronic structure, and NCN group transfer to form a terminal cyanoimide of molybdenum(VI)

A monomeric molybdenum(IV) tetrakis enolate complex Mo(OC[Ad]Mes)(4), 1, where Ad = 2-adamantylidene and Mes = 2,4,6-Me(3)C(6)H(2), has been synthesized and characterized structurally by X-ray diffraction, chemically through NCN group-transfer reactivity, and computationally to investigate the origins of the observed structure that is intermediate between tetrahedral and square planar. No prior examples of Mo(OR)(4) have been structurally characterized despite having been the subject of both experimental and theoretical interest. Complex 1 has a singlet ground state and thus a metal-based lone pair of electrons. The latter has been visualized with the aid of the electron localization function (ELF) and appears as a two-bladed propeller with D(2)(d)() symmetry. Complex 1 makes a simple 1:1 adduct with t-BuNC that is trigonal bipyramidal with an axial isocyanide as demonstrated by X-ray crystallography. This trigonal bipyramidal 1:1 adduct has a triplet ground state and provides a model for the way in which 1 interacts with NCN group donor dbabhCN prior to NCN group transfer to form the terminal cyanoimide complex 1-NCN. The calculated Mo-N bond dissociation enthalpy for 1-NCN is 104 kcal mol(-1), 30 kcal mol(-1) greater than that for the corresponding dissociation of NCN from cyanophosphiniminato NCNPMe(3).     

Computer-aided drug design: A free energy perturbation study on the binding of methyl-substituted pterins and N5-deazapterins to dihydrofolate reductase

Summary Molecular dynamics simulation and free energy perturbation techniques have been used to study the relative binding free energies of 8-methylpterins and 8-methyl-N5-deazapterins to dihydrofolate reductase (DHFR). Methyl-substitution at the 5, 6 and 7 positions in the N-heterocyclic ring gives rise to a variety of ring substituent patterns and biological activity: several of these methyl derivatives of the 8-methyl parent compounds (8-methylpterin and 8-methyl-N5-deazapterin) have been identified as substrates or inhibitors of vertebrate DHFR in previous work. The calculated free energy differences reveal that the methyl-substituted compounds are thermodynamically more stable than the primary compounds (8-methylpterin and 8-methyl-N5-deazapterin) when bound to the enzyme, due largely to hydrophobic hydration phenomena. Methyl substitution at the 5 and/or 7 positions in the 6-methyl-substituted compounds has only a small effect on the stability of ligand binding. Furthermore, repulsive interactions between the 6-methyl substituent and DHFR are minimal, suggesting that the 6-methyl position is optimal for binding. The results also show that similarly substituted 8-methylpterins and 8-methyl-N5-deazapterins have very similar affinities for binding to DHFR. The computer simulation predictions are in broad agreement with experimental data obtained from kinetic studies, i.e. 6,8-dimethylpterin is a more efficient substrate than 8-methylpterin and 6,8-dimethyl-N5-deazapterin is a better inhibitor than 8-methyl-N5-deazapterin.     

Molybdenum chalcogenobenzimidato complexes: radical synthesis and nitrile extrusion via beta-EPh (E = S, Se, and Te) elimination

Molybdenum chalcogenobenzimidates of formula (Ph[PhE]C=N)Mo(N[t-Bu]Ar)(3) (Ar = 3,5-C(6)H(3)Me(2)) have been obtained by treatment of Mo(N[t-Bu]Ar)(3) sequentially with benzonitrile and 0.5 equiv of PhEEPh (E = S, Se, and Te). Molecular structure determinations have been carried out for the S and Se variants. The Te variant extrudes PhCN forming structurally characterized (PhTe)Mo(N[t-Bu]Ar)(3) with facility assessed via stopped-flow kinetic measurements, while the Se and S analogues exhibit increasing stability. Quantum chemical calculations and solution calorimetry have been employed as an aid to interpretation of the PhCN extrusion reaction.     

Engineering Bisquinolinium/Thiazole Orange Conjugates for Fluorescent Sensing of G‐Quadruplex DNA

Lighting up : A G‐quadruplex‐specific fluorescent probe was designed combining the specificity of the pyridodicarboxamide motif for guanine quadruplexes and the fluorescence properties of thiazole orange. While the assembly of the two partners through a flexible linker leads to a nonselective probe, merging them in a single, rigid scaffold leads to a dye that elicits the properties required for G‐quadruplex sensing.