Imidazole NH Groups Research Articles

Partially methylated polybenzimidazoles as coating for alkaline zinc anodes

Hydroxide ion conductive polymer coatings with a low permeability for zinc species reduce shape change and dendrite formation of zinc anodes, and reduce the capacity fade over charge/discharge cycles. Herein we focus on the material properties and aim to minimize the permeability of polybenzimidazole (PBI) for zincate ions by methylating its imidazole NH groups. This reduces the volume swelling in 4 M KOH solution from 104% for PBI to 20% for a PBI with 1.3 methyl groups per repeat unit. Similarly, materials with a degree of methylation (DOM) between 0.96 and 1.2 show very low uptake of KOH. Above a DOM of 1.7 decreasing alkaline stability is observed, presumably because a fraction of the imidazole groups is permethylated to benzmidazolium ions. Most importantly, membranes with a DOM around 1–1.2 revealed the lowest permeation for zincate ions, with permeability coefficients P of 0.9–1.5 10−9 cm2 s−1, 3000 times lower than for PBI. At higher DOM slightly higher P values were observed. In a Zn/NiOOH cell an optimized anode coating with 0.96MePBI led to better cycling stability than with PBI, and an initial capacity of 265 mAh (g anode)−1.

Mobility of Histidine Side Chains Analyzed with 15N NMR Relaxation and Cross-Correlation Data: Insight into Zinc-Finger-DNA Interactions.

Due to chemical exchange, the mobility of histidine (His) side chains of proteins is typically difficult to analyze by NMR spectroscopy. Using an NMR approach that is uninfluenced by chemical exchange, we investigated internal motions of the His imidazole NH groups that directly interact with DNA phosphates in the Egr-1 zinc-finger-DNA complex. In this approach, the transverse and longitudinal cross-correlation rates for 15N chemical shift anisotropy and 15N-1H dipole-dipole relaxation interference were analyzed together with 15N longitudinal relaxation rates and heteronuclear Overhauser effect data at two magnetic field strengths. We found that the zinc-coordinating His side chains directly interacting with DNA phosphates are strongly restricted in mobility. This makes a contrast to the arginine and lysine side chains that retain high mobility despite their interactions with DNA phosphates in the same complex. The entropic effects of side-chain mobility on the molecular association are discussed.

Selective colorimetric sensing of fluoride ion via H-bonding in 80% aqueous solution by transition metal chelates

A series of four coordinated transition metal chelates of composition [M(R1)2], where M=Cu(II), Co(II), Ni(II) and Zn(II) and R1=quinone-imidazole ensemble, have been prepared and characterized by using standard analytical and spectral techniques. These metal chelates selectively (over many anions) and sensitively (detection limit down to nM) sense fluoride ion colorimetrically with an instantaneous striking colour change from yellow to red. They do so in H2O:DMF (80:20% v/v) medium, while free R1 imparts similar colour change only in DMF. The mechanism of sensing involves formation of H-bond between imidazole NH group and fluoride ion. The chelates binds strongly (Ka 107M−1) with fluoride ion to form a 1:2 (receptor:fluoride) complex. The coordination of transition metals to R1 not only enhances the H-bond donor ability of the NH group but also accommodates 80% of water in the sensing medium, which is a novel finding. Electrochemical and theoretical calculations have also been used to substantiate the results obtained in the spectral studies. The spectral data were applied to construct logic gate at molecular level.

Probing conformational propensities of histidine in different protonation states of the unblocked glycyl‐histidyl‐glycine peptide by vibrational and NMR spectroscopy

Histidine has been shown to play a major role in a number of biological systems. Being able to understand unconstrained conformational distributions of histidine and their dependence on the environment can shed light on the structure–function relation with regard to its multiple roles in biochemical processes such as proton transfer, ligand binding, protein folding and maintaining protein intrinsic disorder. We utilized polarized Raman, FTIR, vibrational circular dichroism and 1H NMR spectroscopy to probe the conformational distribution of the central histidine in the unblocked tripeptide H‐Gly‐His‐Gly‐OH in D2O. Our results show that in the double protonated state (GHG++), 94% of the histidine residue resides in the upper left quadrant of the Ramachandran plot with an equal partition between polyproline II (pPII) and β‐strand conformations. In this protonation state, enthalpic and entropic differences between the two conformations are practically eliminated, which indicates reduced backbone and/or side chain hydration. On the contrary, the single protonated state (GHG+), while only marginally different with regard to the pPII/β partition at room temperature (β‐strand is now slightly favored), shows an enthalpic stabilization of pPII by 43.02 kJ/mol, which is being compensated by an entropic stabilization of β‐strand (0.145 kJ/(mol K)). This indicates a much stronger coupling between peptide and water. At neutral pH, where the imidazole side chain of the histidine residue is deprotonated, GHG in D2O forms a hydrogel above a peptide concentration of approximately 25 mm. Some experimental evidence suggests that the preceding peptide aggregation involves hydrogen bonding between the C‐terminal groups and the imidazole NH group. Copyright © 2016 John Wiley & Sons, Ltd.

Synthesis, structures, and magnetic properties of iron(II) complexes, [FeII(HLMe)2](ClO4)2 and its ethanol adduct [FeII(HLMe)2](ClO4)2·EtOH (HLMe = 2-methylimidazol-4-yl-methylideneamino-2-ethylpyridine): Their structural distortion and spin states

Two new iron(II) complexes, [FeII(HLMe)2](ClO4)2 (1) and its ethanol adduct [FeII(HLMe)2](ClO4)2·EtOH (2) were synthesized by selective crystallization in methanol and ethanol, respectively, where HLMe is a tridentate N3 ligand, 2-methylimidazol-4-yl-methylideneamino-2-ethylpyridine, and their structures and magnetic properties were investigated. Each compound contains the same octahedrally N6 coordinated complex-cation [FeII(HLMe)2]2+ and two ClO4− ions. The non-solvated compound 1 is the HS (S=2) complex without spin transition over the 5–300K temperature range, and has the homochiral 1D helical-chain structure constructed of the intermolecular NH···O− hydrogen bonds between ClO4− ions and neighboring imidazole NH groups of the [FeII(HLMe)2]2+ cations. The ethanol adduct 2 shows a gradual one-step spin transition between the HS (S=2) and LS (S=0) states, and has two crystallographically independent iron(II) sites with two NH(imidazole)···OH(EtOH)···O(ClO4−) hydrogen bonds of Fe(1) site and two NH(imidazole)···O(ClO4−) hydrogen bonds of Fe(2) site. There are no further intermolecular interactions to produce an extended structure in a crystal lattice of 2. The presence or absence of thermal spin transition is related to the structural distortion of each HS molecule of these perchlorate salts associated with their surroundings of intermolecular hydrogen bonds.

Effect of the Crystal Packing and LIESST Effect of a Two-Dimensional Iron(II) Spin-Crossover Complex: [FeII(HLH,Me)2](CF3SO3)2 (HLH,Me: 8-(Imidazol-4-ylmethylideneamino)-2-methylquinoline)

Abstract A 2D iron(II) spin-crossover (SCO) complex, [FeII(HLH,Me)2](CF3SO3)2, was synthesized, where HLH,Me: 8-(imidazol-4-ylmethylideneamino)-2-methylquinoline, and its structures and magnetic properties were investigated. The complex [FeII(HLH,Me)2](CF3SO3)2 has no crystal solvent and has structure isomorphous to the complex [FeII(HLH,Me)2](ClO4)2·1.5MeCN, and shows a gradual and reversible one-step SCO between the HS (S = 2) and LS (S = 0) states at T1/2 = 215 K without hysteresis. The T1/2 value is higher than that of corresponding desolvated ClO4− compound, [FeII(HLH,Me)2](ClO4)2, about 35 K, although the spin transition is more gradual than that of ClO4− compound and the hysteresis is absent, which is observed in ClO4− compound. The crystal structures were determined at 296 (HS state) and 100 K (LS state), where the crystal system and space group showed no change between these temperatures. The structures at both temperatures have the same 2D layered structure, which is constructed of both the bifurcated NH···O− hydrogen bonds between two CF3SO3− ions and two neighboring imidazole NH groups of the [FeII(HLH,Me)2]2+ cations and the π–π interactions between the two quinolyl rings of the two adjacent cations. This network structure is the same as that of ClO4− compound. 600 nm light irradiation at 10 K induced the LIESST effect.

Layered iron(II) spin crossover complex constructed by NH⋯Br− hydrogen bonds with 2 K wide thermal hysteresis, [FeIIH3LMe]Br·CF3SO3 (H3LMe = tris[2-(((2-methylimidazol-4-yl)methylidene)amino)ethyl]amine)

A series of compounds [FeIIH3LMe]Br·Y·nMeOH (Y=PF6- (1), AsF6- (2), SbF6- (3), CF3SO3- (4); n=0 or 1) were synthesized, where H3LMe is a hexadentate N6 tripodal ligand of the neutral form, tris[2-(((2-methylimidazol-4-yl)methylidene)amino)ethyl]amine, and their structures and magnetic properties were investigated. The compounds 1−3 with counter anions Y=PF6-, AsF6-, and SbF6- contain methanol as a crystal solvent, and show no SCO behaviors, while the corresponding Cl− compounds have no crystal solvent and show a variety of SCO behaviors. The compound [FeIIH3LMe]Br·CF3SO3 (4) has no crystal solvent and has isomorphous structure to the Cl− compounds, and shows an abrupt spin transition between the HS (S=2) and LS (S=0) states with a hysteresis about 2K and large frozen-in effect below 72K. The T1/2↑ and T1/2↓ values are 98 and 96K, whose values are higher than those of corresponding Cl− compound about 15K and the width of hysteresis is narrower than that of corresponding Cl− compound about 2K. The crystal structures of 4 were determined at 296 and 93K, where the crystal system and space group showed no change between these temperatures. The structures at both temperatures have a same 2D layered structure, which is composed of NH⋯Br− hydrogen bonds between the Br− ion and the imidazole NH groups of three neighboring cations [FeIIH3LMe]2+. This network structure is the same as that of corresponding Cl− compound. The 600nm light irradiation at 5K induced the LIESST effect.

Poly[bis(μ-benzene-1,4-dicarboxylato)bis[μ-6-(4-pyridyl)-5H-imidazolo[4,5-f][1,10]phenanthroline]dilead(II)]: an interpenetrating α-Po net

The asymmetric unit of the title compound, [Pb(2)(C(8)H(4)O(4))(2)(C(18)H(11)N(5))(2)](n), contains two Pb(II) atoms, two benzene-1,4-dicarboxylate (1,4-bdc) dianions and two 6-(4-pyridyl)-5H-imidazolo[4,5-f][1,10]phenanthroline (L) ligands. Each Pb(II) atom is eight-coordinated by three N atoms from two different L ligands and five carboxylate O atoms from three different 1,4-bdc dianions. The two 1,4-bdc dianions (1,4-bdc(1) and 1,4-bdc(2)) show different coordination modes. Each 1,4-bdc(1) coordinates to two Pb(II) atoms in a chelating bis-bidentate mode. Each carboxylate group of the 1,4-bdc(2) anion connects two Pb(II) atoms in a chelating-bridging tridentate mode to form a dinuclear unit. Neighbouring dinuclear units are connected together by the aromatic backbone of the 1,4-bdc dianions and the L ligands into a three-dimensional six-connected alpha-polonium framework. The most striking feature is that two identical three-dimensional single alpha-polonium nets are interlocked with each other, thus leading directly to the formation of a twofold interpenetrated three-dimensional alpha-polonium architecture. The framework is held together in part by strong N-H...O hydrogen bonds between the imidazole NH groups of the L ligands and the carboxylate O atoms of 1,4-bdc dianions within different alpha-polonium nets.

Crystal structure and synthesis of benzimidazole substituted acrylonitriles and benzimidazo[1, 2-a]quinolines

The benzimidazole compounds and benzoannulated cyclic benzimidazole analogues, such as benzimidazo[1,2-a]quinolines, are a part of our wider investigation on biologically active compounds, potential antitumor drugs. Here, we present the synthesis of two compounds, [2-(1H-benzimidazol-2-yl)-3-(4-bromophenyl)-acrylonitrile, 5] and [2-bromo-benzimidazo[1,2-a]quinoline-6-carbonitrile, 7] and their crystal structures revealed by X-ray single crystal diffractometry. We also report the molecular and crystal structures of two additional compounds [2-(1H-benzimidazol-2-yl)-3-(4-cyanophenyl)-acrylonitrile, 4] and [benzimidazo[1,2-a]quinoline-2,6-dicarbonitrile, 6], whose synthesis and spectroscopic characterization have been published earlier by us too (Hranjec and Karminski-Zamola, Molecules 12:1817, 2007). The compounds 4 and 5 crystallize as monohydrates. The dihedral angles calculated between phenyl and benzimidazole ring reflect not significant deviation from molecular planarity in the crystalline state for 4 and 5, while benzoannulated cyclic benzimidazole derivatives 6 and 7 are essentially planar. The crystal structures of 4 and 5 are characterized by O–H···N and N–H···O hydrogen bonds between water molecule of crystallization and imidazole NH group as well as CN group, while in 6 and 7 only weak C–H···N intermolecular hydrogen bonds exist. Although, crystal packings are analogous in 4 and 5, the molecular conformations differ slightly. In 6 there is one C–H···N hydrogen bond that do not exist in 7.

Cobalt(III) Complexes of a Tripodal Ligand Containing Three Imidazole Groups: Properties and Structures of Racemic and Optically Active Species

AbstractThe complex [Co(H3L)](ClO4)3·H2O (1), where H3L {tris[2‐(4‐imidazoylmethylideneamino)ethyl]amine} is a tripodal ligand obtained by condensation of tris(2‐aminoethyl)amine and 4‐formylimidazole in a 1:3 molar ratio, was synthesized and optically resolved by fractional crystallization of the diastereomeric salt with [Sb2{(R,R)‐tart}2]2– [(R,R)‐tart = (2R,3R)‐tartrate(4–) ion]. From the less soluble part, Λ‐[Co(H2L)][Sb2{(R,R)‐tart}2]·4H2O (2) was isolated. Starting from 2, two optically active complexes, Λ‐[Co(H3L)](ClO4)3·1.5H2O (Λ‐1) and Λ‐[Co(L)] (Λ‐3), were obtained. The crystal structures of these complexes are compared with those of the racemic structures. Λ‐1 shows an unusually strong circular dichroism (λ = 488 nm, Δϵ = –7.74 M–1 cm–1) in the first d–d absorption band region. The effects of deprotonation–reprotonation of the uncoordinated imidazole NH groups of Λ‐[Co(H3L)]3+ on the UV/Vis and CD spectra and on the cyclic voltammograms were studied in methanol. Although the deprotonation–reprotonation reactions are reversible, the redox couple for the completely deprotonated species [CoIII/II(L)]0/– is not observed. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

{Tris[2-(imidazol-2-ylmethyl-imino)eth-yl]methyl-ammonium}iron(II) tris-(per-chlorate) dihydrate.

The title complex, [Fe(C19H27N10)](ClO4)3·2H2O, is a new polymorph of an iron(II) Schiff base complex of tris­(2-amino­ethyl)methyl­ammonium with imidazole-2-carboxaldehyde. The octa­hedral FeII atom is bound to three facial imidazole N atoms with average Fe—Nimidazole and Fe—Nimine bond distances of 1.963 (5) and 1.951 (5) Å, respectively. The central N atom of the tripodal ligand is outside the bonding distance at 3.92 Å. The crystal packing is stabilized by the hydrogen-bonding inter­actions between the two water mol­ecules (acceptor) and two of the three imidazole NH groups (donor). The third imidazole NH group (donor) forms a hydrogen bond to one of the three perchlorate counter-ions (acceptor).

Chiral Recognition and Conglomerate Crystallization Induced by Self-Organization of Cobalt(III) Complexes of a Tripodal Ligand Containing Three Imidazole Groups

The effect of a counteranion on chiral recognition inducing conglomerate crystallization of a cobalt(III) complex is reported. An achiral tripodal ligand involving three imidazole groups, tris{[2-{(imidazol-4-yl)methylidene}amino]ethyl}amine (H3L), was prepared by condensation of tris(2-aminoethyl)amine and 4-formylimidazole in a 1:3 mole ratio. The reaction of H3L and trans-[CoIIICl2(py)4]+ afforded the chiral (Delta or Lambda) [CoIII(H3L)]3+ complex. The formally hemideprotonated complexes [CoIII(H(1.5)L)]X(1.5).nH2O (where X = Cl, Br, I, BF4, ClO4, or PF6) were synthesized by controlled deprotonation of the uncoordinated imidazole NH groups of [Co(H3L)]3+. In crystals of the hemideprotonated complex, two components, [Co(H3L)]3+ and [Co(L)], with the same absolute configuration are linked by imidazole-imidazolate hydrogen bonds to form an extended homochiral 2D sheet structure, which is composed of a hexanuclear unit with a trigonal void. There are two ways of stacking the sheets: One is via homochiral stacking, and the other is via heterochiral stacking. When the size of the counterion is small (i.e., X = Cl, Br, I, or BF4), adjacent homochiral sheets with the same chirality are stacked to form a homochiral crystal (conglomerate). With large anions (i.e., ClO4- and PF6-), a homochiral sheet consisting of Delta enantiomers and a sheet consisting of Lambda enantiomers are stacked alternately to give a heterochiral crystal (a racemic crystal). Optically active Lambda-[Co(H(1.5)L)](ClO4)(1.5).H2O was synthesized from Lambda-[Co(H3L)]3+, and the crystal structure was compared to that of the racemic complex. There are two conflicting factors governing the crystal structure: the skeletal density; the size of the channels. The 2D sheets are more closely packed in the homochiral crystal than in the heterochiral crystal. However, the channels, where the counterions are accommodated, are smaller in the homochiral crystal, and the steric congestion between the anions increases with increasing anion size. The heterochiral crystal has a flexible, zigzag channel structure, and the size of the channels can increase to accommodate larger anions. Thus, complexes with large anions (i.e., ClO4- and PF6-) preferentially form heterochiral crystals rather than homochiral crystals.

A model for glutathione binding and activation in the fosfomycin resistance protein, FosA

The genomically encoded fosfomycin resistance protein from Pseudomonas aeruginosa (FosAPA) utilizes Mn(II) and K+ to catalyze the addition of glutathione (GSH) to C1 of the antibiotic rendering it inactive. Although this protein has been structurally and kinetically characterized with respect to the substrate, fosfomycin, questions remain regarding how the enzyme binds the thiol substrate, GSH. Computational studies have revealed a potential GSH binding site in FosAPA that involves six electrostatic or hydrogen-bonding interactions with protein side-chains as well as six additional residues that contribute van der Waals interactions. A strategically placed tyrosine residue, Y39, appears to be involved in the ionization of GSH during catalysis. The Y39F mutant exhibits a 13-fold reduction of catalytic activity (kcat=14±2s−1), suggesting a role in the ionization of GSH. Mutation of five other residues (W34, Q36, S50, K90, and R93) implicated in ionic of hydrogen-bonding interactions resulted in enzymes with reduced catalytic efficiency, affinity for GSH, or both. The mutant enzymes were also found to be less effective resistant proteins in the biological context of Escherichia coli. The more conservative W34H mutant has native-like catalytic efficiency suggesting that the imidazole NH group can replace the indole group of W34 that is important for GSH binding. In the absence of co-crystal structural data with the thiol substrate, these results provide important insights into the role of GSH in catalysis.

Two-Dimensional Iron(II) Spin Crossover Complex Constructed of Bifurcated NH···O-Hydrogen Bonds and π−π Interactions: [FeII(HLH,Me)2](ClO4)2·1.5MeCN (HLH,Me= Imidazol-4-yl-methylidene-8-amino-2-methylquinoline)

A 2D iron(II) spin crossover complex, [FeII(HLH,Me)2](ClO4)2.1.5MeCN (1), was synthesized, where HLH,Me = imidazol-4-yl-methylidene-8-amino-2-methylquinoline. 1 showed a gradual spin transition between the HS (S = 2) and LS (S = 0) states from 180 to 325 K within the first warming run from 5 to 350 K, in which 1.5MeCN is removed, and there was an abrupt spin transition at T1/2 downward arrow = 174 K in the first cooling run from 350 to 5 K. Following the first cycle, the compound showed an abrupt spin transition at T1/2 upward arrow = 185 K and T1/2 downward arrow = 174 K with 11 K wide hysteresis in the second cycle. The crystal structures of 1 were determined at 296 (an intermediate between the HS and LS states) and 150 K (LS state). The structure consists of a 2D extended structure constructed of both the bifurcated NH...O- hydrogen bonds between two ClO4- ions and two neighboring imidazole NH groups of the [FeII(HLH,Me)2]2+ cations and the pi-pi interactions between the two quinolyl rings of the two adjacent cations. Thermogravimetric analysis showed that solvent molecules are gradually eliminated even at room temperature and completely removed at 369 K. Desolvated complex 1' showed an abrupt spin transition at T1/2 upward arrow = 180 K and T1/2 downward arrow = 174 K with 6 K wide hysteresis.

A Variety of Spin‐Crossover Behaviors Depending on the Counter Anion: Two‐Dimensional Complexes Constructed by NH⋅⋅⋅Cl− Hydrogen Bonds, [FeIIH3LMe]Cl⋅X (X = PF6−, AsF6−, SbF6−, CF3SO3−; H3LMe = Tris[2‐{[(2‐methylimidazol‐4‐yl)methylidene]amino}ethyl]amine)

A family of spin-crossover (SC) complexes, [Fe(II)H(3)L(Me)]Cl.X (X(-) = PF(6) (-), AsF(6) (-), SbF(6) (-), CF(3)SO(3) (-)), 1-4, has been synthesized, in which H(3)L(Me) denotes the hexadentate N(6) tripod-like ligand tris[2-{[(2-methylimidazol-4-yl)methylidene]amino}ethyl]amine, containing three imidazole groups, with a view to establishing the effect of the counter anion on the SC behavior. These complexes have been found to crystallize in the same monoclinic crystal system with similar cell dimensions. The general crystal structure consists of a two-dimensional (2D) extended network constructed by NH...Cl- hydrogen bonds between Cl- and the imidazole NH groups of three neighboring [Fe(II)H(3)L(Me)]2+ ions, while the anion X exists as an isolated counter anion and occupies the space between the 2D sheets. Magnetic susceptibilities and Mössbauer spectra have revealed a variety of SC behaviors depending on the counter anion, including a one-step HS<==>(HS + LS)/2 (1, X = PF(6) (-)), a two-step HS<==>(HS + LS)/2<==>LS with a slow thermal relaxation (2, X = AsF(6) (-)), a gradual one-step HS<==>LS (3, X = SbF(6) (-)), and a steep one-step HS<==>LS with hysteresis (4, X = CF(3)SO(3) (-)). The complexes assume the space group P2(1)/n in the HS state, P2(1) in the HS + LS state, and P2(1)/n in the LS state. The Fe-N bond lengths and the N-Fe-N bond angles are indicative of the HS, HS + LS, and LS states. The molecular volumes, V, of the counter anions have been evaluated by quantum-chemical calculations as follows: 53.4 A(3) (BF(4) (-)), 54.4 A(3) (ClO(4) (-)), 73.0 A(3) (PF(6) (-)), 78.5 A(3) (AsF(6) (-)), 88.7 A(3) (SbF(6) (-)), and 86.9 A(3) (CF(3)SO(3) (-)). The size and shape of the counter anion affects the flexible 2D network structure constructed by the hydrogen bonds, leading to modifications of the SC behavior. These estimated relative sizes of the counter anions correlate well with the observed SC behaviors.

Diaquatetraimidazolecobalt(II) dibromide

In the title compound, [Co(C3H4N2)4(H2O)2]Br2, the Co atom is situated on an inversion center. It is coordinated by four N atoms of four imidazole ligands and two O atoms of water mol­ecules and has an octa­hedral geometry. In the crystal structure, water mol­ecules, imidazole NH groups and Br atoms contribute to the formation of a three-dimensional hydrogen-bonded network.

Hexakis(1H-imidazole-κN3)cobalt(II) dichloride tetrahydrate

In the title compound, [Co(C3H4N2)6]Cl2·4H2O, the CoII atom is situated on an inversion center. It is coordinated by six N atoms of six imidazole ligands and has a slightly distorted octahedral geometry. In the crystal structure, the Cl atoms, the water mol­ecules of crystallization and the imidazole NH groups contribute to the formation of a three-dimensional hydrogen-bonded network.

Molecular Dynamics Simulations of Bovine Cathepsin B and Its Complex with CA074.

To promote our better understanding of the dynamic stability of the bovine cathepsin B structure, which is characterized by an extra disulfide bond at Cys148-Cys252 from the other species, and of the binding stability of CA074 (a cathepsin B-specific inhibitor), molecular dynamics (MD) simulations were performed for the enzyme and its CA074 complex, assuming a system in aqueous solution at 300 K. The MD simulation covering 400 ps indicated that the existence of a Cys148-Cys252 disulfide bond increases the conformational flexibility of the occluding loop, although the conformational stability of the overall structure is little affected. The structural characteristics of the complex elucidated by X-ray analysis were suggested to be also intrinsic and stable in the dynamic state; the hydrogen bonding/electrostatic interactions between the main and side chains of CA074 and the Sn and Sn' subsites of the enzyme were maintained throughout the MD simulation. Furthermore, the simulation made clear that the binding of CA074 significantly restricted the conformational flexibility of the substrate binding region, especially the occluding loop, of cathepsin B. Statistical analyses during the simulation suggest that the selectivity of CA074 for cathepsin B stems from the tight P1'-S1' and P2'-S2' interactions, assisted in particular by double hydrogen bonds between the carboxyl two oxygens of the CA074 C-terminus and the imidazole NH groups of His110 and His111 residues.

Preparation of poly(alkylenebenzimidazole) by ruthenium complex catalyzed polycondensation of 3,3?-diaminobenzidine with ?,?-diols

The reactions of 3,3′-diaminobenzidine with 1,12-dodecanediol in 1 : 1–1:3 molar ratios in the presence of RuCl2(PPh3)3 catalyst give poly(alkylenebenzimidazole), [(CH2)11O(CH2)11Im/(CH2)10Im]n (Im: 5,5′-dibenzimidazole-2,2′-diyl) (Ia-Id) in 71–92% yields. The relative ratio between the [(CH2)11O (CH2)11Im] unit (A) and the [- (CH2)10Im] unit (B) in the polymer chain varies depending on the ratio of the substrates used. The polymer Ia obtained from the 1 : 3 reaction contains these structural units in a 98 : 2 ratio. The polymers are soluble in polar solvents such as DMF (N,N-dimethylformamide), DMSO (dimethyl sulfoxide), and NMP (N-methyl-2-pyrrolidone) and have molecular weights Mn (Mw) of 4,200–4,800 (4,800–6,500) by GPC (polystyrene standard). The polymerization of the diol and 3,3′-diaminobenzidine in higher molar ratios leads to partial cross-linking of the resulting polymers Ie and If via condensation of imidazole NH group with CH2OH group. Similar reactions of 3,3′-diaminobenzidine with α,ω-diols, HO(CH2)mOH (m = 4–10), in a 1 : 3 molar ratio give the polymers containing [(CH2)m−1O(CH2) m−1Im] and [(CH2) m−2Im] units with partial cross-linked structures. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 1383–1392, 1999