Combining the biased and unbiased sampling strategy into one convenient free energy calculation method

Constructing a free energy landscape for a large molecule is difficult. One has to use either a high temperature or a strong driving force to enhance the sampling on the free energy barriers. In this work, we propose a mixed method that combines these two kinds of acceleration strategies into one simulation. First, it applies an adaptive biasing potential to some replicas of the molecule. These replicas are particularly accelerated in a collective variable space. Second, it places some unbiased and exchangeable replicas at various temperature levels. These replicas generate unbiased sampling data in the canonical ensemble. To improve the sampling efficiency, biased replicas transfer their state variables to the unbiased replicas after equilibrium by Monte Carlo trial moves. In comparison to previous integrated methods, it is more convenient for users. It does not need an initial reference biasing potential to guide the sampling of the molecule. And it is also unnecessary to insert many replicas for the requirement of passing the free energy barriers. The free energy calculation is accomplished in a single stage. It samples the data as fast as a biased simulation and it processes the data as simple as an unbiased simulation. The method provides a minimalist approach to the construction of the free energy landscape. © 2019 Wiley Periodicals, Inc.     

1, 1'-双(二苯基膦基)二茂铁介导的芳烃碳氢键芳基化反应制备联芳基骨架

The broad existence of the biaryl linkage in bioactive organic molecules and functional materials makes it an attractive synthesis target via construction of aryl-aryl carbon bonds. Transition metal catalyzed cross-coupling reactions of two pre-functionalized aryl partners, e.g., Suzuki-Miyaura cross-coupling and Negishi cross-coupling reactions, are the main methods typically used for the construction of biaryl linkages. Since the end of the last century, transition metal catalyzed direct C―H arylation of unactivated arenes has emerged as a practical alternative to the well-established cross-coupling strategies. However, the use of transition metal catalysts and/or organometallic reagents would lead to problems, such as the disposal of waste from large-scale syntheses and the removal of heavy metal contaminants from pharmaceutical intermediates. In this regard, the base-promoted homolytic aromatic substitution (BHAS) reaction of aryl halides with unactivated arenes offers a simpler strategy for the synthesis of biaryl scaffolds, and avoids the use of transition metals. Although the BHAS reaction can proceed to a small extent without any additives, particularly at elevated temperatures, the addition of organic promoters would significantly accelerate the reaction rate and improve the overall efficiency of the process. Over the past ten years, a wide variety of N- and O-based organic promoters have been developed to promote the BHAS reaction in the presence of the tert-butoxide base. The mechanism of the BHAS reaction has been studied extensively, and is accepted as occurring via a radical chain process involving an aryl radical. However, the role and mode of initiation of most organic promoters studied remain controversial. The development of more and varied organic promoters will surely promote the mechanistic understanding and further development of the BHAS reaction. Herein, we report that 1, 1'-bis(diphenylphosphino)ferrocene (dppf, or DPPF) can act as a P-based promoter to facilitate the direct arylation of unactivated arenes with aryl iodides using potassium tert-butoxide as the base and electron donor. A broad range of aryl iodides and arenes reacted smoothly under the optimized reaction conditions, giving arylated products in good yields and with high regio-selectivity. Intramolecular C―H arylation also worked well following a sequence of single electron transfer (SET)/initiation, 5-exo-trig aryl radical addition, ring expansion, deprotonation, and re-aromatization/propagation. A mechanistic study indicated that the diphenylphosphino group of dppf played a vital role in the initiation step by enhancing the SET-inhibiting ability of the tert-butoxide anion. A primary kinetic isotope effect was observed in the parallel reactions between 4-methoxy-iodobenzene with benzene and deuterated benzene, implying that the deprotonation of the cyclohexadienyl radical intermediate by tert-butoxide was the rate-determining step in the radical chain pathway.     

Regioselective hydroamination of diphenylphosphorylallenes to synthesize β-aminophosphine oxides

The regioselective hydroamination of diphenylphosphorylallenes has been developed using secondary amines as the amination reagents. This reaction protocol could be realized under ligand and transition metal-free conditions at room temperature and is tolerated to a diverse range of diphenylphosphorylallenes and amine substrates, affording a series of β-aminophosphine oxides in good yields after the reduction of the enamine intermediates.     

Sulfonium,an Underestimated Moiety for Structural Modification,Alters the Antibacterial Profile of Vancomycin Against Multidrug‐Resistant Bacteria

In the antibiotics arsenal, vancomycin is a last resort for the treatment of intractable infections. However, this situation is under threat because of the increasing appearance of vancomycin‐resistant bacteria (VRB). Herein, we report a series of novel vancomycin derivatives carrying a sulfonium moiety. The sulfonium–vancomycin derivatives exhibited enhanced antibacterial activity against VRB both in vitro and in vivo. These derivatives also exhibited activity against some Gram‐negative bacteria. The sulfonium modification enhanced the interaction of vancomycin with the bacterial cell membrane and disrupts membrane integrity. Furthermore, the in vivo pharmacokinetic profile, stability, and toxicity of these derivatives demonstrated good druggability of the sulfonium–vancomycin analogues. This work provides a promising strategy for combating drug‐resistant bacterial infection, and advances the knowledge on sulfonium derivatives for structural optimization and drug development.     

Theory assisted design of N-doped tin oxides for enhanced electrochemical CO2 activation and reduction

Clearly understanding the structure-function relationship and rational design of efficient CO_2 electrocatalysts are still the challenges.This article describes the molecular origin of high selectivity of formic acid on N-doped SnO_2 nanoparticles,which obtained via thermal treatment of g-C_3N_4 and SnCl_2·2H_2O precursor.Combined with density functional theory(DFT)calculations,we discover that N-doping effectively introduces oxygen vacancies and increases the charge density of Sn sites,which plays a positive role in CO_2 activation.In addition,N-doping further regulates the adsorption energy of*OCHO,*COOH,*H and promotes HCOOH generation.Benefited from above modulation,the obtained N-doped SnO_2 catalysts with oxygen vacancies(Ov-N-SnO_2)exhibit faradaic efficiency of 93% for C_1 formation,88% for HCOOH production and well-suppression of H_2 evolution over a wide range of potentials.     

New insight into hydrogen bond-mediated electron transfer

<正>Electron transfer (ET) is one of the most fundamental processes in nature, biological systems, and optoelectronic devices. The in-depth ET investigations of synthetic materials are of great significance for the understanding of those occurring in natural systems. Mixed-valence (MV) compounds,consisting of two bridged redox motifs that are structurally identical but different in valence, provide an appealing     

Vacancy-assisted diffusion of alkoxy species on rutile TiO2(110)

Using scanning tunneling microscopy (STM) and density functional theory simulations, we have studied the diffusion of alkoxy species formed by the dissociation of alcohols on bridge-bonded oxygen (BBO) vacancies (BBO(V)'s) on TiO2(110). At elevated temperatures (>or=400 K) the sequential isothermal STM images show that mobile BBO(V)'s mediate the diffusion of alkoxy species by providing space for alkyl-group-bearing BBO atom to diffuse into. The experimental findings are further supported by simulations that find that BBO(V) diffusion is the rate limiting step in the overall diffusion mechanism.     

Caustics method in dynamic fracture problem of orthotropic materials

Caustics method is a powerful optical technique in fracture mechanics because of its high sensitivity to stress gradients. In this paper, it is applied to resolve dynamic fracture problems in orthotropic composites. Considering most orthotropic materials are opaque, reflective caustics method is derived here by combining the fundamental principle of caustics method with the mechanical properties of orthotropic materials. Meanwhile, corresponding experiments are carried out for typical glass fiber-reinforced composites, where mode I and mixed-mode fracture states are taken into account. By recording and analyzing shadow spot patterns during the crack propagation process carefully, crack onset time, dynamic fracture toughness and crack growth velocity of orthotropic composite are determined. These results will be useful to evaluate the dynamic fracture properties of composites and further to optimize their designs.     

Second-harmonic generation in the thermal/electrical poling (100−x)GeS2·x(0.5Ga2S3·0.5CdS) chalcogenide glasses

Utilizing Maker fringe (MF) method, second-harmonic generation (SHG) has been observed within the GeS₂-Ga₂S₃-CdS pseudo-ternary glasses through thermal/electrical poling technique. The SHG phenomenon was considered to be the result of breakage of the glassy macroscopic isotropy originated from the reorientations of dipoles during the thermal/electrical poling process. Under the same poling condition conducted with 5 kV and 280 °C for 30 min, the maximum value of second-order nonlinear susceptibility χ⁽²⁾ of the poled (100−x)GeS₂·x(0.5Ga₂S₃·0.5CdS) glasses was obtained to be ≈4.36 pm/V when the value of x is equal to 30. Nonlinear dependence of χ⁽²⁾ on compositions of these glasses can be well explained according to the theory related to the reorientation of dipoles.