Histone deacetylase inhibitors: structure-based modeling and isoform-selectivity prediction

An enhanced version of comparative binding energy (COMBINE) analysis, named COMBINEr, based on both ligand-based and structure-based alignments has been used to build several 3-D QSAR models for the eleven human zinc-based histone deacetylases (HDACs). When faced with an abundance of data from diverse structure-activity sources, choosing the best paradigm for an integrative analysis is difficult. A common example from studies on enzyme-inhibitors is the abundance of crystal structures characterized by diverse ligands complexed with different enzyme isoforms. A novel comprehensive tool for data mining on such inhomogeneous set of structure-activity data was developed based on the original approach of Ortiz, Gago, and Wade, and applied to predict HDAC inhibitors' isoform selectivity. The COMBINEr approach (apart from the AMBER programs) has been developed to use only software freely available to academics.     

Bis(2‐amino‐1H‐benzimidazol‐3‐ium) tetrakis(μ‐but‐2‐enoato)‐κ4O:O′;κ3O,O′:O;κ3O:O,O′‐bis[bis(but‐2‐enoato‐κ2O,O′)holmium(III)]

The title ionic compound, (C₇H₈N₃)₂[Ho₂(C₄H₅O₂)₈], is constructed from two almost identical independent centrosymmetric anionic dimers balanced by two independent 2‐amino‐1H‐benzimidazol‐3‐ium (Habim⁺) cations. The asymmetric part of each dimer is made up of one Ho^III cation and four crotonate (crot or but‐2‐enoate) anions, two of them acting in a simple η²‐chelating mode and the remaining two acting in two different μ₂:η² fashions, viz. purely bridging and bridging–chelating. Symmetry‐related Ho^III cations are linked by two Ho—O—Ho and two Ho—O—C—O—Ho bridges which lead to rather short intracationic Ho...Ho distances [3.8418 (3) and 3.8246 (3) Å]. In addition to the obvious Coulombic interactions linking the cations and anions, the isolated [Ho₂(crot)₈]²⁻ and Habim⁺ ions are linked by a number of N—H...O hydrogen bonds, in which all N—H groups of the cation are involved as donors and all (simple chelating) crot O atoms are involved as acceptors. These interactions result in compact two‐dimensional structures parallel to (110), which are linked to each other by weaker π–π contacts between Habim⁺ benzene groups.     

catena‐Poly[copper(II)‐μ‐l‐tyrosyl‐l‐leucinato]

In the title compound, [Cu(C₁₅H₂₀N₂O₄)]_n, the copper(II) coordination is square planar. The anionic l ‐tyrosyl‐l ‐leucinate ligand binds in an N,N′,O‐tridentate mode to one Cu^II cation on one side and in an O‐monodentate mode to a second Cu^II cation on the other side, thus defining –Cu—O—C—O—Cu′– chains which run along the a axis. These chains are held together by a strong hydrogen bond involving the hydroxy H atom.     

catena‐Poly­[[bis­(hexa­fluoro­acetyl­acetonato‐κ2O,O′)­zinc(II)]‐μ‐4,4′‐bi­pyridine‐κ2N:N′]

The structure of the title compound, catena‐poly[[bis(1,1,1,5,5,5‐hexafluoropentane‐2,4‐dionato‐κ²O,O′)zinc(III)]‐μ‐4,4′‐bipyridine‐κ²N:N′], [Zn(C₅HF₆O₂)₂(C₁₀H₈N₂)]_n, con­sists of polymeric chains, running in two perpendicular directions, organized as planes normal to the tetragonal axis. The elemental unit of the chains is the zinc(II) coordination polyhedron bisected by a twofold symmetry axis, and thus only half of the unit is independent. The octahedral coordination geometry of the metal centre is composed of two oxy­gen‐chelating (symmetry‐related) hexa­fluoro­acetyl­acetonate groups and two translationally related 4,4′‐bi­pyridine groups, which act as connecting agents in the polymer structure. The stabilization of this architecture of chains and planes is associated with a number of weak C—H⋯O and C—H⋯F hydrogen bonds.     

The Flow Lab: A Simple Activity for Generating NOS Principles

While there is near universal agreement within the science education community that a strong understanding of nature of science (NOS) ‐ both as a student goal and a teacher attribute ‐ is critical, we still struggle with how to achieve these aims. Barriers range from pragmatic logistics to fundamental curricular tensions. In this paper, we share a classroom activity designed to aid in the learning of key NOS principles that we have found constructive. We discuss the basic activity, connections to science studies literature, and opportunities for explicit reflection on nature of science.     

Heterobimetallic Re–Pd,Re–Au and Re–Cu complexes derived from diphenylphosphino cyrhetrene: Synthesis and X-ray structure

Diphenylphosphinecyrhetrene ligand (η⁵-C₅H₄PPh₂)Re(CO)₃ (1) reacts with 1 equiv. of PdCl₂(NCPh)₂ to form, after workup, the square-planar trans-[(η⁵-C₅H₄PPh₂)Re(CO)₃]PdCl₂(NCMe) (2). Similarly, reaction of 1 with (tetrahydrothiophene)AuCl produces, in excellent yield, the bimetallic complex [(η⁵-C₅H₄PPh₂)Re(CO)₃]AuCl (3) with a linear P–Au–Cl moiety. From the reaction of 2 equiv. of 1 with CuBr(SMe₂) the planar-trigonal complex [(η⁵-C₅H₄PPh₂)Re(CO)₃]₂CuBr (4) was obtained. ³¹P NMR and X-ray crystallography demonstrate, for the three cases, that (η⁵-C₅H₄PPh₂)Re(CO)₃ acts as a monodentate ligand. The structural parameters of the bimetallic complexes are compared with related diphenylphosphinoferrocene metal complexes, described in the literature.     

The contributions of Carl Friedrich Gauss to geomagnetism

The three areas of geomagnetism in which Gauss made great contributions were those related to the absolute measurement of the field, the analysis in terms of spherical harmonics, and the organization and equipping of magnetic observatories. His approaches and accomplishments in these areas are examined in some detail. Because of the insufficiency of observations over the globe at the time he worked, many of the investigations which he proposed on the basis of the spherical harmonic analysis had to await later workers. These include the quantitative separation of internal and external sources, the effect of the earth's ellipsoidal shape, the possible non-vanishing of the constant term in the expression for the potential and the possible existence of a non-potential portion of the field. The results of these later investigations are outlined.     

Relative transition probability measurements in the A-X and B-X systems of CH

Relative Einstein emission coefficients have been measured for transitions from the ν′ = 0 and 1 levels in the A²Δ?X²Π and B²Σ^-?X²Π systems of the CH radical. The measurements were made in an atmospheric pressure methane-air flame, and the results are compared with theoretical calculations.