Facile S(N)2 reaction in protic solvent: quantum chemical analysis

We study the effects of protic solvent (water, methanol, ethanol, and tert-butyl alcohol) and cation (Na+, K+, Cs+) on the unsymmetrical SN2 reaction X- + RY --> RX + Y- (X = F, Br; R = CH3,C3H7;Y = Cl, OMs). We describe a series of calculations for the S(N)2 reaction mechanism under the influence of cation and protic solvent, presenting the structures of pre- and postreaction complexes and transition states and the magnitude of the activation barrier. An interesting mechanism is proposed, in which the protic solvent molecules that are shielded from the nucleophile by the intervening cation act as a Lewis base to reduce the unfavorable Coulombic influence of the cation on the nucleophile. We predict that the reaction barrier for the S(N)2 reaction is significantly lowered by the cooperative effects of cation and protic solvent. We show that the cation and protic solvent, each of which has been considered to retard the SN2 reactivity of the nucleophile, can accelerate the reaction tremendously when they interact with the fluoride ion in an intricate, combined fashion. This alternative S(N)2 mechanism is discussed in relation to the recently observed phenomenal efficiency of fluorination in tert-alcohol media [Kim, D. W.; et al. J. Am. Chem. Soc. 2006, 128, 16394].     

Synthesis,Characterization, Self‐Assembly,Gelation, Morphology and Computational Studies of Alkynylgold(III) Complexes of 2,6‐Bis(benzimidazol‐2′‐yl)pyridine Derivatives

A novel class of alkynylgold(III) complexes of the dianionic ligands derived from 2,6‐bis(benzimidazol‐2′‐yl)pyridine (H₂bzimpy) derivatives has been synthesized and characterized. The structure of one of the complexes has also been determined by X‐ray crystallography. Electronic absorption studies showed low‐energy absorption bands at 378–466 nm, which are tentatively assigned as metal‐perturbed π–π* intraligand transitions of the bzimpy^2? ligands. A computational study has been performed to provide further insights into the nature of the electronic transitions for this class of complexes. One of the complexes has been found to show gelation properties, driven by π–π and hydrophobic–hydrophobic interactions. This complex exhibited concentration‐ and temperature‐dependent ¹H NMR spectra. The morphology of the gel has been characterized by transmission electron microscopy (TEM) and scanning electron microscopy (SEM).     

Random styrenic copolymers with pendant pyrene moieties: Synthesis and applications in organic field‐effect transistor memory

Three random copolymers comprised pendant styrene and 4‐(1‐pyrenyl)‐styrene (PyS) moieties in different molar ratios (21.4:1 ( P1 ), 3.9:1 ( P2 ), and 1.4:1 ( P3 )) were synthesized and employed as charge storage polymeric electret for nonvolatile organic field‐effect transistor (OFET) memory application. The impact of varying the molar ratio in side‐chain electron‐donating pyrene moieties on the thermal, optical, photophysical, electrochemical, and electrical properties of the resulting pendant copolymers was evaluated to establish structure–property relationship. The OFET memory with P3 electret layer exhibits a largest memory window of 41.8 V, long retention time of 10⁴ s with memory ratio of 10⁵, and stable reversibility of at least 100 cycles due to enhanced field‐induced holes trapping ability from higher PyS composition ratio. Therefore, polymer electret with pendant functional moieties shows potential for use as trapping layer in OFET memory devices. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 910–917     

Synthesis of Complex Druglike Molecules by the Use of Highly Functionalized Bench‐Stable Organozinc Reagents

The reactivity of a representative set of 17 organozinc pivalates with 18 polyfunctional druglike electrophiles (informers) in Negishi cross‐coupling reactions was evaluated by high‐throughput experimentation protocols. The high‐fidelity scaleup of successful reactions in parallel enabled the isolation of sufficient material for biological testing, thus demonstrating the high value of these new solid zinc reagents in a drug‐discovery setting and potentially for many other applications in chemistry. Principal component analysis (PCA) clearly defined the independent roles of the zincates and the informers toward druggable‐space coverage.     

An antibody reactive to the Gly63–Lys68 epitope of NT-proBNP exhibits O-glycosylation-independent binding

The N-terminal fragment of prohormone brain natriuretic peptide (NT-proBNP) is a commonly used biomarker for the diagnosis of congestive heart failure, although its biological function is not well known. NT-proBNP exhibits heavy O-linked glycosylation, and it is quite difficult to develop an antibody that exhibits glycosylation-independent binding. We developed an antibody that binds to the recombinant NT-proBNP protein and its deglycosylated form with similar affinities in an enzyme immunoassay. The epitope was defined as Gly₆₃–Lys₆₈ based on mimetic peptide screening, site-directed mutagenesis and a competition assay with a peptide mimotope. The nearest O-glycosylation residues are Thr₅₈ and Thr₇₁; therefore, four amino acid residues intervene between the epitope and those residues in both directions. In conclusion, we report that an antibody reactive to Gly₆₃–Lys₆₈ of NT-proBNP exhibits O-glycosylation-independent binding.