Compressed images for affinity prediction (CIFAP): a study on predicting binding affinities for checkpoint kinase 1 protein inhibitors

Analyses of known protein–ligand interactions play an important role in designing novel and efficient drugs, contributing to drug discovery and development. Recently, machine learning methods have proven useful in the design of novel drugs, which utilize intelligent techniques to predict the outcome of unknown protein–ligand interactions by learning from the physical and geometrical properties of known protein–ligand interactions. The aim of this study is to work through a specific example of a novel computational method, namely compressed images for affinity prediction (CIFAP), in which binding affinities for structurally related ligands in complexes with human checkpoint kinase 1 (CHK1) are predicted. The CIFAP algorithm presented here relates published pIC ₅₀ values of 57 compounds, derived from a thienopyridine pharmacophore, in complexes with CHK1 to their two‐dimensional (2D) electrostatic potential images compressed in orthogonal dimensions. Patterns obtained from the 2D images are then used as inputs in regression and learning algorithms such as support vector regression (SVR) and adaptive neuro‐fuzzy inference system (ANFIS) methods to validate the experimental pIC ₅₀ values. This study revealed that the 2D image pixels in the vicinity of bound ligand surfaces provide more relevant information to make correlations with the empirical pIC ₅₀ values. As compared with ANFIS, SVR gave rise to the lowest root mean square errors and the greatest correlations, suggesting that SVR could be a plausible choice of machine learning methods in predicting binding affinities by CIFAP. Copyright © 2013 John Wiley & Sons, Ltd.     

Bis(p‐nitrobenzoxasulfamato) Complexes of Cadmium(II) and Mercury(II) ‐ Synthesis,Spectra, and X‐Ray Crystal Structures

The reaction of sodium benzoxasulfamate (nbs) with cadmium(II) and mercury(II) sulfate in aqueous solution yield the novel complexes [Cd(nbs)₂(H₂O)₄] (1) and [Hg(nbs)₂(H₂O)₃] ( 2 ), respectively. The complexes were characterized by elemental analyses, IR spectroscopy and X‐ray crystallography. Complex 1 is monomeric and has an octahedral arrangement in which the N‐donor nbs ligands occupy the axial positions, while the water oxygen atoms form the equatorial plane. Complex 2 is polymeric and shows a pentagonal bipyramidal arrangement achieved by the bridging of the HgN₂O₃ units through the weak interaction of the O atoms of the nitro group. The nbs ligands also occupy the axial positions of the pentagonal bipyramid, whereas three water and two nitro oxygen atoms constitute the pentagonal plane. The crystal structure packing in both crystals is achieved by the intermolecular hydrogen bonds involving water hydrogen atoms, nitro and sulfonyl oxygen atoms.     

Electrochemical storage properties of polyaniline-, poly(N-methylaniline)-, and poly(N-ethylaniline)-coated pencil graphite electrodes

Three types of conducting polymers, polyaniline (PANI), poly(N-methylaniline) (PNMA), poly(N-ethylaniline) (PNEA) were electrochemically deposited on pencil graphite electrode (PGE) surfaces characterized as electrode active materials for supercapacitor applications. The obtained films were electrochemically characterized using different electrochemical methods. Redox parameters, electro-active characteristics, and electrostability of the polymer films were investigated via cyclic voltammetry (CV). Doping types of the polymer films were determined by the Mott-Schottky method. Electrochemical capacitance properties of the polymer film coating PGE (PGE/PANI, PGE/PNMA, and PGE/PNEA) were investigated by the CV and potentiostatic electrochemical impedance spectroscopy (EIS) methods in a 0.1 M H₂SO₄ aqueous solution. Thus, capacitance values of the electrodes were calculated. Results show that PGE/PANI, PGE/PNMA, and PGE/PNEA exhibit maximum specific capacitances of 131.78 F g^?1 (≈ 436.50 mF cm^?2), 38.00 F g^?1 (≈ 130.70 mF cm^?2), and 16.50 F g^?1 (≈ 57.83 mF cm^?2), respectively. Moreover, charge-discharge capacities of the electrodes are reported and the specific power (SP) and specific energy (SE) values of the electrodes as supercapacitor materials were calculated using repeating chronopotentiometry.     

A Three—Dimensional Lead(II) Polymer with Bridging Saccharinate and Unusually Coordinated Acetate Ligands — Synthesis,IR Spectra,and Crystal Structure of [Pb(H2O)(μ‐OAc)(μ‐sac)]n

The complex [Pb(H₂O)(μ‐OAc)(μ‐sac)]n with acetate (OAc) and saccharinate (sac) ligands was characterized by IR, elemental analysis and X‐ray crystallography. The mixed‐anion lead(II) complex crystallizes in the triclinic crystal system with the space group of P1¯. The single crystal X‐ray analysis shows that the complex is a coordination polymer in which the lead(II) ions have a highly distorted pentagonal bipyramidal coordination geometry. Lead(II) ions are bridged by carboxylate groups in a zigzag arrangement forming one‐dimensional infinite chains, which are also linked by sac bridges and aromatic π‐π contacts between the adjacent phenyl rings of sac ligands, resulting in a three‐dimensional network. One water molecule coordinates the lead(II) ion and also forms weak hydrogen bonds with the sulfonyl oxygen atoms of the neighboring sac ligands. The sac ligand acts as a bridging ligand through the nitrogen and carbonyl oxygen atoms, while the carboxylate moiety of the acetate ligand shows an unusual (bidentate, and bridging) coordination behaviour, which was observed for the first time in the structure.     

trans‐Bis(diethanolamine‐N,O)bis(saccharinato‐N)cadmium(II)

The structure of the title complex consists of isolated [Cd(C₇H₄NO₃S)₂(C₄H₁₁NO₂)₂] units. The Cd²⁺ cation lies on an inversion centre and is octahedrally coordinated by two N,O‐bidentate diethanol­amine (dea) and two N‐bonded saccharinate (sac) ligands [saccharin is 1,2‐benziso­thia­zol‐3(2H)‐one 1,1‐dioxide]. The dea ligands constitute the equatorial plane of the octahedron, forming two five‐membered chelate rings around the Cd^II ion, while the sac ligands are localized at the axial positions. The Cd—N_sac, Cd—N_dea and Cd—O_dea bond distances are 2.3879 (12), 2.3544 (14) and 2.3702 (13) Å, respectively. The H atoms of the free and coordinated hydroxyl groups of the dea ligands are involved in hydrogen bonding with the carbonyl and sulfonyl O atoms of the neighbouring sac ions, while the amine H atom forms a hydrogen bond with the free hydroxyl O atom. The individual mol­ecules are held together by strong hydrogen bonds, forming an infinite three‐dimensional network.     

Spectrophotometric flow-injection analysis of mercury(II) in pharmaceuticals with p-nitrobenzoxosulfamate

A new, simple and rapid spectrophotometric FI method for the accurate and precise determination of Hg(II) in pharmaceutical preparations has been developed. The method is based on the measuring the decrease of absorbance intensity of p-nitrobenzoxosulfamate (NBS) due to the complexation with Hg(II). The absorption peak of the NBS, which is decreased linearly by addition of Hg(II), occurs at 430 nm in 2×10⁻⁴ mol l⁻¹ HNO₃ as a carrier solution. Optimization of chemical and FI variables has been made. A micro column consisting of several packing materials applied instead of reaction coil was also investigated. A background level of Fe(III) maintained in reagent carrier solution with NBS was found useful for sensitivity and selectivity. Under the optimized conditions, the sampling rate was over 100 h⁻¹, the calibration curve obtained were linear over the range 1-10 μg ml⁻¹, the detection limit was lower than 0.2 μg ml⁻¹ for a 20 μl injection volume, and the precision [S_r=1% at 2 μg ml⁻¹ Hg(II) (n=10)] was found quite satisfactory. Application of the method to the analysis of Hg(II) in pharmaceutical preparations resulted a good agreement between the expected and found values.     

N‐(2‐Hydroxyethyl)ethylenediammonium hydrogenphosphate monohydrate

The title compound, C₄H₁₄N₂O²⁺·HPO₄^2?·H₂O, contains alternating interleaved layers of hydrogenphosphate and N‐(2‐hydroxyethyl)ethyl­enedi­ammonium moieties. The water mol­ecules are associated with channel‐like voids in the structure and a network of hydrogen bonds stabilizes the crystal packing.