Characterization of peptide-pyrazole interactions in solution by low-temperature NMR studies

Complexation of the amino- and carboxyl-protected tripeptide Piv-L-Val-L-Val-L-Val-tBu with 3-methylpyrazole and 3-amino-5-methylpyrazole was studied by low-temperature NMR experiments in a freonic solvent. The peptide forms an extended beta-type structure at all temperatures and associates through hydrogen bonding with the two pyrazole-based beta-sheet ligands. A detailed structural characterization of the formed complexes by one- and two-dimensional NMR experiments under slow exchange conditions was made possible by employing very low temperatures. The tripeptide associates to stable antiparallel dimers that are symmetrically capped on both sides by two pyrazole receptors to form 2:2 complexes. Amide groups of two neighboring residues in an extended conformation are involved in cyclic hydrogen bonds to the pyrazole. Based on amide chemical shift changes, the relative strength of intermolecular hydrogen bonds can be assessed and correlated with the electronic effects of the substituents on the pyrazole.     

Effect of substitution and the counterion on the structural and spectroscopic properties of CuII complexes of methylated pyrazoles

The coordination chemistry of pyrazole and three of its methyl derivatives with the chloride and nitrate salts of copper(II) under strictly controlled reaction conditions is systematically explored to gain a better understanding of the effect of counterion coordination strength and ligand identity on the structure and electronic absorption spectra of their resulting complexes. Despite the initial 2 : 1 ligand to metal ratio in water, copper(II) nitrate forms exclusively 4 : 1 ligand to metal complexes while copper(II) chloride forms a 4 : 1 ligand to metal complex only with pyrazole, with the methyl derivatives forming 2 : 1 ligand to metal complexes, as determined by single-crystal X-ray diffraction (XRD). This is attributed to a combination of ligand sterics and stronger coordination of chloride relative to nitrate. Electronic absorption spectroscopy in both water and methanol reveals a surprisingly strong effect of the pyrazole methyl position on the Cu^II d–d transition, with 4-methylpyrazole producing a higher energy d–d transition relative to the other ligands studied. In addition, the number of methyl groups plays a determining role in the energy of the pz π→Cu^II d_xy LMCT band, lowering the transition energy as more methyl groups are added.     

Methylpyrazole-capped two-dimensional supramolecular M(II) (M = Mn, Ni, Co) assemblies constructed by covalent and noncovalent interactions: uncommon coordination modes of methylpyrazoles and magnetic properties

Two mononuclear complexes [Mn(5-methylpyrazole)4(N3)2] (1) and [Ni(5-methylpyrazole)4(N3)2] (2), as well as a novel one-dimensional coordination polymer [Co(3-methylpyrazole)2(5-methylpyrazole)2(tp)]n (3) (tp = terephthalate), were characterized. The isostructural complexes, 1 and 2, display two-dimensional supramolecular networks formed by hydrogen bonds between the N-H groups of 5-methylpyrazoles and the end N atoms of the azide ligands and additional face-to-face pi-pi interactions of the 5-methylpyrazoles. For 3, tp-bridged one-dimensional chains assisted by intrachain hydrogen bonds among the N-H groups of methylpyrazoles and carboxylate oxygens are connected with the help of interchain C-H...O hydrogen bonds, leading to a two-dimensional structure. The intra- and interchain hydrogen bonds account for the coexistence of two unique coordination forms (5-methylpyrazole and 3-methylpyrazole) of methylpyrazoles in the same coordination sphere. Weak antiferromagnetic interactions coupled with the spin-orbit coupling effect are operative in 3 through the tp ligands.     

3-卤代吡唑质子转移过程的理论研究

采用密度泛函B3LYP/6-311G**方法,对3-卤(-F、-Cl、-Br)代吡唑几何构型进行了全自由度优化,获得了它们的几何结构和电子结构。计算结果显示,N1-H型的稳定性大于N2-H型。计算并考察了3-卤代吡唑进行结构互变的质子转移过程的四种可能途径:(a)分子内质子转移;(b)水助质子转移;(c)同种二聚体双质子转移;(d)异种二聚体双质子转移。计算结果表明(以3-氟代吡唑为例),途径d所需要的活化能最小(54.89 kJ/mol),而途径a所需要的活化能最大(198.83kJ/mol),途径b和c的活化能居中间分别为(104.05 kJ/mol和69.05 kJ/mol)。研究还表明氢键在降低活化能方面起着重要的作用,卤素(-F、-Cl、-Br)对活化能的影响不大。     

pH-metric studies on formation constants of the complexes of substituted pyrazoles with some lanthanide metal ions and the influence of ionic strengths on complex equilibria in a 70% dioxane-water mixture

The pK a values of N-heterocyclic compounds (substituted pyrazoles) in a 70% (v/v) dioxane-water mixture have been determined using pH-metric measurements. The stability constants of the complexes of Dy(III), Nd(III), Sm(III), and Tb(III) with 3-(2-hydroxyphenyl)-5-methylpyrazole, l-phenyl-3-(2-hydimyphenyl)-5-methylpyrazole 3-(2-hydroxy-4-methylphenyl)-5-methylpyrazole, and l-phenyl-3-(2-hydroxy-4-methylphenyl)-5-methylpyrazole have been determined by the pH-metric method at ( 300 ± 0.1) K. The effect of ionic strengths on the complexes of Sm³⁺ and Pr³⁺ ions with pyrazole has been investigated in the internal from 0.02 to 0.1 mol dm⁻³ (sodium perchlorate) in the pH range 2–3.     

Highly efficient redox isomerisation of allylic alcohols catalysed by pyrazole-based ruthenium(IV) complexes in water: mechanisms of bifunctional catalysis in water

The catalytic activity of ruthenium(IV) ([Ru(η(3):η(3)-C(10)H(16))Cl(2)L]; C(10)H(16) = 2,7-dimethylocta-2,6-diene-1,8-diyl, L = pyrazole, 3-methylpyrazole, 3,5-dimethylpyrazole, 3-methyl-5-phenylpyrazole, 2-(1H-pyrazol-3-yl)phenol or indazole) and ruthenium(II) complexes ([Ru(η(6)-arene)Cl(2)(3,5-dimethylpyrazole)]; arene = C(6)H(6), p-cymene or C(6)Me(6)) in the redox isomerisation of allylic alcohols into carbonyl compounds in water is reported. The former show much higher catalytic activity than ruthenium(II) complexes. In particular, a variety of allylic alcohols have been quantitatively isomerised by using [Ru(η(3):η(3)-C(10)H(16))Cl(2)(pyrazole)] as a catalyst; the reactions proceeded faster in water than in THF, and in the absence of base. The isomerisations of monosubstituted alcohols take place rapidly (10-60?min, turn-over frequency = 750-3000?h(-1)) and, in some cases, at 35?°C in 60?min. The nature of the aqueous species formed in water by this complex has been analysed by ESI-MS. To analyse how an aqueous medium can influence the mechanism of the bifunctional catalytic process, DFT calculations (B3LYP) including one or two explicit water molecules and using the polarisable continuum model have been carried out and provide a valuable insight into the role of water on the activity of the bifunctional catalyst. Several mechanisms have been considered and imply the formation of aqua complexes and their deprotonated species generated from [Ru(η(3):η(3)-C(10)H(16))Cl(2)(pyrazole)]. Different competitive pathways based on outer-sphere mechanisms, which imply hydrogen-transfer processes, have been analysed. The overall isomerisation implies two hydrogen-transfer steps from the substrate to the catalyst and subsequent transfer back to the substrate. In addition to the conventional Noyori outer-sphere mechanism, which involves the pyrazolide ligand, a new mechanism with a hydroxopyrazole complex as the active species can be at work in water. The possibility of formation of an enol, which isomerises easily to the keto form in water, also contributes to the efficiency in water.     

Theoretical insights into the absorption and emission properties of blue luminescent copper(I) complexes based on the pyrazolyl‐pyridine ligands

The ground geometrical and electronic structures, charge transfer (CT) behaviors, absorption, and emission properties of the three copper(I) complexes [Cu(pypz)(POP)]⁺ (1) , [Cu(pympz)(POP)]⁺ (2) , and [Cu(pytfmpz)(POP)]⁺ (3) (pypz=1‐(2‐pyridyl)pyrazole, pympz=3‐methyl‐1‐(2‐pyridyl)pyrazole, and pytfmpz=3‐trifluoromethyl‐1‐(2‐pyridyl)pyrazole), have been investigated using density functional theory (DFT) and time‐dependent density functional theory (TD‐DFT). The vertical absorption energies of the all copper(I) complexes are well reproduced by TD‐DFT calculations based on the CT amount calculations. The triplet emission properties of the all copper(I) complexes were correctly evaluated at BMK/LANL2DZ/6‐31G* level of theory. In addition, the thermally activated delayed fluorescence properties of 1–3 were discussed in detail based on the spatial separation of the HOMO and LUMO and vertical excited energies. These theoretical insights should be expected to provide some guides for the design and synthesis of efficient luminescent copper(I) complexes. © 2014 Wiley Periodicals, Inc.     

X-ray structural and spectroscopic investigation of cyanamidonitrate nickel(II) complexes with pyrazole type ligands

New cyanamidonitrate complexes of the type [Ni(NO₂NCN)₂L₄], where L = pyrazole (pz), 3(5)-methylpyrazole (mpz), 3,5-dimethylpyrazole (dmpz), 3,4,5-trimethylpyrazole (tmpz), indazole (benzopyrazole; inz), 4-bromopyrazole (Br-pz) and 4-iodopyrazole (I-pz) have been isolated and characterized by i.r. and electronic spectroscopy. The crystal structure of [Ni(NO₂NCN)₂(pz)₄] was solved by X-ray crystallography. The Ni^II environment is practically octahedral, composed of four tertiary nitrogens from pyrazole ligands and two nitrile nitrogens from cyanamidonitrate groups. According to the spectral results similar molecular structures can be attributed to all remaining complexes. The i.r. spectra exhibit changes in the cyanamidonitrate vibrations caused by coordination of this group. The electronic spectra are in agreement with the practically octahedral Ni^II environment.     

3-羰基吡唑质子转移过程的理论研究

采用密度泛函B3LYP／6—311G^＊＊方法,对3-羰基吡唑几何构型进行了全自由度优化,获得了它们的几何结构和电子结构．计算并考察了3-羰基吡唑的两种构象即syn和anti构象的稳定性以及3-羰基吡唑进行结构互变的质子转移过程的四种可能途径：（a）分子内质子转移;（b）水助质子转移;（C）同种二聚体双质子转移;（d）异种二聚体双质子转移．计算结果表明3-羰基吡唑的syn构象中N2-H型的稳定性大于N1-H型,进行质子转移时途径（C）所需要的活化能最小（52．78kJ／mol）,途径（a）所需要的活化能最大（200．59kJ／mol）;3,羰基吡唑的。anti构象中N1-H型的稳定性大于N2-H型,进行质子转移时途径（d）所需要的活化能最小（61．09kJ／mol）,途径（a）所需要的活化能最大（204．15kJ／mol）．     

Reaction of indazole and alkylpyrazoles with acetylene

The reaction of indazole and pyrazole and its alkyl-substituted derivatives with acetylene was studied. It was established that indazole and 3(5)-methylpyrazole form a mixture of vinyl isomers corresponding to their tautomeric forms under vinylation conditions. The ratios of the isomers of vinylindazoles in the reaction mixtures depend on the nature of the catalyst. The indazole isomers were separated by gas-liquid chromatography, and the 3(5)-methylpyrazole isomers were separated by vacuum fractionation. 1-Di(1-pyrazolyl)ethanes, the structure of which was confirmed by their PMR spectra, are also formed in the vinylation of pyrazoles.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1247–1251, September, 1976.     

Synthesis,crystal structure and photophysical study of luminescent three-coordinate cuprous bromide complexes based on pyrazole derivatives

The 1?:?2 M-ratio reaction between cuprous bromide and pyrazole derivatives in toluene results in mononuclear Cu(I) complexes [CuBr(pyrazole)₂]. The complexes have been characterized by ¹H NMR spectroscopy and elemental analysis. The molecular structure, established by single-crystal X-ray diffraction, features a trigonal planar geometry around copper, with monodentate pyrazole derivatives. All the Cu(I) complexes are luminescent in the solid state at ambient temperature. Intense blue or blue-green emission in the solid state is observed for these complexes, with the maxima ranging from 431 to 493 nm. The observed photoluminescence could be ascribed to the metal-to-ligand charge-transfer excited states, probably mixed with some halide-to-ligand character. The microsecond lifetime scale of the complexes implies that these transitions arise from the triplet excited states.     

Spectrophotometric study on the charge transfer reaction between 2-amino-4-methylpyridine with chloranilic acid in polar solvents

Charge transfer (CT) complexes formed between 2-amino-4-methylpyridine as electron donor, chloranilic acid as electron acceptor was investigated spectrophotometrically in acetonitrile (AN), methanol (MeOH) and binary mixture of acetonitrile 50% + methanol 50% (MeOH-AN). Minimum–maximum absorbance method has been used for estimating the formation constants of the CT reactions (K_CT). Job’s method of continuous variation and photometric titration studies were used to detect the stoichiometric ratios of the formed complexes, and they showed that 1:1 complexes were produced. The molar extinction coefficient (e), oscillator strength (f), dipole moment (l), CT energy (E_CT), ionisation potential (I_P) and the dissociation energy (W) of the formed complexes were estimated; they reached acceptable values suggesting the stability of the formed CT complexes. The solid CT complexes were synthesised and characterised by elemental analyses, ¹H NMR and FTIR spectroscopies where the formed complexes included proton and electron transfer.     

Charge transfer complexes of 9-vinyl-carbazole with pi acceptors in homogeneous and in micellar solutions

The molecular association of 9-vinyl-carbazole (CBZ) with three electron acceptors, p-chloranil (CHL), 2,7-dinitro-9-fluorenone (FL), and tetracyano-p-quinodimethane (TCNQ), is studied in acetonitrile and in micellar aqueous solution of sodium dodecyl sulfate (SDS). In both media, stable charge transfer (CT) complexes are formed with association constants in the range of 8-500 M(-1). CBZ and FL form a 1:2 complex in acetonitrile, but in SDS micelles the association is 1:1 due to size restriction and occupancy statistics in the host aggregates. The combination of absorption and fluorescence emission spectroscopy data indicates that the bimolecular CT complex of CBZ with TCNQ is stabilized in two distinct environments of the SDS micelles providing then two separated CT absorption bands.     

Infrared and ab initio studies of hydrogen bonding and proton transfer in the complexes formed by pyrazoles

The results of experimental studies and quantum mechanical calculations of vibrational spectra and structure of hydrogen bonded complexes formed by pyrazole (P) and 3,5-dimethylpyrazole (DMP) are presented. IR spectra of pyrazoles in solutions, gas phase, and solid state have been investigated in wide range of concentrations and temperatures. It has been found that in the gas phase both P and DMP reveal the equilibrium between monomers, dimers, and trimers. In solutions the equilibrium between monomers and trimers dominates, no bands, which can be attributed to dimers were detected. DMP retains the trimer structure in solid state, while in the case of pyrazole P, formation of the crystal provides another type of association. Geometrical and spectral characteristics of dimers and trimers, obtained by ab initio calculations, are presented and compared with experimental data.

IR spectra of solutions containing P and DMP with a number of acids (acetic and trifluoroacetic acids, pentachlorophenol, HBr) have been studied in parallel with ab initio calculations. It has been found that pentachlorophenol forms with pyrazoles complexes with one strong hydrogen bond O–HN, while NH pyrazole group remains unbonded. With carboxylic acids DMP forms 1:1 cyclic complexes with two hydrogen bonds. In the case of acetic acid, the complex in CH₂Cl₂ solution reveals molecular structure with OHN and C=OHN bonds, in accordance with results of the calculations. For trifluoroacetic acid, the calculations predict the molecular structure to be energetically more stable in the case of the isolated binary complex (in gas phase), while the experimental spectrum of CH₂Cl₂ solution gives an evidence of the proton transfer with formation of the cyclic ionic pair with two NH⁺O⁻ bonds. The agreement with experimental results can be improved by taking into account the influence of environment in the framework of Onsager or Tomasi models. The shape of proton potential function of the complexes and medium effect on its parameters, resulted from experimental data and calculations, are discussed. It has been found that the number of potential minima and their relative depth depend strongly on the method of calculations and the basic set. Under excess of trifluoroacetic acid, the formation of 2:1 acid–DMP complex has been detected. Spectral characteristics and results of calculations point to the cyclic structure of this complex, which includes homoconjugated bis-trifluoroacetate anion and DMPH⁺ cation. With HBr both studied pyrazoles were found to form ionic complexes including one or two pyrazole molecules per one acid molecule and correspondingly monocation or homoconjugated cation BHB⁺.     

Syntheses of substituted 1-(2-phenethyl)pyrazoles

Alkylation of 3-methylpyrazole with 2-phenethyl p-toluenesulfonate gave 3-methyl-1-(2-phenethyl)pyrazole ( 2a ) and 5-methyl-1-(2-phenethyl)pyrazole ( 3a ) in low yield. Reaction of 5-chloro-1,3-dimethylpyrazole ( 5 ) with substituted-benzaldehydes afforded compounds 7 . Reduction of the latter afforded compound 2 in high yield. Compound 3 could be obtained from the reaction of substituted-2-(phenethyl)hydrazine hydrochloride 9 with acetoacetaldehyde dimethylacetal in moderate yield.     

蝎型钒氧苯甲酸配合物的合成、结构及量化计算

设计合成了两种以聚吡唑硼酸盐、苯甲酸为配体的钒氧配合物VO[HB(pz)3](pzH)(C6H5COO)(1)和VO[HB(3,5-Me2pz)3](3,5-Me2pzH)(C6H5COO)(2)((HB(pz)3: 聚吡唑硼酸钠盐; pzH: 吡唑; HB(3,5-Me2pz)3: 聚甲基吡唑硼酸钠盐; 3,5-Me2pzH: 3,5-二甲基吡唑). 通过元素分析、红外光谱和X射线单晶衍射方法对配合物进行了表征. 并结合从头计算结果进一步分析了配合物的稳定性及分子中配键的共价特征. 分析结果表明, 配合物2的稳定性大于配合物1, 中心钒原子周围的价键类型都属于共价键范畴, 键序分析结果与晶体结构测定的键长结果是一致的.     

Crystallographic and spectroscopic studies on palladium(II) complexes containing pyrazole and thiocyanate ligands

Mononuclear palladium(II) complexes containing both pyrazole-type ligands and thiocyanate, of general formula [Pd(SCN)₂(L)₂] {L = pyrazole (HPz) and 1-phenyl-3-methylpyrazole (phmPz)} have been prepared and characterized by elemental analysis, i.r. and n.m.r. spectroscopy and by single crystal X-ray diffraction methods. The Pd atom in these structures lies on the crystallographic inversion center; in a square-planar coordination geometry made by two sulfur and two nitrogen atoms of the ligands, both in trans positions.     

Dopamine interaction in the absence and in the presence of Cu2+ ions with macrocyclic and macrobicyclic polyamines containing pyrazole units. Crystal structures of [Cu2(L1)(H2O)2](ClO4)4 and [Cu2(H-1L3)](ClO4)3*2H2O.

The interaction with Cu2+ and dopamine of three polyazacyclophanes containing pyrazole fragments as spacers is described. Formation of mixed complexes Cu2+-macrocycle-dopamine has been studied by potentiometric methods in aqueous solution. The crystal structures of the complexes [Cu2(L1)(H2O)2](ClO4)4*2H2O (4) (L1 = 13,26-dibenzyl-3,6,9,12,13,16,19,22,25,26-decaazatricyclo[22.2.1.1(11,14)]octacosa-1(27),11,14(28),24-tetraene) and [Cu2(H-1L3)](HClO4)(ClO4)2*2H2O (6) (L3 = 1,4,7,8,11,14,17,20,21,24,29,32,33,36-tetradecaazapentacyclo[12.12.12.1(6,9).1(19,22).1(31,34)]hentetraconta-6,9(41),19(40),21,31,34(39)-hexaene) are presented. In the first one (4), each Cu2+ coordination site is made up by the three nitrogens of the polyamine bridge, a sp2 pyrazole nitrogen and one water molecule that occupies the axial position of a square pyramid. The distance between the copper ions is 6.788(2) A. In the crystal structure of 6, the coordination geometry around each Cu2+ is square pyramidal with its base being formed by two secondary nitrogens of the bridge and two nitrogen atoms of two different pyrazolate units which act as exobidentate ligands. The axial positions are occupied by the bridgehead nitrogen atoms; the elongation is more pronounced in one of the two sites [Cu(1)-N(1), 2.29(2) A; Cu(2)-N(6), 2.40(1) A]. The Cu-N distances involving the deprotonated pyrazole moieties are significantly shorter than those of the secondary nitrogens. The Cu(1)...Cu(2) distance is 3.960(3) A. The pyrazole in the noncoordinating bridge does not deprotonate and lies to one side of the macrocyclic cavity. One of the aliphatic nitrogens of this bridge is protonated and hydrogen bonded to a water molecule, which is further connected to the sp2 nitrogen of the pyrazole moiety through a hydrogen bond. The solution studies reveal a ready deprotonation of the pyrazole units induced by coordination to Cu2+. In the case of L2 (L2 = 3,6,9,12,13,16,19,22,25,26-decaazatricyclo[22.2.1.1(11,14)]octacosa-1(27),11,14(28),24-tetraene), deprotonation of both pyrazole subunits is already observed at pH ca. 4 for 2:1 Cu2+:L2 molar ratios. All three free receptors interact with dopamine in aqueous solution. L3 is a receptor particularly interesting with respect to the values of the interaction constants over five logarithmic units at neutral pH, which might suggest an encapsulation of dopamine in the macrocyclic cage. All three receptors form mixed complexes Cu2+-L-dopamine. The affinity for the formation of ternary dopamine complexes is particularly high in the case of the binuclear Cu2+ complexes of the 1-benzyl derivative L1.     

Synthesis of <Emphasis Type="Italic">N</Emphasis>-vinylazoles from vinyl acetate without using mercury catalysts

N-Vinyl-substituted pyrazole, 3(5)-methylpyrazole, imidazole, and 1,2,4-triazole were synthesized by addition of the corresponding azoles to vinyl acetate under conditions of phase-transfer catalysis, followed by pyrolysis of N-(1-acetoxyethyl)azoles thus formed at 350–400°C in the presence of water.     

Electrochemistry of copper complexes with macrocyclic polyamines containing pyrazole units

The voltammetric behaviour of bi- and mono-nuclear complexes formed in solution by Cu(2+) with three polyazacyclophanes containing pyrazole units in aqueous solution is described. Cyclic and square wave voltammetric responses at glassy carbon electrodes indicate that the reduction of copper-macrocycle complexes in solution takes place in two successive one-electron per Cu transfer processes coupled with preorganization and protonation reactions that mimic the behaviour of superoxide dismutase. The electrochemistry of ternary Cu(2+)-receptor-dopamine complexes exhibits significant differences with respect to the protection of the neurotransmitter from post-electron transfer cyclization reactions.