Syntheses and molecular structures of new cali

An unusual disproportionation reaction of the molybdenum(IV) and tungsten(IV) chlorides [MCl4L2] (M=Mo, L=Et2S, Et2O; M=W; L= Et2S) in the presence of p-tBu-calix[4]arene (Cax(OH)4) and triethylamine leads to d0 complexes [(CaxO4)[CaxO2(OH)2]M] (1) and d3 compounds (HNEt3)2[(CaxO4)2M2] (2). Complexes la (M = Mo), 1b (M = W), and the HCl adduct of 2a (M = Mo) have been structurally characterized. Compound 1a represents one of the few examples of a well-characterized molybdenum(VI) hexa-alkoxide complex of the type [Mo(OR)6]. Isolation and structural characterization of the side product [(CaxO4W)[kappa2(O)-kappa1(O)-CaxO3(OH)](CaxO4WCl)] (3) suggests the intermediacy of chloro-containing calix[4]arene complexes in these reaction mixtures. The reaction of 1a with HCI provides [CaxO4MoCl2] (4a), the first well-defined example of a mixed molybdenum(VI) alkoxide halide compound of the general formula [MoClx(OR)6-x].     

冬凌草甲素分子印迹聚合物的制备及分子识别性能研究

以抗肿瘤药物分子冬凌草甲素为模板,甲基丙烯酸(MAA)为功能单体,乙二醇二甲基丙烯酸酯(ED-MA)作交联剂,采用沉淀聚合法和本体聚合法,制备对冬凌草甲素具有特定亲和选择性的分子印迹聚合物,并用激光粒度扫描和扫描电镜对聚合物的粒径和表面形貌进行了表征,采用平衡结合实验评价了两类分子印迹聚合物的吸附性能.结果表明,与使用...     

The role of molecular recognition in charge transport properties of doped polyaniline

Molecular recognition plays a significant role in the counterion-induced processibility, morphological features, and physical properties of doped polyaniline (PANI). The interaction of the counterion and solvent controls the chain conformation and, as a result, the formation of extended and localized electronic states; hence, it holds the key for tuning a wide range of electrical and optical properties of doped PANI. The combined effects of counterion, solvent, and processing conditions tune the metal-insulator transition, temperature dependence of conductivity, magnetoresistance, and so forth in doped PANI. The typical examples are shown in the case of PANI doped by camphor sulfonic acid, 2-acrylamido-2-methyl-1-propane sulfonic acid, and dodecylbenzoyl sulfonic acid.     

Chiral softballs: synthesis and molecular recognition properties.

Studies on the different congeners of the softball were undertaken to explore structural variants for enantioselective encapsulation. Two different spacer elements in the monomeric subunit render the dimeric softball chiral although the monomer itself is achiral. The dimers represent capsules with dissymmetric cavities with volumes ranging from 190 to 390 A(3). The cavities are distorted spheres, and asymmetric guests, such as naturally occurring terpenes, generally prefer one enantiomer of the capsule to its mirror image. The selectivities are moderate (up to 4:1). The complexation studies show that the host capsules are flexible enough to arrange themselves comfortably around a guest but still maintain enough rigidity to be influenced by the occupancy of a chiral guest. The enantiomeric capsules can interconvert (racemize) by dissociation and recombination of their subunits.     

氢醌卟啉的合成及其对醌的分子识别

利用氢醌与2-硝基卟啉直接反应，合成了2-(2’，5’—二羟基苯基)—5，10，15，20-四苯基卟啉，并利用紫外光谱、荧光光谱、电化学方法考察了它们对酯的分子识别，结果显示2—(2’，5’—二羟基苯基)-5，10，15，20-四苯基卟啉对醌具有较好的识别能力。     

Preparation of Z-L-Phe-OH-NBD imprinted microchannel and its molecular recognition study

An integrated microchip was presented for selective recognition of Z-L-Phe-OH-NBD, using molecular imprinting technique. Molecularly imprinted polymer (MIP) were prepared by copolymerization in the presence of template molecule Z-L-Phe-OH-NBD, in which methacrylic acid and 4-vinylpyridine were used as functional monomers and ethylene dimethacrylate used as crosslinker. Imprinted polymer particles were introduced into a microchannel fabricated with a new material i.e. poly(methylvinylsiloxane) by simply rapid prototyping method. Imprinted effects were evaluated by laser-induced fluorescence (LIF) detection where the results indicated that good selective recognition for Z-L-Phe-OH-NBD in the imprinted polymer was obtained; the adsorption percentage of Z-L-Phe-OH-NBD was 61%. In contrast to conventional molecular imprinting analysis, integration shortened overall analysis time from 4h to 10 min.     

Phosphorylated macrocycles: structures,complexing properties,and molecular recognition

Procedures were developed for functionalization of macrocycles by introducing a phosphonic group either directly linked to the aromatic rings (in the case of cyclophanes or calixarenes) or as a pendant arm. For these compounds to be used as artificial receptors for amino alcohols and amino acids, the host molecule must possess not only negative charges arising from the phosphonate moieties but also a hydrophobic binding site, such as electron-rich aromatic residues. We designed inter alia new dissymmetric macrocycles capable of being involved in three binding modes with guest molecules, viz., hydrogen bonding, electrostatic attraction, and π-cation interactions. The NMR characterization of the macrocycles, their stereochemistry in solution and in the solid state, and the use as chiral receptors for biologically relevant molecules are described. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1313–1330, June, 2005.     

Biomimetic copper(I)--CO complexes: a structural and dynamic study of a cali

Four novel calix[6]arene-based cuprous complexes are described. They present a biomimetic tris(imidazole) coordination core associated with a hydrophobic cavity that wraps the apical binding site. Each differs from the other by the methyl or ethyl substituents present on the phenoxyl groups (OR1) and on the imidazole arms (NR2) of the calix[6]arene structure. In solution, stable CO complexes were obtained. We have investigated their geometrical and dynamic properties with respect to the steric demand. IR and NMR studies revealed that, in solution, these complexes adopted two distinct conformations. The preferred conformation was dictated only by the size of the OR1 group. When R1 was an ethyl group, the complex preferentially adopted a flattened C3-symmetrical structure. The corresponding helical enantiomers were in conformational equilibrium, which, however, was slow on the 1H NMR time scale at -80 degrees C. When R1 was a methyl group, the low-temperature NMR spectra revealed the partial inclusion of one tBu group. The complex wobbled between three dissymmetric but equivalent conformations. Hence, small differences in the steric demand of the calixarene's skeleton changed the geometry and dynamics of the system. Indeed, this supramolecular control was promoted by the strong conformational coupling between the metal center and the host structure. Interestingly, this was not only the result of a covalent preorganization, but also stemmed from weak interactions within the hydrophobic pocket. The vibrational spectra of the bound CO were revealed to be a sensitive gauge of this supramolecular behavior, similar to copper proteins in which allosteric effects are common.     

Pattern recognition display methods for the analysis of computed molecular properties

Summary Pattern recognition methods, particularly the unsupervised learning techniques, are well suited for the preliminary analysis of the large data sets produced by computer chemistry. The use of linear and non-linear display methods for such exploratory analysis are exemplified with the aid of two data sets of biologically active molecules. Advantages and disadvantages of these techniques are discussed.     

核苷磷酸盐对含双芘侧链荧光敏感器化合物的荧光猝灭与分子识别

合成了一种在水溶液中对核苷磷酸盐ATP,ADP,AMP阴离子具有识别能力的荧光化学敏感器分子---化合物1。通过检测化合物1在水溶液中芘激基缔合物荧光发射强度随核苷磷酸盐、腺嘌呤等的加入而引起的变化,求出不同核苷磷酸盐及腺嘌呤对芘激基缔合物荧光发射的猝灭常数,并进行了比较研究。利用荧光发射强度随不同核苷磷酸盐引入而发生的变化计算出化合物1对不同核苷磷酸盐进行配位的配位稳定常数。结果表明所合成的化合物1对ATP有着良好的识别力选择功能。此外,还利用分子力学的计算方法对化合物1及其与核苷磷酸盐形成配合物后的分子构象及几何尺寸作了计算,并结合实验结果进行了初步讨论。     

Cooperativity in drug-DNA recognition: a molecular dynamics study.

NMR studies have shown that the minor groove-binding ligand Hoechst 33258 binds to the two T4/A4 tracts within the duplex d(CTTTTCGAAAAG)2 in a highly cooperative manner, such that in titration experiments no intermediate 1:1 complex can be detected. The NMR-derived structures of the free DNA and the 2:1 complex have been obtained, but can shed little light on what the origins of this cooperativity may be. Here we present the results of a series of molecular dynamics simulations on the free DNA, the 1:1 complex, and the 2:1 complex, which have been designed to enable us to calculate thermodynamic parameters associated with the molecular recognition events. The results of the molecular dynamics studies confirm that structural factors alone cannot explain the cooperativity observed, indeed when enthalpic and hydration factors are looked at in isolation, the recognition process is predicted to be slightly anticooperative. However, when changes in configurational entropy are taken into account as well, the overall free energy differences are such that the calculated cooperativity is in good agreement with that observed experimentally. The results indicate the power of molecular dynamics methods to provide reasonable explanations for phenomena that are difficult to explain on the basis of static models alone, and provide a nice example of the concept of "allostery without conformational change".     

Substrate recognition by norovirus polymerase: microsecond molecular dynamics study

Molecular dynamics simulations of complexes between Norwalk virus RNA dependent RNA polymerase and its natural CTP and 2dCTP (both containing the O5′–C5′–C4′–O4′ sequence of atoms bridging the triphosphate and sugar moiety) or modified coCTP (C5′–O5′–C4′–O4′), cocCTP (C5′–O5′–C4′–C4′′) substrates were produced by means of CUDA programmable graphical processing units and the ACEMD software package. It enabled us to gain microsecond MD trajectories clearly showing that similar nucleoside triphosphates can bind surprisingly differently into the active site of the Norwalk virus RNA dependent RNA polymerase. It corresponds to their different modes of action (CTP—substrate, 2dCTP—poor substrate, coCTP—chain terminator, cocCTP—inhibitor). Moreover, extremely rare events—as repetitive pervasion of Arg182 into a potentially reaction promoting arrangement—were captured.     

Monolithic molecularly imprinted polymer for sulfamethoxazole and molecular recognition properties in aqueous mobile phase

A monolithic molecularly imprinted polymer (monolithic MIP) for sulfamethoxazole (SMO) was prepared by in situ polymerization method as the HPLC stationary phase. By optimizing the polymerization conditions, the monolithic MIP showed highly specific recognition for the template SMO over its three structurally related analogs. As shown by SEM and the pore size distribution profile, the resultant MIP monolith showed a main pore diameter of 594 nm and a large specific surface area of 124 m² g⁻¹, this allowed the mobile phase to flow through the column with low backpressure. Furthermore, the recognition abilities of the monolithic MIP in aqueous and organic media were studied. The results exhibited that the monolithic MIP possessed excellent recognition ability in aqueous media. Hydrophobic interactions, in addition to shape recognition, were the dominant effect for recognition in the mobile phase with high water content. Moreover, the binding sites and the dissociation constant were also determined by frontal chromatography as 122 μmol g⁻¹ and 1.88 × 10⁻⁵ mol L⁻¹, respectively, which demonstrated that the obtained SMO-MIP monolith had a high binding capacity and strong affinity ability to the template molecule. Furthermore, the resultant SMO-MIP monolith was used as HPLC column directly to determine the SMO contents in three kinds of pharmaceutical tablets with the optimized aqueous mobile phase.     

Complexity in molecular recognition

The anomer selectivity of artificial carbohydrate receptors was studied using in silico methods in order to shed light on the thermodynamic driving forces at work during molecular recognition in general. The contributions of relevant intermolecular hydrogen bonds were investigated by means of generalized compliance constants in order to dissect important from less important non-covalent interactions. Even at this moderately low rung on the ladder of complexity essential aspects of molecular recognition are not explainable in terms of additive intermolecular interactions. Though molecular recognition seems to be a complex and emergent property, a rationale for the diastereoselectivity of carbohydrate receptors was obtained by a combination of experimental data, free energy simulations and ab initio calculations.     

对羟基苯甲酸、水杨酸分子印迹聚合物分子识别性质的 研究

以对羟基苯甲酸(4-HBA)为模板分子,4-乙烯吡啶(4-Vpy)为功能单体,制备得到了4-HBA分子印迹聚合物P(4-HBA),研究了该聚合物的分子识别机理,并与在同样条件下制备的水杨酸(SA)分子印迹聚合物P(SA)进行了分子识别能力的比较。结果表明：P(SA)比P(4-HBA)具有更好的分子识别能力。这是由于SA的酸性较4-HBA强,因此与碱性功能单体4-Vpy之间的静电作用更强,从而得到的复合物更稳定。本实验结果证明：功能单体与模板分子形成稳定的复合物是得到分子识别能力高的模板聚合物的前提条件。本文将有助于对分子印迹的过程以及分子印迹聚合物分子识别机理的进一步理解,并且对于根据模板分子的性质预测MIP的分子识别能力也将具有一定的指导意义。     

The influence of constitutional isomerism and change on molecular recognition processes

Three constitutionally isomeric bis(naphthylmethyl)ammonium ions, in which the two naphthyl groups are substituted 1) both at their 1-positions, 2) one at its 1-position and the other at its 2-position, and 3) both at their 2-positions, have been investigated separately in solution for their propensities to undergo spontaneous self-assembly with three different [24]crown-8 derivatives, namely, pyrido[24]crown-8 (P24C8), dipyrido[24]crown-8 (DP24C8) and dibenzo[24]crown-8 (DB24C8), in turn to form [2]pseudorotaxanes. The strengths of the 1:1 complexes depend on the composition of the secondary dialkylammonium ions and on the nature of the crown ether hosts; generally, as far as the guest cation is concerned, the 1/1- and 2/2-isomers form stronger complexes, as indicated by stability constant measurements, than the 1/2-isomer and, as far as the crown ethers are concerned, the more flexible P24C8 is a much more efficient host than either DP24C8 or DB24C8. The rates of formation of the [2]pseudorotaxanes are fast (i.e., taking no more than a few minutes) in solution with the exception of one case, that is, in which the crown ether host is DB24C8 and the guest cation is the 1/1-isomer, when it can take upwards of one month for the complexation-decomplexation equilibrium to be established at room temperature. In all cases, the equilibrium between complexed and uncomplexed species is slow on the NMR timescale, allowing the determination of stability constants to be made readily using the single-point method. X-ray crystallography and molecular modeling have been used to gain insight into ground and transition state interactions, respectively, in some of the [2]pseudorotaxanes. The relative stabilities of the three [2]pseudorotaxanes formed by each guest cation in the presence of the three crown ether hosts were also evaluated in solution by competition experiments that were monitored by (1)H NMR spectroscopy. By and large the results of the competition experiments could be predicted on the basis of the derived stability constants for the individual [2]pseudorotaxanes.     

Chemical modifications of AFM tips for the study of molecular recognition events

The use of AFM to study molecular recognition events at an incredible level of sensitivity is currently a very active field of research. In order to get information at the single molecule level, it is mandatory to modify in a precise manner the AFM tip to anchor either ligand or receptor molecules. In the following lines, we review the achievements in tip modifications and illustrate the scope and limitations of the different strategies that have been reported.