Hydrogen Binding Interactions Research Articles

Molecular recognition: minimizing the acid–base interaction of a tunable host–guest system changes the selectivity of binding

Two new receptors incorporating a 4-n-butyl aniline moiety has been designed, synthesized and evaluated for their binding properties towards a series of ureido-glycine derivatives. The host design is based on an urea adamantyl host motif known from large generations of poly(propylene imine) dendrimers functionalized with urea adamantyl moieties on the periphery. The design of the host molecules was directed towards a study of the effects of basicity of an amine function versus the effect of molecular recognition on the binding strength as seen from comparing the results obtained in the present work with previously guest–host studies. The guest–host interaction features an electrostatic interaction and multiple hydrogen binding interactions, where the main difference between the hosts described here and previously described is a substitution from an amine to aniline. Anilines are weaker bases than aliphatic amines and they generally give lower binding constants when treated with acidic guest molecules. The association constants have been measured using NMR titrations and the nature of the guest–host system is discussed based on these results. A general decrease in binding affinities is observed upon changing from the trialkyl amine hosts to the dialkyl aniline based hosts. One exception was observed where the weaker base host had stronger affinity to one of the guests. Thus, when the basicity of the host is decreased other factors influence the binding such as a better geometric fit. A crystal structure of one of the receptors has been solved and it shows no intramolecular hydrogen bonding.

Novel N,N′‐Diacylhydrazine‐Based Colorimetric Receptors for Selective Sensing of Fluoride and Acetate Anions

AbstractThree novel and simple N,N′‐diacylhydrazine‐based colorimetric receptors have been prepared. The binding properties of the receptors to anions such as F−, Cl−, Br−, AcO−, HSO4− and H2PO4− in acetonitrile solution were examined by UV‐Vis spectroscopy methods, which show high sensitivity and selectivity to F− and AcO− over other anions. The results indicated that a 1:1 stoichiometry complex was formed between the receptors and the anions, while 1H NMR titrations confirmed hydrogen binding interaction between the receptors and the anions.

Recruitment of Both Uniform and Differential Binding Energy in Enzymatic Catalysis: Xylanases from Families 10 and 11

The contributions of enzyme-substrate hydrogen-binding interactions to catalysis by two different families of xylanases were evaluated through kinetic studies with two representative wild-type enzymes, Cellulomonas fimi xylanase (Cex) and Bacillus circulans xylanase (Bcx), on a series of monodeoxygenated and monodeoxyfluorinated p-nitrophenyl xylobioside substrates. Effects of substitution in the distal (-2 subsite) sugar on kcat/Km for Cex were moderately large (up to 2.9 kcal mol-1), with no effect seen on kcat. By contrast, substantial effects upon both kcat and kcat/Km were seen for substrates modified in the proximal (-1 subsite) sugar. Very similar results were obtained with Bcx. Kinetic analyses with a series of eight mutants of Cex in which active site residues interacting with the substrate were mutated yielded complementary insights. Again, interactions with the distal (-2) sugar were seen to contribute substantially to kcat/Km (up to 3.7 kcal mol-1), thus to the formation of the glycosyl-enzyme intermediate, but not to kcat, thus to the hydrolysis of the glycosyl-enzyme. Interactions with the proximal (-1) sugar are much more significant, contributing up to 6.7 kcal mol-1 to both kcat/Km and kcat. These results together indicate that interactions with the distal sugar maintain similar magnitudes in the transition states for glycosylation and deglycosylation as well as in the glycosyl-enzyme intermediate and can be referred to as "uniform binding interactions" in the parlance of Albery and Knowles (Albery, W. J., and Knowles, J. R. (1976) Biochemistry 15, 5631-5640). Interactions with the proximal sugar are considerably stronger at the deglycosylation transition state than in the intermediate, and fall into the category of differential binding interactions. This behavior likely has its origins in the changes in ring conformation of the proximal sugar but not of the distal sugar between the ground state and the reaction transition state. Correlation of these individual interaction energies with the hydrogen-bonding pattern seen in the glycosyl-enzyme intermediate allows for the assignment of hydrogen-bond strengths to each interaction, with good correlation between the two approaches. These findings are relevant to the discussion of remote binding effects upon enzymatic catalysis.

The role of vacancies in the hydrogen storage properties of Prussian blue analogues

The porosity and hydrogen storage properties of the dehydrated Prussian blue type solids Ga[Co(CN) 6], Fe 4[Fe(CN) 6] 3, M 2[Fe(CN) 6] (M = Mn, Co, Ni, Cu), and Co 3[Co(CN) 5] 2 are reported and compared to those of M 3[Co(CN) 6] 2 (M = Mn, Fe, Co, Ni, Cu, Zn). Nitrogen sorption measurements suggest partial framework collapse for M 2[Fe(CN) 6] (M = Co, Ni) and Co 3[Co(CN) 5] 2, and complete collapse for Mn 2[Fe(CN) 6]. Hydrogen sorption isotherms measured at 77 K reveal a correlation between uptake capacity and the concentration of framework vacancies, with Langmuir–Freundlich fits predicting saturation values of 1.4 wt.% for Ga[Co(CN) 6], 1.6 wt.% for Fe 4[Fe(CN) 6] 3, 2.1 wt.% for Cu 3[Co(CN) 6] 2, and 2.3 wt.% for Cu 2[Fe(CN) 6]. Enthalpies of H 2 adsorption were calculated from isotherms measured at 77 and 87 K. Importantly, the values obtained for compounds with framework vacancies are not significantly greater than for the fully-occupied framework of Ga[Co(CN) 6] (6.3–6.9 kJ/mol). This suggests that the exposed metal coordination sites in these materials do not dominate the hydrogen binding interaction.

Synthesis, characterization and in vitro biological activity studies of Cu–M (M = Cu 2+, Co 2+, Ni 2+, Mn 2+, Zn 2+) bimetallic complexes

Six new bimetallic complexes of the type CuCu, CuCo, CuNi, CuZn and CuMn were prepared. The structures of these complexes and the ligand have been proposed on the basis of FAB mass, elemental analysis, UV–vis, IR, EPR and CV studies. All the complexes completely cleave pBS (SK−) DNA at a concentration of 10 μM; however, even at lower concentrations of 2 μM and 0.1 μM, the complexes ( I and Ia) showed partial cleavage. The results of the fluorescence binding studies of the metal complexes with CT-DNA showed that the presence of aliphatic ligands added additional binding effects including electrostatic, hydrogen binding and vander Waals interactions. Complexes ( I, Ia) showed 50% inhibition of COX-1 and COX-2 activities at as low a concentration as 12.5 μM, 13.5 μM, 14 μM and 14.5 μM. Inhibition assay of top I and top II by different complexes in mutant yeast strains (JN394, JN394 t −1 and JN394 t 2–5) with all the complexes showed significant inhibition of topoisomerase at 5 μM concentration. Complexes I and Ia exhibited good anti-microbial activities against all human pathogens tested except Klebsiella pneumoniae. The following studies showed that among the synthesized bimetallic complexes, complexes I and Ia seem to be promising candidates possessing DNA cleavage activities besides anti-microbial and anti-inflammatory properties to serve as chemical nucleases and chemotherapeutic agents.

A Weak Fe–O Bond in the Oxygenated Complex of the Nitric-oxide Synthase of Staphylococcus aureus

Little is known about the intermediates formed during catalysis by nitric-oxide synthase (NOS). We report here the characterization by resonance Raman spectroscopy of the oxygenated complex of the NOS from Staphylococcus aureus (saNOS) as well as the kinetics of formation and decay of the complex. An oxygenated complex transiently formed after mixing reduced saNOS with oxygen and decayed to the ferric enzyme with kinetics that were dependent on the substrate L-arginine and the cofactor H(4)B. The oxygenated complex displayed a Soret absorption band centered at 430 nm. Resonance Raman spectroscopy revealed that it can be described as a ferric superoxide form (Fe(III)O(2)(-)) with a single nu(O-O) mode at 1135 cm(-1). In the presence of L-arginine, an additional nu(O-O) mode at 1123 cm(-1) was observed, indicating an increased pi back-bonding electron donation to the bound oxygen induced by the substrate. With saNOS, this is the first time that the nu(Fe-O) mode of a NOS has been observed. The low frequency of this mode, at 517 cm(-1), points to an oxygenated complex that differs from that of P450(cam). The electronic structure of the oxygenated complex and the effect of L-arginine are discussed in relation to the kinetic properties of saNOS and other NOS.

DFT computational studies on rotation barriers, tautomerism, intramolecular hydrogen bond, and solvent effects in 8‐hydroxyquinoline

AbstractIntramolecular hydrogen binding interactions in 8‐hydroxyquinoline, both in its zwitterionic tautomer and in the rotamer without the intramolecular hydrogen bond (IHB), have been computed using the B3LYP and MPW1K density functionals. The rotation of the OH bond and intramolecular proton transfer reactions were studied theoretically. The following theory levels have been applied: B3LYP/6‐31G(d,p), B3LYP/6‐311++G(d,p), MPW1K/6‐311++G(d,p), and MPW1K/6‐311++G(2d,3p)//MPW1K/6‐311++G(d,p). Natural bond orbital (NBO) analysis has also been carried out. The effect of medium (benzene, chloroform, tetrahydrofuran, 1,2‐dichloroethane, acetone, water) was simulated using the self‐consistent reaction field (SCRF) method within the framework of the polarizable continuum model (PCM), at the MPW1K/6‐311++G(d,p) level. The evolution of geometry, relative energies, heights of rotation (around the OH bond) and tautomerization barriers, IHB energies, and ΔG(solv) have been systematically investigated. The results obtained have shown the failure to neglect some changes of the above characteristics in polar media with respect to the gaseous phase. The series of stability of the forms under study in the gaseous phase remains the same in solution. Thus, in spite of the important role of the solvent electrostatic effects, the intrinsic stability of those species overcomes the solvent effects. © 2005 Wiley Periodicals, Inc. Int J Quantum Chem, 2006

Structural Properties of Benzimidazole Cavitand and Its Selective Recognition toward 4-Methylbenzamide over 4-Methylanilide

The conformations and properties of cavitand 5 with four benzimidazole flaps are studied by (1)H NMR. The benzimidazole cavitand 5 can form very stable vase structures with an enforced concave cavity by intermolecular hydrogen bonding with four hydroxyl-containing molecules, X-OH, such as methanol (X = Me), acetic acid (X = CH(3)CO), and trifluoroacetic acid (X = CF(3)CO). The stronger hydrogen bond donor strengths of X-OH are, the stronger hydrogen bonds are formed between the NH and N atoms of the neighboring benzimidazole fragments and the more vase structures of 5.4HOX are stable. The annular tautomerism of 5 in CDCl(3)/CD(3)OD (9:1, v/v) due to the proton exchange between NH and N atoms of the neighboring benzimidazole fragments is observed by 400 MHz (1)H NMR, and the free energy of activation is measured as DeltaG++(210) = 10.2 kcal/mol at a coalescence temperature of 210 K. Cavitand 5 forms inclusion complexes with 4-methylbezamide guests such as 4-methyl-N-p-tolylbenzamide 6 and N,4-dimethylbenzamide 7 in water-saturated CDCl(3). However, an isomorphic 4-methylanilide guest such as N-4-tolylacetamide 8 cannot be recognized in the concave cavity of 5. This high selectivity toward 4-methylbenzamide over 4-methylanilide seems attributable to the hydrogen-binding interaction between the NH proton of 4-methylbezamide guest 7 and the oxygen atom of the closest water molecule.

Surface modified microfiltration membranes with molecularly recognising properties

Polyvinilidene fluoride (PVDF-phob and PVDF-phil) and polyethersulfone (PES) microfiltration membranes were surface modified with a thin layer of molecular imprinted polymer (MIP). This material is selective to adenosine 3:5-cyclic monophosphate (cAMP) via photoinitiated copolymerisation of 2-(dimethylamino)ethyl methacrylate as a functional monomer and trimethylopropane trimethacrylate as a cross-linker in the presence of cAMP in ethanol/water solutions. The specific and non-specific template binding of MIP during filtration of aqueous solutions of cAMP was studied for membranes with different degrees of modification. It was concluded that the ability of MIP membranes to bind cAMP is a result of both the specific size and shape of recognising sites in addition to the correct position of the functional groups involved in the template binding through ionic and hydrogen binding interactions. Profile imaging atomic force microscopy and scanning electron microscopy were used to visualise surfaces and cross-sections of MIP membranes. The main advantages of this approach for MIP membrane preparation are very fast MIP layer synthesis and the possibility to obtain MIP composite membranes by controlled deposition on different kind of polymeric supports. Atomic force microscopy in conjunction with the coated colloid probe technique has been used to measure interactions between a silica sphere coated with imprinted polymer and porous supports.

Alginate-konjac glucomannan-chitosan beads as controlled release matrix.

Controlled release beads were prepared by using alginate (ALG), konjac glucomannan (KGM) and chitosan (CHI). Bovine serum albumin and insulin were used as model proteins for in vitro assessments. It was observed that KGM could be contained within beads, and faintness hydrogen binding and electrostatic interaction exist between ALG and KGM by infrared spectra. Clear dents were found on the surface of beads using KGM by scanning electron microscopy. Use of KGM could help increase the payload of drug. After beads were treated by 0.1 N HCl for 4 h and put into pH 7.4 buffers, protein was released from ALG-CHI beads within 1 h, while it was lost from ALG-KGM-CHI beads for 3 h. However, the leaking of protein from ALG-KGM-CHI beads was also increased in 0.1 N HCl solution. Concentration of gelling ion had great effect on release rate and gel structure. Studies of water of hydration had shown that swelling of ALG-KGM-CHI beads was higher than that of ALG-CHI beads in acidic solution, but the opposite result was obtained in alkali solution. The result indicated that the diffusion of protein was related to the viscosity and swelling properties of KGM.

Synthesis, crystal structure and properties of di-μ2-alkoxo bridged binuclear manganese(III) Schiff base complexes

Preparation and isolation of the dimeric manganese(III) complex, [Mn2(Salpa)2(H2O)2Cl2] · 2DMF, (1), was accomplished by air oxidation of a solution containing MnCl2 · 4H2O, Et3N and H2Salpa** in DMF. Complex (2), [Mn2(Salpa)2(H2O)2(N3)2] · 2EtOH was obtained by reacting (1) or [Mn2(Salpa)2(AcO)2], (3), with NaN3 in EtOH. The crystal structure of (1) was determined by X-ray crystallography. It consists of discrete six-coordinate dimeric manganese molecules with unsupported alkoxido bridges, a rare example of a chloride- and water-containing manganese model complex for the oxygen-evolution center of photosystem II. The Mn–O and Mn–N distances are in good agreement with those found for other manganese(III) Schiff base complexes. The Mn–Cl and Mn–O(water) distances of 2.5577(11) and 2.323(3) A, respectively are due to Jahn-Teller distortion at the d4 metal center. The Mn ⋯ Mn distance is 3.0077(12) A. In the crystal, the distance between the H2O molecule and the O atom of DMF of 2.692(5) A suggests hydrogen binding interactions. A t.g. study of (1) confirmed that the complex contains DMF molecules. Magnetic measurements on (1) and (2) reveal the presence of antiferromagnetic spin-exchange interactions between the manganese(III) ions.

New frontiers in host-guest chemistry: The gas phase

Abstract

The receptor-binding site of human relaxin II. A dual prong-binding mechanism

Recent structure/function studies on human relaxin II have led to the conclusion that the arginines B13 and/or B17 are important for biological activity. These studies have been confirmed and extended with the help of chemically synthesized derivatives, i.e. dicitrulline (B13, B17), two monocitrulline (B13 and B17), a dilysine (B13, 17), and alanine (B17) relaxins. The CD spectra of synthetic human relaxin and of the derivatives are indistinguishable. Yet, only the native human relaxin II is biologically active and binds strongly to relaxin receptor preparations in vitro. The inactivation is strictly due to side chain functions, in particular the replacement of either or both arginines in the positions B13 or B17. Binding is mediated by a two-prong electrostatic and hydrogen-binding interaction via arginines B13 and B17. Neither B13 nor B17 alone are sufficient and a positive charge equidistant from the B chain helix is equally insufficient. This binding mechanism appears to be unique, as concerns hormone receptor interaction.

Scanning tunneling microscopy studies of the synthetic polypeptide poly(.gamma.-benzyl L-glutamate)

This paper discusses how STM studies of PBLG in the form of a thin liquid crystalline film cast from dilute DMF onto HOPG reveal a helical molecular structure and a highly organized nature due to strong bipolymer hydrogen-binding interactions. Direct correlation of these images with 3-D x-ray diffraction images is performed and future implications for this data discussed. 13 refs., 6 figs.

Evaluation of intrinsic binding energy from a hydrogen bonding group in an enzyme inhibitor.

This and two accompanying reports describe the intrinsic binding energy derived from a single hydrogen bond between an inhibitor and an enzyme. The results were obtained by comparing matched pairs of inhibitors of the zinc endopeptidase thermolysin that bind to the enzyme in an essentially identical manner but differ in the presence or absence of a specific hydrogen bond. This report describes five phosphorus-containing analogs of the peptides carbobenzoxy-Gly-Leu-X, in which the Gly-Leu peptide linkage is replaced with a phosphonate ester (-PO2(-)-O-). Values for the inhibition constants of these inhibitors show a direct relation with those of the corresponding phosphonamidate analogs (-PO2(-)-NH- in place of the Gly-Leu peptide moiety), which have been characterized previously as transition state analogs. However, each phosphonate ester is bound about 840 times more weakly than the analogous phosphonamidate, reflecting the loss of 4.0 +/- 0.1 kilocalories per mole in binding energy. From these results and the crystallographic analysis in the next report, it can be inferred that the value of 4.0 kilocalories per mole represents the intrinsic binding energy arising from a highly specific hydrogen binding interaction.