New cyanine-oligonucleotide conjugates: relationships between chemical structures and properties

Because the influence of the chemical structure of monomethine cyanine-oligo-2'-deoxyribonucleotide (ODN) conjugates on their binding and fluorescence properties has remained largely undetermined, we synthesized and studied a wide range of conjugates with various structural patterns. Different cyanine dyes such as thiocyanine, quinocyanine, and thiazole orange isomers were obtained. In the case of unsymmetrical cyanines, the linker was attached to either the quinoline or the benzothiazole nucleus. The influence of the ODN counterpart was evaluated by linking the cyanines to the 5'-end or to an internucleotidic phosphate. In the first case, the influence of neighboring nucleic bases was studied, whereas in the second, the stereochemical configuration at the phosphorus atom bearing the cyanine was investigated. We report here on relationships between the structures of the dyes and conjugates and some of their properties, such as the stability and fluorescence changes observed on their hybridization with the target sequence. This study provides useful information towards the design of ODN-cyanine conjugates.     

Bioelectrodes for evaluating molecular therapeutic and toxicity properties

Recent progress on material designs merged with nanotechnology and biotechnology strategies has advanced studies of complex biological samples on electrodes for cytochrome P450 (CYP)–driven biocatalytic reactions (e.g. liver membrane fractions, cells, and various organ-specific CYP extracts). In addition, protein engineering of CYP enzymes with their reductase partner in membranes (e.g. baculovirus- or Escherichia coli bacteria–expressed CYP microsomes) and other recombinant strategies (e.g. engineered CYP and reductase fusion domains and site-directed CYP mutagenesis) are promising sustainable approaches for offering abundant sources of CYP enzymes for electrocatalytic applications. The combination of in silico and experimental electroanalytical methods with hyphenated approaches and biological assays can offer early and rigorous profiling of new drugs and specialty chemicals for safe exposure and beneficial use.     

Interaction between secondary and higher schools: A basis for fundamental chemical education

Nowadays, within the Russian system of higher education there are two subsystems working fairly independently. One is mass higher education, and other is fundamental (quality) education. The educational reform which has been underway since the mid-1990s only makes worse the situation. Every year higher school teachers note a decrease of the quality of applicants and first-year students, gaps in their knowledge of chemistry, mathematics, and other disciplines. Under such conditions, universities should provide themselves with a corpse of the adequately prepared applicants. What can be done in order to preserve traditions of the Russian fundamental university education? First of all, quality textbooks for school pupils and applicants can be written and published. Further, connections between higher education institutions and secondary school in various regions of the country can be established and developed. Another very important task consists in organizing and conducting science Olympiads for schoolchildren and applicants. All these activities are being undertaken now by the Moscow State University.     

Toward rational and modular molecular design in soft matter engineering

This essay discusses some preliminary thoughts on the development of a rational and modular approach for molecular design in soft matter engineering and proposes ideas of structural and functional synthons for advanced functional materials. It echoes the Materials Genome Initiative by practicing a tentative retro-functional analysis(RFA) scheme. The importance of hierarchical structures in transferring and amplifying molecular functions into macroscopic properties is recognized and emphasized. According to the role of molecular segments in final materials, there are two types of building blocks: structural synthon and functional synthon. Guided by a specific structure for a desired function, these synthons can be modularly combined in various ways to construct molecular scaffolds. Detailed molecular structures are then deduced, designed and synthesized precisely and modularly. While the assembled structure and property may deviate from the original design, the study may allow further refinement of the molecular design toward the target function. The strategy has been used in the development of soft fullerene materials and other giant molecules. There are a few aspects that are not yet well addressed:(1) function and structure are not fully decoupled and(2) the assembled hierarchical structures are sensitive to secondary interactions and molecular geometries across different length scales. Nevertheless, the RFA approach provides a starting point and an alternative thinking pathway by provoking creativity with considerations from both chemistry and physics. This is particularly useful for engineering soft matters with supramolecular lattice formation, as in giant molecules, where the synthons are relatively independent of each other.     

Ring system-based chemical graph generation for de novo molecular design

Generating chemical graphs in silico by combining building blocks is important and fundamental in virtual combinatorial chemistry. A premise in this area is that generated structures should be irredundant as well as exhaustive. In this study, we develop structure generation algorithms regarding combining ring systems as well as atom fragments. The proposed algorithms consist of three parts. First, chemical structures are generated through a canonical construction path. During structure generation, ring systems can be treated as reduced graphs having fewer vertices than those in the original ones. Second, diversified structures are generated by a simple rule-based generation algorithm. Third, the number of structures to be generated can be estimated with adequate accuracy without actual exhaustive generation. The proposed algorithms were implemented in structure generator Molgilla. As a practical application, Molgilla generated chemical structures mimicking rosiglitazone in terms of a two dimensional pharmacophore pattern. The strength of the algorithms lies in simplicity and flexibility. Therefore, they may be applied to various computer programs regarding structure generation by combining building blocks.     

环氧酮肽蛋白酶体抑制剂的构效关系及基于分子相似性的分子设计

针对56个环氧酮肽衍生物,分别采用比较分子场分析(comparative molecular field analysis,CoMFA)、比较分子相似性形状指数分析(comparative molecular similarity indices analysis,CoMSIA)、Topomer CoMFA、Holo-gram QSAR(HQSAR)以及基于一维和二维描述符的支持向量机(support vector machine,SVM)方法进行了细致的构效关系研究。研究显示:通过引入一维和二维描述符的SVM建模方法,避免了柔性分子在三维构效关系研究中的构象选择和叠合难题,亦可有效避免过拟合现象的发生。所建最优SVM模型的决定系数R2、均方根误差(RMS)、交互验证系数Q2和外部预测R2pred分别为0.681,0.436,0.572和0.641。分析结果显示:电性、拓扑特征、疏水性和分子体积是影响环氧酮肽蛋白酶体抑制活性的主要因素。在此基础上,以活性最高样本分子(CID:42638286的)为模板,基于相似性评价方法对其侧链进行设计,结合Lipinski"5规则"类药性筛选,共得到12个新颖目标分子,且预测活性均达到纳摩尔水平。     

Stilbene‐containing polyactylenes: Molecular design,synthesis, and relationship between molecular structure and NLO properties

Polyacetylenes ( P1–P4 ) containing different stilbene groups, ? [(CH?C) ? Ph? CH?CH? Ph? R]_n? (R?OC_mH_2m+1 (m = 4 ( P1 ), 10 ( P2 ), 16 ( P3 )), or NO₂ ( P4 )) were designed and synthesized, respectively, using [Rh(nbd)Cl]₂ as a catalyst. Their structures and properties were characterized and evaluated by FTIR, ¹H‐NMR, ¹³C‐NMR, GPC, and UV, PL, respectively. The optical limiting and nonlinear optical properties were investigated by using a frequency doubled, Q‐switched, mode‐locked Continuum ns/ps Nd:YAG laser system and their optical limiting mechanism was discussed. It is surprising to see that the stilbene pendants endow the polyacetylenes with a high thermal stability (T_d ≥ 270 °C), novel optical limiting properties and large third‐order nonlinear optical susceptibilities (up to 4.61 × 10^?10 esu). The optical limiting mechanism is mainly originated from reverse saturable absorption of molecules. In addition, it is found that the polymer with electron accepted NO₂ moiety exhibits better optical properties than that with electron donated alkoxy group because of larger π electron delocalization and dipolar effect. The strong interaction between stilbene pendants and the polyene main chain significantly results in red‐shift of fluorescence emitting peak. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 4529–4541, 2008     

Salts of extended tetrathiafulvalene analogues: relationships between molecular structure, electrochemical properties and solid state organisation

By considering the structures of many salts derived from extended TTF analogues, relationships between the molecular architecture of the donors with their electrochemical properties and their stacking mode in the salts are presented in this critical review. Three categories of donors corresponding to their extension modes have been considered. Firstly, for linearly extended TTFs the crucial role of the spacer in modifying the electrochemical properties and the packing mode in the salts is presented. Secondly, bidimentional extension of the donors obtained by linking several dithiafulvenyl units on a TTF core led to materials with increased dimensionality. Finally, the last class corresponds to the fusion, directly or across a benzene ring, of TTF frameworks. The former are the base of many salts with metallic behaviour. (148 references.).     

Exploiting clock transitions for the chemical design of resilient molecular spin qubits

Molecular spin qubits are chemical nanoobjects with promising applications that are so far hampered by the rapid loss of quantum information, a process known as decoherence. A strategy to improve this situation involves employing so-called Clock Transitions (CTs), which arise at anticrossings between spin energy levels. At CTs, the spin states are protected from magnetic noise and present an enhanced quantum coherence. Unfortunately, these optimal points are intrinsically hard to control since their transition energy cannot be tuned by an external magnetic field; moreover, their resilience towards geometric distortions has not yet been analyzed. Here we employ a python-based computational tool for the systematic theoretical analysis and chemical optimization of CTs. We compare three relevant case studies with increasingly complex ground states. First, we start with vanadium(iv)-based spin qubits, where the avoided crossings are controlled by hyperfine interaction and find that these S = 1/2 systems are very promising, in particular in the case of vanadyl complexes in an L-band pulsed EPR setup. Second, we proceed with a study of the effect of symmetry distortions in a holmium polyoxotungstate of formula [Ho(W₅O₁₈)₂]⁹⁻ where CTs had already been experimentally demonstrated. Here we determine the relative importance of the different structural distortions that causes the anticrossings. Third, we study the most complicated case, a polyoxopalladate cube [HoPd₁₂(AsPh)₈O₃₂]⁵⁻ which presents an unusually rich ground spin multiplet. This system allows us to find uniquely favorable CTs that could nevertheless be accessible with standard pulsed EPR equipment (X-band or Q-band) after a suitable chemical distortion to break the perfect cubic symmetry. Since anticrossings and CTs constitute a rich source of physical phenomena in very different kinds of quantum systems, the generalization of this study is expected to have impact not only in molecular spin science but also in other related fields such as molecular photophysics and photochemistry.

We employ a python computational tool to compare 3 relevant case studies with increasingly complex ground states: vanadyl complexes, Ho(iii) square antiprisms and Ho(iii) cubic structures.     

Transferrable property relationships between magnetic exchange coupling and molecular conductance

Calculated conductance through Au_n–S–Bridge–S–Au_n (Bridge = organic σ/π-system) constructs are compared to experimentally-determined magnetic exchange coupling parameters in a series of Tp^Cum,MeZnSQ–Bridge–NN complexes, where Tp^Cum,Me = hydro-tris(3-cumenyl-1-methylpyrazolyl)borate ancillary ligand, Zn = diamagnetic zinc(ii), SQ = semiquinone (S = 1/2), and NN = nitronylnitroxide radical (S = 1/2). We find that there is a nonlinear functional relationship between the biradical magnetic exchange coupling, J_D→A, and the computed conductance, g_mb. Although different bridge types (monomer vs. dimer) do not lie on the same J_D→Avs. g_mb, curve, there is a scale invariance between the monomeric and dimeric bridges which shows that the two data sets are related by a proportionate scaling of J_D→A. For exchange and conductance mediated by a given bridge fragment, we find that the ratio of distance dependent decay constants for conductance (β_g) and magnetic exchange coupling (β_J) does not equal unity, indicating that inherent differences in the tunneling energy gaps, Δε, and the bridge–bridge electronic coupling, H_BB, are not directly transferrable properties as they relate to exchange and conductance. The results of these observations are described in valence bond terms, with resonance structure contributions to the ground state bridge wavefunction being different for SQ–Bridge–NN and Au_n–S–Bridge–S–Au_n systems.

Calculated conductance through Au_n–S–Bridge–S–Au_n constructs are compared to experimental magnetic exchange coupling parameters in Tp^Cum,MeZn(SQ–Bridge–NN) complexes, where SQ = semiquinone radical and NN = nitronylnitroxide radical.     

Simulation of chemical metabolism for fate and hazard assessment. V. Mammalian hazard assessment

Animals and humans are exposed to a wide array of xenobiotics and have developed complex enzymatic mechanisms to detoxify these chemicals. Detoxification pathways involve a number of biotransformations, such as oxidation, reduction, hydrolysis and conjugation reactions. The intermediate substances created during the detoxification process can be extremely toxic compared with the original toxins, hence metabolism should be accounted for when hazard effects of chemicals are assessed. Alternatively, metabolic transformations could detoxify chemicals that are toxic as parents. The aim of the present paper is to describe specificity of eukaryotic metabolism and its simulation and incorporation in models for predicting skin sensitization, mutagenicity, chromosomal aberration, micronuclei formation and estrogen receptor binding affinity implemented in the TIMES software platform. The current progress in model refinement, data used to parameterize models, logic of simulating metabolism, applicability domain and interpretation of predictions are discussed. Examples illustrating the model predictions are also provided.     

Simulation of chemical metabolism for fate and hazard assessment. V. Mammalian hazard assessment

Animals and humans are exposed to a wide array of xenobiotics and have developed complex enzymatic mechanisms to detoxify these chemicals. Detoxification pathways involve a number of biotransformations, such as oxidation, reduction, hydrolysis and conjugation reactions. The intermediate substances created during the detoxification process can be extremely toxic compared with the original toxins, hence metabolism should be accounted for when hazard effects of chemicals are assessed. Alternatively, metabolic transformations could detoxify chemicals that are toxic as parents. The aim of the present paper is to describe specificity of eukaryotic metabolism and its simulation and incorporation in models for predicting skin sensitization, mutagenicity, chromosomal aberration, micronuclei formation and estrogen receptor binding affinity implemented in the TIMES software platform. The current progress in model refinement, data used to parameterize models, logic of simulating metabolism, applicability domain and interpretation of predictions are discussed. Examples illustrating the model predictions are also provided.     

A fundamental connection between symmetry and spatial localization properties of basis sets

The problem of the compatibility between symmetry and localization properties of basis sets is addressed here. It is shown that both concepts are closely related from a fundamental point of view through the notion of invariance extent. This quantity is a functional that depends on the symmetry group and the basis set choices, and it is shown that all basis sets adapted in a general way to symmetry, i.e. induced from irreducible bases of the subgroups, are stationary points of it. In particular, the usual irreducible bases of the full group display a maximal invariance extent, while those symmetry-adapted basis sets that display a minimal value of this quantity feature in most cases the same symmetry properties as localized functions obtained by means of the Boys scheme. The most relevant conclusions are illustrated by means of simple molecular and periodic examples.