Cooperativity between metal ions in the cleavage of phosphate diesters and RNA by dinuclear Zn(II) catalysts

A series of ligands containing linked 1,4,7-triazacyclononane macrocycles are studied for the preparation of dinuclear Zn(II) complexes including 1,3-bis(1,4,7-triazacyclonon-1-yl)-2-hydroxypropane (L2OH), 1,5-bis(1,4,7-triazacyclonon-1-yl)pentane (L3), 2,9-bis(1-methyl-1,4,7-triazacyclonon-1-yl)-1,10-phenanthroline (L4), and alpha,alpha'-bis(1,4,7-triazacyclonon-1-yl)-m-xylene (L5). The titration of these ligands with Zn(NO(3))(2) was monitored by (1)H NMR. Each ligand was found to bind two Zn(II) ions with a very high affinity at near neutral pH under conditions of millimolar ligand and 2 equiv of Zn(NO(3))(2). In contrast, a stable mononuclear complex was formed in solutions containing 5.0 mM L2OH and 1 equiv of Zn(NO(3))(2). (1)H and (13)C NMR spectral data are consistent with formation of a highly symmetric mononuclear complex Zn(L2OH) in which a Zn(II) ion is sandwiched between two triazacyclononane units. The second-order rate constant k(Zn) for the cleavage of 2-hydroxypropyl-4-nitrophenyl phosphate (HPNP) at pH 7.6 and 25 degrees C catalyzed by Zn(2)(L2O) is 120-fold larger than that for the reaction catalyzed by the closely related mononuclear complex Zn(L1) (L1 = 1,4,7-triazacyclononane). By comparison, the observation that the values of k(Zn) determined under similar reaction conditions for cleavage of HPNP catalyzed by the other Zn(II) dinuclear complexes are only 3-5-fold larger than values of k(Zn) for catalysis by Zn(L1) provides strong evidence that the two Zn(II) cations in Zn(2)(L2O) act cooperatively in the stabilization of the transition state for cleavage of HPNP. The extent of cleavage of an oligoribonucleotide by Zn(L1), Zn(2)(L5), and Zn(2)(L2O) at pH 7.5 and 37 degrees C after 24 h incubation is 4,10, and 90%. The rationale for the observed differences in catalytic activity of these dinuclear Zn(II) complexes is discussed in terms of the mechanism of RNA cleavage and the structure and speciation of these complexes in solution.     

The mechanism of cleavage and isomerisation of RNA promoted by an efficient dinuclear Zn2+ complex

The cleavage and isomerisation of uridine 3'-alkylphosphates was studied in the presence of a dinuclear Zn(2+) complex, 3. The rate acceleration of the cleavage by 1 mM 3 is approximately 10(6)-fold under neutral conditions. Most remarkably, the complex also promotes the isomerisation of phosphodiester bonds, although the rate-enhancement is more modest: under neutral conditions complex 3 (1 mM) catalyses isomerisation by about 500-fold. The observation of this reaction shows that the reactions of these substrates catalysed by 3 proceed through a stepwise mechanism involving an intermediate phosphorane. A β(lg) value of -0.92 was determined for the 3-promoted cleavage reaction, and modest kinetic solvent deuterium isotope effects ranging from 1.5 to 2.8 were observed. Isomerisation was less sensitive to the nature of the esterifying group, with a β value of -0.5, and the kinetic solvent deuterium isotope effects were less than 1.5. Most of these characteristics of the 3-promoted cleavage are very similar to those for the cleavage of nucleoside 3'-phosphotriesters. These data are explained by a mechanism in which the complex primarily acts as an electrophilic catalyst neutralising the charge on the phosphate and stabilising an intermediate phosphorane, with general acid catalysis promoting the cleavage reaction. In contrast to the behaviour of triesters, isomerisation is significantly slower than cleavage; this suggests that the changes in geometry that occur during isomerisation lead to a much less stable complex between 3 and the phosphorane intermediate.     

新型金属胶束模拟酶对羧酸酯与磷酸酯的催化水解

报道了三种新的含醇羟基、胺基或咪唑基长链配体与铜锌离子构成的金属胶束对几种羧酸酯与磷酸酯底物催化水解动力学。结果表明,设计的金属胶束N-十四烷基-2-(N-2'-羟乙基氨基甲基)咪唑锌铜(2a,2b)在共胶束CTAB(溴化十六烷基三甲铵)存在下,对强配位羧酸酯对硝基苯酚-2-吡啶甲酸酯具有很强的催化水解能力,对磷酸酯对硫磷具有很高的反应性,2a,2b的醇羟基参与了对弱配位底物羧酸酯及磷酸酯的进攻,对不同电荷性质的羧酸酯底物具有较强的静电选择性。     

Theoretical studies on the hydrolysis of phosphate diesters in the gas phase,solution, and RNase A

Density functional theory, polarizable continuum models and semiempirical hybrid quantum mechanical/molecular mechanical (QM/MM) calculations were applied to the hydrolysis of phosphate diesters in the gas phase, in solution, and in the enzyme RNase A. Neutralization of the negative charge of the pentacovalent phosphorane intermediates provides a substantial stabilization of the transition‐state structures in the gas phase. Inclusion of solvent effects on the phosphate/phosphorane species was critical to reproducing the trends in reactivity observed experimentally. Finally, the catalytic mechanism for the hydrolysis of uridine 2′,3′‐cyclic phosphate by RNase A was studied by QM/MM calculations. Our results suggest that the rate‐limiting transition state of the reaction corresponds to the approach of a water molecule to the phosphate and its activation by His119. Thus, His119 acts as a generalized base for the reaction. The water attack leads to a pentacovalent phosphorane transition state of formal charge ?2; this excess of negative charge in the transition state is stabilized by a number of positively charged residues including His12 and Lys41. In the second stage of the reaction, the phosphorane is converted into products. This part of the reaction proceeds without a detectable barrier, and it is facilitated by a proton transfer from Lys41 to the departing O_2′. © 2001 John Wiley & Sons, Inc. Int J Quantum Chem, 2001     

Activating water: important effects of non-leaving groups on the hydrolysis of phosphate triesters

The high rate of spontaneous hydrolysis of tris-2-pyridyl phosphate (TPP) is explained by the activating effects of the non-leaving ("spectator") groups on P-OAr cleavage, and not by intramolecular catalysis. Previous work on phosphate-transfer reactions has concentrated on the contributions to reactivity of the nucleophile and the leaving group, but our results make clear that the effects of the non-leaving groups on phosphorus can be equally significant. Rate measurements for three series of phosphate triesters showed that sensitivities to the non-leaving groups are substantial for spontaneous hydrolysis reactions, although significantly smaller for reactions with good nucleophiles. There are clear differences between triaryl and dialkyl aryl triesters in sensitivities to leaving and non-leaving groups with the more reactive triaryl systems showing lower values for both β(LG) and β(NLG). Intramolecular catalysis of the hydrolysis of TPP by the neighbouring pyridine nitrogens is insignificant, primarily because of their low basicity.     

The role of hydrogen bonding in the crystal structures of zinc phosphate hydrates

The compounds alpha- and beta-hopeite have been synthesised by hydrothermal crystallisation from aqueous solution at 90 degrees C and 20 degrees C, respectively. The crystal structures of these polymorphic forms of zinc phosphate tetrahydrate (ZPT), Zn(3)(PO(4))(2).4 H(2)O, have been resolved. Single-crystal analysis proves that the main difference between the alpha and beta forms of ZPT is caused by the difference in orientation of one of the water molecules in the ZnO(6) octahedral network, indicating two different hydrogen-bonding patterns. A previously unknown hopeite, Zn(3)(HPO(4))(3).3 H(2)O (ZHPT), has been isolated and analysed. This helps to achieve a better understanding of the mechanism of formation of zinc phosphate compounds. Unambiguous identification of each phase is established by analysis of their unique thermal behaviour and thermodynamic interrelationship.     

Weak interactions between deposited metal overlayers and organic functional groups of self-assembled monolayers

The purpose of our research is to study the reactions, interactions or penetration between vacuum-deposited metals (M) and the organic functional end groups (OFGs) of self-assembled monolayers (SAMs) under controlled conditions. Metal/SAM systems are models for understanding bonding at M/organic interfaces and the concomitant adhesion between the different materials. In broad terms, the M/OFGs form interacting interfaces (e.g., Cr/COOH or Cu/COOH) in which the deposit resides on top of the OFGs or weakly interacting interfaces through which the overlayer penetrates and resides at the SAM/gold interface. We present a review of XPS results from weakly interacting systems (e.g., Cu/OH, Cu/CN, Ag/CH₃, Ag/COOH) and discuss in more depth the time-temperature dependence of the disappearance of the metal from the M/SAM interface following deposition. In this work, XPS and ISS were used to characterize octadecanethiol (ODT, HS(CH₂)₁₇CH₃), mercaptoundecanoic acid (MUA, HS(CH₂)₁₀COOH), and mercaptohexadecanoic acid (MHA, HS(CH₂)₁₅COOH) SAMs before and after depositing up to 1.0 nm Ag or Cu at ca. 10⁻⁷ torr. The SAMs were prepared by self-assembly onto gold films on <100> silicon substrates in an ethanolic thiol solution. XPS spectra indicate that no strong interaction occurs between the deposited Ag and the COOH organic functional group (OFG) of MUA or MHA, although a stronger interaction is evident for MHA, and a unidentate is formed for Cu on mercaptoundecanol (MUO). The Ag interaction with ODT is weak. ISS compositional depth profiles (CDPs) for Ag on MHA and MUA and ODT are compared over a temperature range of 113 to 293 K. The ISS results indicate that Ag remains on the surface of MUA for up to 1 h after deposition, whereas Ag penetrates ODT in less than 5 min at 295 K. The time for Ag to penetrate into MHA is several times longer than for MUA, depending on the SAM temperature. The time dependence of the slower Ag penetration through MUA and MHA is compared with that for ODT at temperatures below 295 K. Although Ag/OFGs are expected to have relatively weak interactions, the Ag/COOH system was anticipated to be more interactive than was found, so rapid penetration of Ag through the COOH SAM is an unexpected result.     

Metal-free,noncovalent catalysis of diels-alder reactions by neutral hydrogen bond donors in organic solvents and in water

We examined the catalytic activity of substituted thioureas in a series of Diels-Alder reactions and 1,3-dipolar cycloadditions. The kinetic data reveal that the observed accelerations in the relative rates are more dependent on the thiourea substituents than on the reactants or solvent. Although the catalytic effectiveness is the strongest in noncoordinating, nonpolar solvents, such as cyclohexane, it is also present in highly coordinating polar solvents, such as water. In 1,3-dipolar cycloadditions, the thiourea catalysts demonstrate only very moderate selectivity for reactions with inverse electron demand. Our experiments emphasize that both hydrophobic and polar interactions can co-exist, making these catalysts active, even in highly coordinating solvents. This class of catalysts increases the reaction rates and endo-selectivities of Diels-Alder reactions, in a similar manner to weak Lewis acids, without concomitant product inhibition.     

Interactions between organic molecules and water: rotational spectrum of the 1:1 oxetane-water complex

The 1:1 molecular complex between oxetane and water has been investigated by using free-jet millimeter-wave spectroscopy. The rotational spectra of five isotopomers (with H(2)O, D(2)O, DOH, HOD and H(2) (18)O) have been assigned. Partial r(0) and r(s) structures of the complex have been derived. The water moiety lies in the plane of symmetry of oxetane, with the "free" hydrogen E with respect to the ring. The oxetane ring appears to be slightly nonplanar, with the C(beta) carbon tilted on the opposite side of the water unity. The three atoms involved in the hydrogen bond adopt a linear arrangement with an O(ring).H distance of about 1.86 A, and the angle between the COC bisector and the O(ring).H bond being congruent with 106 degrees. Additionally, quantum-chemical calculations for the complex were performed and were found to be in agreement with the experimental results.     

煤焦表面官能团对甲烷裂解的影响

采用石英管固定床反应器,考察了1 123 K,CH_4/N_2=1∶4的状态下,煤焦表面官能团对甲烷裂解的影响。煤焦表面主要含有羟基、羰基和醚键等官能团,分别通过氢氧化钡、苯肼和碘化氢溶液对煤焦表面进行化学处理,除去煤焦表面相应的官能团,研究处理后煤焦的催化活性,得出煤焦中官能团对甲烷裂解的影响。氢氧化钡处理煤焦后,煤焦中部分羟基被氢氧化钡消耗,甲烷初始转化率和氢气初始收率分别为90.5%和65.2%,说明煤焦中的羟基不利于甲烷的裂解。通过苯肼处理煤焦中羰基并使之转化,甲烷初始转化率和氢气初始收率分别为55.4%和42.9%,说明煤焦中的羰基对甲烷裂解有利。碘化氢处理煤焦后,煤焦中的醚键转化成羟基,甲烷的转化率和氢气收率都明显下降,说明醚键的存在对甲烷裂解同样有利。随着反应时间的延长,甲烷的转化率和氢气的收率降低,催化剂逐渐失活。反应前后煤焦电镜扫描照片表明,甲烷裂解生成的积炭沉积在煤焦表面,堵塞煤焦的孔道,煤焦的比表面积减小,催化活性降低。     

Effect of oxygen-containing functional groups on the wettability of coal through DFT and MD simulation

To investigate the wettability of different oxygen-containing functional group (OFG) surfaces, graphite substrates were used as a model for coal adsorbents. The substrates were modified with COOH, OH, CO, and OCH₃. The adsorption-diffusion behavior of H₂O molecules/water droplets on different OFG surfaces was investigated using molecular dynamics (MD) simulations with frontier orbital energy difference as a metric for different surface wettability degrees in quantum chemical analysis. The results indicated that the frontier orbital energy difference of the H₂O molecule was 3.480, 3.491, 3.631, and 3.680 eV for PhCOOH, PhOH, PhCO, and PhOCH₃, respectively. In addition, the equilibrium contact angle, interaction energy, and number of hydrogen bonds after the adsorption equilibrium of water droplets for COOH, OH, CO, and OCH₃ surfaces were 22.34°, ?5.03 kcal/mol, and 652; –23.72°, ?4.19 kcal/mol, and 450; 68.01°, ?0.79 kcal/ mol, and 61; 90.51°, ?0.50 kcal/mol, and 28, respectively. The smaller the energy difference between the frontier orbitals of the H₂O molecule and the OFG, the smaller the equilibrium contact angle between the water droplet and the OFG surface, the more hydrogen bonds were formed, and the larger the absolute value of the interaction energy, the better the wettability of the surface of the OFG. The order of wettability of the different OFG surfaces was COOH > OH > CO > OCH₃, which is consistent with the radial distribution function and the analysis results for the extended area, etc. The results of density functional theory (DFT) calculations and MD simulations exhibited identical patterns, indicating the reasonableness of the simulations. This study may serve as a reference for the suppression of hydrophilicity in low-order coal and the enhancement of the flotation effect.     

Hydrogen‐Bonding in Aminocatalysis: From Proline and Beyond

This Concept article summarizes recent progress in the field of hydrogen‐bonding aminocatalysis using proline‐derived systems. The aminocatalysts available in the literature are categorized by the incorporated hydrogen‐bonding scaffold and its mode of recognition. Both mono‐ and double‐hydrogen‐bonding motifs are discussed and examples of their application in asymmetric synthesis are given.     

Steric effects of pH switchable,substituted (2-pyridinium)urea organocatalysts: a solution and solid phase study

The study of hydrogen bonding organocatalysis is rapidly expanding. Much research has been directed at making catalysts more active and selective, with less attention on fundamental design strategies. This study systematically increases steric hindrance at the active site of pH switchable urea organocatalysts. Incorporating strong intramolecular hydrogen bonds from protonated pyridines to oxygen stabilizes the active conformation of these ureas thus reducing the entropic penalty that results from substrate binding. The effect of increasing steric hindrance was studied by single crystal X-ray diffraction and by kinetics experiments of a benchmark reaction.     

胶束溶液中高氯酸二水(四胺)合钴(Ⅲ)配合物催化磷酸二酯水解的研究

本文合成了疏水性高氯酸二水（四胺）合钴（Ⅲ）配合物，研究了它与非离子表面活性剂Brij35形成的金属2胶束催化二（对硝基苯酚）磷酸二酯水解的动力学及其机理。结果表明此金属胶束对磷酸二酯水解的速率大约提高10^4倍，这主要是由于表面活性剂胶束的pH效应和浓聚效应所致，暗示着顺式二水类配合物形成的金属胶束是一个潜在的磷酸二酯水解剪切的催化剂。     

Hydrogen-bond-directed catalysis: faster, regioselective and cleaner Heck arylation of electron-rich olefins in alcohols

A general method for the regioselective Heck reaction of electron-rich olefins is presented. Fast, highly regioselective Pd-catalysed alpha-arylation of electron-rich olefins, vinyl ethers (1 a-d), hydroxyl vinyl ethers (1 e, f), enamides (1 g, h) and a substituted vinyl ether (1i) has been accomplished with a diverse range of aryl bromides (2 a-r), for the first time, in cheap, green and easily available alcohols with no need for any halide scavengers or salt additives. The reaction proceeds with high efficiency, leading exclusively to the alpha-products, in 2-propanol and particularly in ethylene glycol. In the latter, the arylation can be catalysed at a palladium loading of 0.1 mol% and finish in as short a time as 0.5 h. The remarkable performance of the alcohol solvents in promoting alpha regiocontrol is attributed to their hydrogen-bond-donating capability, which is believed to facilitate the dissociation of halide anions from PdII, and hence, the generation of a key ionic PdII-olefin intermediate responsible for the alpha product. This belief is further strengthened by the study of a benchmark arylation reaction in 21 different solvents. The study revealed that exclusive alpha-regioselective arylation takes place in almost all of the protic solvents, and there is a rough correlation between the alpha-arylation rates and the solvent parameter E(T)N. The method is simpler, cleaner and more general than those established thus far.