Density functional theory study of indirect nuclear spin-spin coupling constants with spin-orbit corrections

This work outlines the calculation of indirect nuclear spin-spin coupling constants with spin-orbit corrections using density functional response theory. The nonrelativistic indirect nuclear spin-spin couplings are evaluated using the linear response method, whereas the relativistic spin-orbit corrections are computed using quadratic response theory. The formalism is applied to the homologous systems H2X (X=O,S,Se,Te) and XH4 (X=C,Si,Ge,Sn,Pb) to calculate the indirect nuclear spin-spin coupling constants between the protons. The results confirm that spin-orbit corrections are important for compounds of the H2X series, for which the electronic structure allows for an efficient coupling between the nuclei mediated by the spin-orbit interaction, whereas in the case of the XH4 series the opposite situation is encountered and the spin-orbit corrections are negligible for all compounds of this series. In addition we analyze the performance of the density functional theory in the calculations of nonrelativistic indirect nuclear spin-spin coupling constants.     

Koszul–Sullivan Models and the Cohomology of Certain Solvmanifolds

In this paper we develop a technique of working with graded differential algebra models of solvmanifolds, overcoming the main difficulty arising from the non-nilpotency of the corresponding Mostow fibrations. A graded differential model for solvmanifolds of the form G/ with G=RN is presented (N is a nilpotent Lie group, G is a semi-direct product). As an application, we prove the Benson–Gordon conjecture in dimension four.     

Fixed points and powers of self-maps of -spaces

We give a new proof of the following result due to Duan: Let be any self-map of a finite connected -space. Then has a fixed point if . Our proof is based on an approach due to Steve Halperin, whereby the Lefschetz number of a self-map is expressed in terms of the eigenvalues of the induced homomorphism of rational homotopy groups. This allows us to give a considerably shorter proof which avoids most of the technicalities of the original proof.

     

Current trends in lead discovery: Are we looking for the appropriate properties?

The new drug discovery paradigm is based on high-throughputtechnologies, both with respect to synthesis and screening. Theprogression HTS hits lead series candidatedrug marketed drugappears to indicate that the probability of reaching launched status isone in a million. This has shifted the focus from good qualitycandidate drugs to good quality leads. We examined the current trendsin lead discovery by comparing MW (molecular weight), LogP(octanol/water partition coefficient, estimated by Kowwin [17])and LogSw (intrinsic water solubility, estimated by Wskowwin [18])for the following categories: 62 leads and 75 drugs [11];compounds in the development phase (I, II, III and launched), asindexed in MDDR; and compounds indexed in medicinal chemistry journals[ref. 20], categorized according to their biological activity.Comparing the distribution of the above properties, the 62 leadstructures show the lowest median with respect to MW (smaller) and LogP(less hydrophobic), and the highest median with respect to LogSw (moresoluble). By contrast, over 50% of the medicinal chemistry compoundswith activities above 1 nanomolar have MW > 425, LogP > 4.25 andLogSw < -4.75, indicating that the reported active compounds arelarger, more hydrophobic and less soluble when compared to time-testedquality leads. In the MDDR set, a progressive constraint to reduce MWand LogP, and to increase LogSw, can be observed when examining trendsin the developmental sequence: phase I, II, III and launched drugs.These trends indicate that other properties besides binding affinity,e.g., solubility and hydrophobicity, need to be considered whenchoosing the appropriate leads.     

Eugenol-Functionalized Magnetite Nanoparticles Modulate Virulence and Persistence in Pseudomonas aeruginosa Clinical Strains

Efficient antibiotics to cure Pseudomonas aeruginosa persistent infections are currently insufficient and alternative options are needed. A promising lead is to design therapeutics able to modulate key phenotypes in microbial virulence and thus control the progression of the infectious process without selecting resistant mutants. In this study, we developed a nanostructured system based on Fe₃O₄ nanoparticles (NPs) and eugenol, a natural plant-compound which has been previously shown to interfere with microbial virulence when utilized in subinhibitory concentrations. The obtained functional NPs are crystalline, with a spherical shape and 10–15 nm in size. The subinhibitory concentrations (MIC 1/2) of the eugenol embedded magnetite NPs (Fe₃O₄@EUG) modulate key virulence phenotypes, such as attachment, biofilm formation, persister selection by ciprofloxacin, and the production of soluble enzymes. To our knowledge, this is the first report on the ability of functional magnetite NPs to modulate P. aeruginosa virulence and phenotypic resistance; our data highlights the potential of these bioactive nanostructures to be used as anti-pathogenic agents.     

The antioxidant response induced by Lonicera caerulaea berry extracts in animals bearing experimental solid tumors

Lonicera caerulea is a species of bush native to the Kamchatka Peninsula (Russian Far East) whose berries have been extensively studied due to their potential high antioxidant activity. The aim of our work was to investigate the in vivo effects of the antioxidant action of Lonicera caerulea berry extracts on the dynamics of experimentally-induced tumors. Our data showed that aqueous Lonicera caerulaea extracts reduced the tumor volume when administered continuously during the tumor growth and development stages, but augmented the tumor growth when the administration of extracts started three weeks before tumor grafting. Prolonged administration of Lonicera caerulaea berry extracts induced the antioxidant defense mechanism in the tumor tissues, while surprisingly amplifying the peripheral oxidative stress.     

Longitudinal dynamics of trains—a non-smooth approach

An efficient and straightforward algorithm for the integration of the constrained systems is developed in the present work. Some of the fundamental issues of contact dynamics are briefly reviewed. Considering Gauss?? least constraint principle, an intuitive and effective computation method of the constraint forces is arrived at. The contact problem is solved by means of the generalized matrix inverse (GI) embedded in an appropriate algorithm and the numerical integration is event-driven. The method is applied to the study of train longitudinal dynamics which is essential for comfort and running safety. Due to the complexity of the phenomena and the presence of dry friction, the investigations have been carried out by numerical methods using regularization. Based on the non-smooth dynamics approach, in the present paper, a comprehensive model is presented. Set-value friction of Coulomb??s law type is accounted for and motion equations are formulated as a differential inclusion. Application examples are presented. Simulations demonstrate the existence of specific phenomena like stick?Cslip and offset in the final equilibrium position. Computational efficiency is dramatically improved compared with previous models, while computation speed is increased by at least an order of magnitude. A wide class of problems may be solved using the present method, as is pointed out in the article.     

含2-N,N-二甲氨基嘧啶环与噻吩环结构的共轭聚合物的合成及其性能

合成了一种新型单体2-N,N-二甲氨基-4,6-二氯嘧啶(ADNP).以二氯-1,3-双(二苯基磷)丙烷基镍(Ⅱ)作催化剂,通过2,5-二溴噻吩格氏试剂与该单体共聚得到了一种新型共轭聚合物,聚[(2-N,N-二甲胺基嘧啶-4,6-二)-2,5-噻吩](PThPm).采用FT-IR、1H-NMR等测试手段对新型单体与共聚物的结构进行了表征,并用UV-Vis、荧光光谱、X射线衍射、循环伏安、热重分析(TGA)等测试方法对单体和共聚物进行了性能分析.结果表明:共聚物在420 nm处出现UV-Vis吸收峰,在528 nm处出现荧光发射峰;共聚物的DMF溶液存在酸致变色现象,加入CF3COOH和CH3SO3H后,溶液由淡绿黄色转变为淡红色,UV-Vis吸收峰发生红移;PThPm共聚物有一定的结晶性和热稳定性;在-1.8～ 1.8 V之间出现电致变色现象,电极周围的溶液颜色从深蓝色变成深红色.