Synthesis,crystal structure and conformational analysis of an unexpected [1,5]dithiocine product of aminopyridine and thiovanillin

The condensation reaction of 2‐mercapto‐3‐methoxybenzaldehyde with 3‐aminopyridine afforded an unexpected N‐alkylated [1,5]dithiocine instead of the N‐salicylideneaniline. The proposed mechanism for this condensation involves a strong intramolecular hydrogen bond between the thiol and the amine groups, leading to a second condensation. The corresponding product, i.e. 4,10‐dimethoxy‐13‐(pyridin‐3‐yl)‐6H,12H‐6,12‐epiminodibenzo[b,f][1,5]dithiocine methanol 0.463‐solvate, C₂₁H₁₈N₂O₂S₂·0.463CH₃OH, was characterized by single‐crystal X‐ray diffraction analysis. The supramolecular structure shows π–π stacking and S…S interactions in the crystal packing. Within the asymmetric unit, two geometries of the N atom are observed. Although a planar geometry should be expected, a pyramidal one is observed due to the crystal packing. The presence of the two geometries was further supported by density functional theory (DFT) calculations that show an electronic energy difference of less than 2 kJ mol^?1 between the two conformers.     

Synthesis of polymer with defined fluorescent end groups via reversible addition fragmentation transfer polymerization for characterizing the conformations of polymer chains in solutions

A new type of chain transfer agent used in reversible addition fragmentation chain transfer (RAFT) polymerization named 9‐anthracenylmethyl (4‐cyano‐4‐(N‐carbazylcarbodithioate) pentanoate) (ACCP) was synthesized with a total yield over 75% by the incorporation of both fluorescent donor and acceptor chromophores. Polymerization of heterotelechelic α,ω end‐labeled dye‐functionalized polystyrene (PS), poly(methyl methacrylate) (PMMA), and poly(n‐butyl methacrylate) (PBMA) with adjustable molecular weights and narrow polydispersity could be conducted by a one‐pot procedure through RAFT polymerization with this bischromophore chain transfer agent. The polymerizations demonstrated “living” controlled characteristics. By taking advantage of the characteristic fluorescence resonance energy transfer (FRET) response between the polymer chain terminals, the variation of chain dimensions in solution from the dilute region to the semidilute region can be monitored by changes in the ratio of the fluorescence intensities of the carbazolyl group to the anthryl group, which lends itself to potential applications in characterizing chain dimensions in solutions for thermodynamic or dynamic studies. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 2413–2420     

Exhaustive search of the configurational space of heat-shock protein 90 with its inhibitor by multicanonical molecular dynamics based dynamic docking

Multicanonical molecular dynamics based dynamic docking was used to exhaustively search the configurational space of an inhibitor binding to the N-terminal domain of heat-shock protein 90 (Hsp90). The obtained structures at 300 K cover a wide structural ensemble, with the top two clusters ranked by their free energy coinciding with the native binding site. The representative structure of the most stable cluster reproduced the experimental binding configuration, but an interesting conformational change in Hsp90 could be observed. The combined effects of solvation and ligand binding shift the equilibrium from a preferred loop-in conformation in the unbound state to an α-helical one in the bound state for the flexible lid region of Hsp90. Thus, our dynamic docking method is effective at predicting the native binding site while exhaustively sampling a wide configurational space, modulating the protein structure upon binding.     

Conformational polymorphism of 3-(azidomethyl)benzoic acid

Three conformational polymorphs of 3-(azidomethyl)benzoic acid, C₈H₇N₃O₂, are reported. All three structures maintain similar carboxylic acid dimers and π–π stacking. Crystal structure analysis and computational evaluations highlight the azidomethyl group as a source of conformational polymorphism, thus having potential implications in the design of solid-state reactions.     

Comonotone approximation with interpolation at the ends on an interval

Let a function f ∈ C[-1, 1], changes its monotonisity at the finite collection Y := {y1,… ,ys} of s points yi ∈ (-1, 1). For each n ≥ N(Y), we construct an algebraic polynomial Pn, of degree ≤ n, which is comonotone with f, that is changes its monotonisity at the same points yi as f, and |f(x)-Pn(x)|≤c(s)ω2(f,(√1-x2)/n), x∈[-1,1],where N(Y) is a constant depending only on Y, c(s) is a constant depending only on s and ω2 (f, t) is the second modulus of smoothness of f.     

Thermodynamic studies on protonation constant of adenosine and guanosine at different temperatures and ionic strengths

Stepwise protonation constants of two purine nucleosides (adenosine and guanosine) were determined at different temperatures (293.15 to 308.15) and various ionic strengths (0.101 to 3.503 mol · kg⁻¹ NaClO₄) using a combination of potentiometric and spectrophotometric method. The thermodynamic parameters (i.e. enthalpy change, ΔH, and entropy change, ΔS) of the protonations were calculated at different temperatures using van’t Hoff and virial equations. The dependence of the protonation constant on ionic strength is modeled by a Debye–Hückel type equation and discussed. Finally, the protonation constants of the nucleosides and the enthalpy change of protonations were determined at zero ionic strength.     

Enhanced conformational sampling method for proteins based on the TaBoo SeArch algorithm: Application to the folding of a mini‐protein,chignolin

The conformational samplings are indispensible for obtaining reliable canonical ensembles, which provide statistical averages of physical quantities such as free energies. However, the samplings of vast conformational space of biomacromolecules by conventional molecular dynamics (MD) simulations might be insufficient, due to their inadequate accessible time‐scales for investigating biological functions. Therefore, the development of methodologies for enhancing the conformational sampling of biomacromolecules still remains as a challenging issue in computational biology. To tackle this problem, we newly propose an efficient conformational search method, which is referred as TaBoo SeArch (TBSA) algorithm. In TBSA, an inverse energy histogram is used to select seeds for the conformational resampling so that states with high frequencies are inhibited, while states with low frequencies are efficiently sampled to explore the unvisited conformational space. As a demonstration, TBSA was applied to the folding of a mini‐protein, chignolin, and automatically sampled the native structure (C_α root mean square deviation < 1.0 Å) with nanosecond order computational costs started from a completely extended structure, although a long‐time 1‐µs normal MD simulation failed to sample the native structure. Furthermore, a multiscale free energy landscape method based on the conformational sampling of TBSA were quantitatively evaluated through free energy calculations with both implicit and explicit solvent models, which enable us to find several metastable states on the folding landscape. © 2015 Wiley Periodicals, Inc.     

Surface Trapping and STM Observation of Conformational Isomers of a Bis(Terpyridine) Ligand from Metallosupramolecular Grids

Tetranuclear Co‐grid complexes incorporating bis‐tridentate ligands, namely 4,6‐bis(2,2′‐bipyrid‐6‐yl)‐2‐phenylpyrimidine, were electrosprayed onto a Au(111) substrate under an ultrahigh vacuum. Fragmentation occurs leaving the ligands in four different conformations. Most ligands are found to form H‐bonded dimers. The most abundant conformer of the ligand on the Au surface is an asymmetric form, which has not been observed before. The present results indicate that the fragmentation of coordination compounds during the deposition process, in principle, allows for surface trapping, identification, and investigation of high energy, out‐of‐equilibrium conformations of the ligand molecules at low temperatures, which otherwise would not be observable.