Intramolecular Bridges Research Articles

DABCO‐Mediated Self‐Assembly of Zinc Porphyrin–Perylene Bisimide Monodisperse Multichromophoric Nanoparticles

Line up! Fourfold zinc porphyrin functionalized perylene bisimide has afforded well-defined supramolecular particles by intramolecular cofacial bridging of zinc porphyrin units through the ditopic ligand DABCO as revealed by UV/Vis and NMR spectroscopy and AFM studies (see figure).

Synthesis and Catalytic Applications of ansa Compounds with Cycloalkyl Moieties as Bridging Units: A Comparative Study

AbstractThe molybdenum and tungsten compounds (Mo{η5‐C5H4[CH(CH2)n]‐η1‐CH}(CO)3) and (W{η5‐C5H4[CH(CH2)3]‐η1‐CH}(CO)3) (2a, 3a n=3; 2b, 3b n=4; 2c, 3c n=5; 2d, 3d n=6) were synthesized by reacting the spiro‐bicyclic compounds 1a–d with the complex [M(CO)3(tach)] (M=molybdenum, tungsten; tach=1,3,5‐trimethylhexahydro‐1,3,5‐triazine). NMR spectroscopy, as well as X‐ray diffraction studies, confirm the formation of an intramolecular ansa bridge. The complexes display a good stability in the solid state (stable up to 180 °C under air, as determined by thermogravimetric studies) and are highly active catalysts at room temperature (molybdenum compounds) or above (tungsten compounds) in olefin epoxidation. In the case of cyclooctene as substrate, TOFs up to ca. 11800 h−1 are obtained. Moreover, most of the catalysts described here display a high selectivity in the epoxidation of cis‐ and trans‐stilbene. In addition, the novel complexes were compared with previously synthesized related compounds, at least matching their catalytic performances.

Preparation, Facile Deprotonation, and Rapid H/D Exchange of the μ-Hydride Diiron Model Complexes of the [FeFe]-Hydrogenase Containing a Pendant Amine in a Chelating Diphosphine Ligand

The CO-displacement of [(mu-pdt)Fe(2)(CO)(6)] with (Ph(2)PCH(2))(2)N(n-Pr) in refluxing toluene gave an unsymmetrical chelating complex [(mu-pdt){Fe(CO)(3)}{Fe(CO)(kappa(2)-Ph(2)PCH(2)N(n-Pr)CH(2)PPh(2)}] (1) as a major product, together with a small amount of the symmetrical intramolecular bridging complex [(mu-pdt){mu-Ph(2)PCH(2)N(n-Pr)CH(2)PPh(2)}{Fe(CO)(2)}(2)] (2) and the intermolecular bridging complex [{mu,kappa(1),kappa(1)-Ph(2)PCH(2)N(n-Pr)CH(2)PPh(2)}{(mu-pdt)Fe(2)(CO)(5)}(2)] (3). In contrast, the reaction of [(mu-pdt)Fe(2)(CO)(6)] with (Ph(2)PCH(2))(2)NR (R = n-Pr, Ph) afforded the intermolecular bridging isomers 3 and 4 in the presence of a CO-removing reagent Me(3)NO.2H(2)O in CH(3)CN at room temperature. The molecular structures of 1, 3, and 4, as well as the doubly protonated complex [1(H(N)H(mu))](OTf)(2)] were determined by X-ray analyses. The protonation processes of 1 with HBF(4).Et(2)O and HOTf were studied in different solvents. The presence of the H(mu)...H(N) interaction in [1(H(N)H(mu))](2+) was studied by relaxation time T(1) and spin saturation transfer measurements. The mu-hydride of [1(H(mu))](+) and [1(H(N)H(mu))](2+) undergo facile deprotonation with aniline and rapid H/D exchange with deuterons in solution. In contrast, neither deprotonation nor H/D exchange was detected for [(mu-H)(mu-pdt){Fe(CO)(3)}{Fe(CO)(kappa(2)-dppp)}](+) ([5(H(mu))](+), dppp = Ph(2)PCH(2)CH(2)CH(2)PPh(2)) without internal base.

Light chain somatic mutations change thermodynamics of binding and water coordination in the HyHEL-10 family of antibodies

Thermodynamic and structural studies addressed the increased affinity due to L-chain somatic mutations in the HyHEL-10 family of affinity matured IgG antibodies, using ITC, SPR with van’t Hoff analysis, and X-ray crystallography. When compared to the parental antibody H26L26, the H26L10 and H26L8 chimeras binding to lysozyme showed an increase in favorable ΔG° of −1.2±0.1kcalmol−1 and −1.3±0.1kcalmol−1, respectively. Increase in affinity of the H26L10 chimera was due to a net increase in favorable enthalpy change with little difference in change in entropy compared to H26L26. The H26L8 chimera exhibited the greatest increase in favorable enthalpy but also showed an increase in unfavorable entropy change, with the result being that the affinities of both chimeras were essentially equivalent. Site-directed L-chain mutants identified the shared somatic mutation S30G as the dominant contributor to increasing affinity to lysozyme. This mutation was not influenced by H-chain somatic mutations. Residue 30L is at the periphery of the binding interface and S30G effects an increase in hydrophobicity and decrease in H-bonding ability and size, but does not make any new energetically important antigen contacts. A new 1.2-Å structure of the H10L10–HEL complex showed changes in the pattern of both inter- and intra-molecular water bridging with no other significant structural alterations near the binding interface compared to the H26L26–HEL complex. These results highlight the necessity for investigating both the structure and the thermodynamics associated with introduced mutations, in order to better assess and understand their impact on binding. Furthermore, it provides an important example of how backbone flexibility and water-bridging may favorably influence the thermodynamics of an antibody–antigen interaction.

Why is DNA polymorphic while RNA is not?

In DNA, the base-sugar hydrophobic interactions between the 2′-methylene group of the 2′-deoxyribose sugar and the base (H6 in pyrimidines and H8 in purines) on the 3′-side appear to act as a ball joint and facilitate the A-DNA B-DNA conformational interconversion by lowering the pseudorotational barrier. These and other sugar-base interactions coupled with the inherently more flexible 2′-deoxyribofuranose ring allow DNA to occur in a variety of polymorphic helical states. In contrast, the 2′-hydroxyl group in RNA not only sterically disfavors the B-type structure, but the inherently less flexible ribofuranose ring is further stabilized in the A-type structure by intramolecular hydrogen-bonded water bridge between the 2′-OH group and the base (O2 in pyrimidines and N3 in purines). This lack of flexibility of RNA dictates that DNA-RNA hybrid structures assume the A-type helix.

An insight into the thermostability of a pair of xylanases: the role of hydrogen bonds

Xylanases are enzymes that are very tolerant to temperature. Their potential use in several biotechnological applications, such as animal food manufacture and pulp bleaching, is due to their intrinsic thermostability. The present report deals with two xylanases, the mesophilic xylanase from Bacillus circulans, BCX, and the thermophilic xylanase from Thermomyces lanuginosus,TLX. These enzymes belong to family 11, and they are the most structurally similar mesophilic–thermophilic pair. Molecular dynamics simulations were employed to investigate the factors responsible for the different thermostabilities exhibited by these structurally similar enzymes. Their active site is their most rigid region, and it is equally rigid at all temperatures. Inter and intramolecular interactions, hydrogen bonds in particular, are the key to the main differences between BCX and TLX. The intramolecular hydrogen bonds and salt bridges are important for maintenance of the backbone rigidity even at high temperature, and the highly solvated surface is a clear optimization in TLX compared with BCX. The main differences between these two enzymes can be found on the fingers domain, which indicates that this domain must be the target for the site-directed mutagenesis responsible for improving the temperature tolerance of this family of enzymes.

Intramolecular hydrogen bonding in 3‐imino‐propenylamine: Theoretical investigations

AbstractIntramolecular H‐bonds existing for derivatives of 3‐imino‐propenylamine have been studied using the B3LYP/6‐311++G** level of theory. The nature of these interactions, known as resonance‐assisted hydrogen bonds, has been discussed. Vibrational frequencies for α‐derivatives were calculated at the same level of theory. The topological properties of the electron density distributions for NH···N intramolecular bridges have been analyzed in terms of the Bader theory of atoms in molecules (AIM). Calculation for 3‐imino‐propenylamine derivatives in water solution were also carried out at B3LYP/6‐311++G** level of theory. Finally, the analysis of hydrogen bond in this molecule and their derivatives by quantum theory of natural bond orbital methods fairly support the ab initio results. © 2009 Wiley Periodicals, Inc. Int J Quantum Chem, 2009

Intramolecular hydrogen bonding in derivatives of 3‐amino‐propenethial

AbstractIntramolecular H‐bonds existing for derivatives of 3‐amino‐propenethial have been studied using the B3LYP/6‐311++G** level of theory. The nature of these interactions, known as resonance assisted hydrogen bonds, has been discussed. The topological properties of the electron density distributions for N—H—S intramolecular bridges have been analyzed in terms of the Bader theory of atoms in molecules. Correlations between the H‐bond strength and topological parameters have been also studied. Furthermore, we obtained the exact value of the intramolecular hydrogen bond energies by the related rotamers method. © 2009 Wiley Periodicals, Inc. Int J Quantum Chem, 2009

Deprotonation of hydrogen bonded Schiff bases by three strong nitrogen bases

Three Schiff bases obtained from substituted salicylaldehydes and 2-hydroxy-1-naphthaldehyde and aliphatic amines were investigated in terms of possible withdrawal of tautomeric proton from intramolecular hydrogen bridge. Three strong nitrogen bases: 1,8-bis(dimethylamino)naphtalene (DMAN), 1,1,3,3-tetramethylguanidine (TMG) and 1,8-bis(tetramethylguanidino)naphthalene (TMGN) were used as deprotonating agents in acetonitrile solution at room temperature. In the specified conditions it was found that only in the case of 5-nitrosalicylaldehyde and isopropyl amine derivative this process could be performed using TMG and TMGN as a base. The other derivatives, where bridged proton is shifted to oxygen or nitrogen atom, do not undergo such reaction. The deprotonation process was monitored by nitrogen and proton NMR measurements.

Neutral Ruthenium Carbene Complexes bearing N,N,O Heteroscorpionate Ligands: Syntheses and Activity in Metathesis Reactions

Neutral Fischer-type ruthenium(II) aminocarbene complexes bearing the bis(3,5-dimethylpyrazol-1-yl)acetato (bdmpza) ligand have been synthesized by addition of ammonia or methylamine to the α-carbon atom of vinylidene and allenylidene complexes. Reaction with dimethylamine was not successful. These differences in the chemical behavior can be explained by the intermediate formation of intramolecular hydrogen bridges that have been indicated by DFT calculations. Furthermore, octahedral ruthenium(II) benzylidene complexes with the bis(pyrazol-1-yl)acetato (bpza) and the bdmpza ligand were obtained by reacting [RuCl2(═CHPh)(PR3)2] (R = Cy, Ph) with K[bpza] or K[bdmpza], respectively. The latter complexes have successfully been tested for RCM reactions.

Oligomerization of hantaviral nucleocapsid protein: charged residues in the N-terminal coiled-coil domain contribute to intermolecular interactions

The nucleocapsid (N) protein of hantaviruses (family Bunyaviridae) is the most abundant component of the virion; it encapsidates genomic RNA segments and participates in viral genome transcription and replication, as well as in virus assembly. During RNA encapsidation, the N protein forms intermediate trimers and then oligomers via 'head-to-head, tail-to-tail' interactions. In previous work, using Tula hantavirus (TULV) N protein as a model, it was demonstrated that an intact coiled-coil structure of the N terminus is crucial for the oligomerization capacity of the N protein and that the hydrophobic 'a' residues from the second alpha-helix are especially important. Here, the importance of charged amino acid residues located within the coiled-coil for trimer formation and oligomerization was analysed. To predict the interacting surfaces of the monomers, the previous in silico model of TULV coiled-coils was first upgraded, taking advantage of the recently published crystal structure of the N-terminal coiled-coil of the Sin Nombre virus N protein. The results obtained using a mammalian two-hybrid assay suggested that conserved, charged amino acid residues within the coiled-coil make a substantial contribution to N protein oligomerization. This contribution probably involves (i) the formation of interacting surfaces of the N monomers (residues D35 and D38, located at the tip of the coiled-coil loop, and R63 appear particularly important) and (ii) stabilization of the coiled-coil via intramolecular ionic bridging (with E55 as a key player). It is hypothesized that the tips of the coiled-coils are the first to come into direct contact and thus to initiate tight packing of the three structures.

Morphology, toughness mechanism, and thermal properties of hyperbranched epoxy modified diglycidyl ether of bisphenol A (DGEBA) interpenetrating polymer networks

AbstractNew hyperbranched poly(trimellitic anhydride‐triethylene glycol) ester epoxy (HTTE) is synthesized and used to toughen diglycidyl ether of bisphenol A (DGEBA) 4,4′‐diaminodiphenylmethane (DDM) resin system. The effects of content and generation number of HTTE on the performance of the cured systems are studied in detail. The impact strength is improved 2–7 times for HTTE/DGEBA blends compared with that of the unmodified system. Scanning electron microscopy (SEM) of fracture surface shows cavitations at center and fibrous yielding phenomenon at edge which indicated that the particle cavitations, shear yield deformation, and in situ toughness mechanism are the main toughening mechanisms. The dynamic mechanical thermal analyzer (DMA) analyses suggest that phase separation occurred as interpenetrating polymer networks (IPNs) for the HTTE/DGEBA amine systems. The IPN maintains transparency and shows higher modulus than the neat epoxy. The glass transition temperature (Tg) decreases to some extent compared with the neat epoxy. The Tg increases with increase in the generation number from first to third of HTTE and the concentrations of hard segment. The HTTE leads to a small decrease in thermal stability with the increasing content from TGA analysis. The thermal stability increases with increase in the generation number from first to third. Moreover, HTTE promotes char formation in the HTTE/DGEBA blends. The increase in thermal properties from first to third generation number is attributed to the increase in the molar mass and intramolecular hydrogen bridges, the increasing interaction of the HTTE/DGEBA IPNs, and the increasing crosslinking density due to the availability of a greater number of end hydroxyl and end epoxide functions. Copyright © 2008 John Wiley & Sons, Ltd.

The crystal structure of halofantrine–ferriprotoporphyrin IX and the mechanism of action of arylmethanol antimalarials

The crystal structure of the complex formed between the antimalarial drug halofantrine and ferriprotoporphyrin IX (Fe(III)PPIX) has been determined by single crystal X-ray diffraction. The structure shows that halofantrine coordinates to the Fe(III) center through its alcohol functionality in addition to π-stacking of the phenanthrene ring over the porphyrin. The length of the Fe(III)–O bond is consistent with an alkoxide and not an alcohol coordinating group. The iron porphyrin is five coordinate and monomeric. Changes in the electronic spectrum of Fe(III)PPIX upon addition of halofantrine base in acetonitrile solution are almost identical to those observed upon addition of quinidine free base in the same solvent. This suggests homologous binding. Molecular mechanics modeling of Fe(III)PPIX complexes of quinidine, quinine, 9-epiquinine and 9-epiquinidine based on this homology suggests that the antimalarially active quinidine and quinine can readily adopt conformations that permit formation of an intramolecular salt bridge between the protonated quinuclidine tertiary amino group and unprotonated heme propionate group, while the inactive epimers 9-epiquinidine and 9-epiquinine have to adopt high energy conformations in order to accommodate such salt bridge formation. We propose that salt bridge formation may interrupt formation of the hemozoin precursor dimer formed during the heme detoxification pathway and so account for the strong activity of the two active isomers.

Photo-control of peptide conformation on a timescale of seconds with a conformationally constrained, blue-absorbing, photo-switchable linker

Azobenzene derivatives can be used to reversibly photo-regulate conformation and activity when introduced as intramolecular bridges in peptides and proteins. Here we report the design, synthesis, and characterization of an azobenzene derivative that absorbs between 400-450 nm in aqueous solution to produce the cis isomer, and relaxes back to the trans isomer with a half-life of a few seconds at room temperature. In the trans form, the linker can span a distance of approximately 25 A, so that it can bridge Cys residues spaced i, i + 15 in an alpha-helix. Switching of the azobenzene cross-linker from trans to cis causes a decrease in the helix content of peptides where the linker is attached via Cys residues spaced at i, i + 15 and i, i + 14 positions, no change in helix content with Cys residues spaced i, i + 11 and an increase in helix content in a peptide with Cys residues spaced at i, i + 7. In the presence of 10 mM reduced glutathione, the azobenzene cross-linker continued to photo-switch after 24 hours. This cross-linker design thus expands the possibilities for fast photo-control of peptide and protein structure in biochemical systems.

Determining the Structure and Mode of Action of Microbisporicin, a Potent Lantibiotic Active Against Multiresistant Pathogens

Antibiotics blocking bacterial cell wall assembly (beta-lactams and glycopeptides) are facing a challenge from the progressive spread of resistant pathogens. Lantibiotics are promising candidates to alleviate this problem. Microbisporicin, the most potent antibacterial among known comparable lantibiotics, was discovered during a screening applied to uncommon actinomycetes. It is produced by Microbispora sp. as two similarly active and structurally related polypeptides (A1, 2246-Da and A2, 2230-Da) of 24 amino acids linked by 5 intramolecular thioether bridges. Microbisporicin contains two posttranslational modifications that have never been reported previously in lantibiotics: 5-chloro-trypthopan and mono- (in A2) or bis-hydroxylated (in A1) proline. Consistent with screening criteria, microbisporicin selectively blocks peptidoglycan biosynthesis, causing cytoplasmic UDP-linked precursor accumulation. Considering its spectrum of activity and its efficacy in vivo, microbisporicin represents a promising antibiotic to treat emerging infections.

Regioselective intramolecular bridging of p-tert-butylcalix[10]arene

The synthesis and characterization of a series of regioselective intramolecular bridging of calix[10]arene are described for the first time. Reacting p-tert-butylcalix[10]arene with tri-ethylene glycol ditosylate using K2CO3 as a base in toluene, 1,2-calix[10]crown-4 2a, 1,4-calix[10]crown-4 2b and 1,6-calix[10]crown-4 2c were obtained in yields of 9%, 14% and 7%, respectively. While using Cs2CO3/acetone instead of K2CO3/toluene, the 1,4-calix[10]crown-4 2b was obtained selectively in good yield up to 50%.

Open Platinum Aggregate Frameworks with Overhead Dithiolate Bridges

AbstractA convenient method has been developed to bring together two discrete moieties of [Pt2(μ‐S)2(PPh3)4] to give an open Pt4 aggregate of Pt2···(spacer)···Pt2, as exemplified in the isolation of [(PPh3)4Pt2(μ‐S)(μ‐SRS)(μ‐S)Pt2(PPh3)4](PF6)2 [R = m‐CH2C6H4CH2, p‐CH2C6H4CH2, CH2C10H6CH2, and CH2(C6H4)2CH2]. The spacer is a dithiolate with an extended skeletal backbone formed from the alkylation of sulfide with a suitable dibromo‐organic compound. This synthetic methodology can tolerate a range of conformationally contrasting thiolate substituents with different chemical functionalities. Shorter or stereochemically more restrictive spacers could opt to be an intramolecular bridge over the Pt2 core, as given in [Pt2(μ‐S‐o‐CH2C6H4‐C6H4CH2S)(PPh3)4](PF6)2. A few representative complexes have been characterized by single‐crystal X‐ray diffraction analysis.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

The Synthesis, Characterization, Spectroscopic Studies and Catalyst Properties of Some New Dinuclear Uranyl (VI) Metal Complexes Bearing Different vic‐Dioxime Groups

The synthesis, characterization and spectroscopic studies of some new dinuclear uranyl (VI) metal complexes prepared from different vic‐dioximes ligands and the uranyl acetate metal salt. The structure of these uranyl (VI) metal complexes have been determined as according to elemental analysis, 1H‐NMR spectra, FT‐IR spectra, UV‐Vis spectra, magnetic susceptibility measurements, melting point and molar conductivity measurements. The metal to ligand ratios of the homodinuclear or heterodinuclear (VI) complexes were found to be 2:2, through N and O‐cordinating. The intramolecular hydrogen bridging O‐H…O protons have not been observed in all uranyl (VI) metal complexes. UO2 (VI) metal complexes are non‐electrolytes as shown by their molar conductivities (ΛM) in DMF (dimethyl formamide) at 10−3 M. All dinuclear uranyl metal complexes are soluble in common organic solvents (such as DMF and DMSO). Both compounds exhibit nearly identical X‐ray powder patterns for [(L1H2)2(UO2)2(OH)2] (1) and [(L6H2)2(UO2)2(OH)2] (6). Also, we are use uranyl (VI) complexes as catalyst in the hydrolysis of NaBH4 liberating hydrogen gas.

Probing the Intramolecular Hydrogen Bond of 2-(2-Hydroxyphenyl)benzotriazoles in Polar Environment: A Photophysical Study of UV Absorber Efficiency

An in-depth photophysical study is presented for a series of 2-(2-hydroxyphenyl)benzotriazoles (HBzTs); the structural characteristic of all these photostabilizers is their strong intramolecular hydrogen bridge (IMHB). Tinuvin P (TIN P, 11a) and six other HBzTs, with no substituent in the 3'-position ortho to the hydroxy function, show pronounced phosphorescence already in the dark (at 77 K in a polar glass). Upon irradiation, the phosphorescence intensity rises further until an equilibrium value is attained (up to 1.5 fold the dark value). A kinetic model is given which excellently reproduces this phosphorescence evolution: it demonstrates phosphorescence to arise from open conformers where the IMHB has been broken. Phosphorescence excitation spectra match the absorption spectra of the open conformer and also that of the O-methyl homologue 11A which cannot form an IMHB. Fluorescence spectra likewise prove the equilibrium between the closed and open conformer for these HBzTs. In unpolar glasses as well as in the crystalline state, TIN P displays a long-wavelength (red) fluorescence (with an enormous Stokes shift of approximately 10.000 cm-1) which is associated with the excited singlet state of the closed form after proton transfer within the IMHB, S1'(C). In polar matrixes, on the other hand, a blue fluorescence is observed (with a regular Stokes shift) for all those HBzTs which have no 3'-substituent shielding the IMHB against being opened by the polar solvent. This blue fluorescence, just as the characteristic phosphorescence evolution for these compounds, is associated with the open conformer. For HBzTs with an (alkyl) group ortho to the bridging OH group, however, a long-wavelength (red) fluorescence is again observed. The shielding effect of the 3'-substituent shows a fine gradation, cumyl >/= 1,1,3,3-tetramethylbutyl (isooctyl) > t-butyl >/= methyl.

Studies of Arginine–Arene Interactions through Synthesis and Evaluation of a Series of Galectin‐Binding Aromatic Lactose Esters

Aromatic lactose 2-O-esters were synthesized and used to probe arene-arginine interactions with the galectin family of proteins. They were found to be low microM inhibitors of galectin-1, -3, and -9N-terminal domain and moderate inhibitors of galectin-7, but not inhibitors of galectin-8N-terminal, which lacks an arginine residue close to the critical, esterified lactose 2-O-position. Molecular modeling of galectins in complex with aromatic lactose 2-O-esters, as well as binding studies with a galectin-3 R186S mutant, confirmed that the inhibitory efficiency of the lactose 2-O-esters was due to the formation of strong interactions between the aromatic ester moieties and the arginine guanidinium groups of galectin-1 and -3. An important common feature shared by galectin-1 and -3 was that the arginines formed in-plane ion pairs with two side-chain carboxylates, which resulted in extended planar pi-electron surfaces that did not require solvation by water; these surfaces were ideal for stacking with aromatic moieties of the ligands. The results provide a basis for the design of lectin inhibitors and drugs that exploit interactions with arginine side-chains via aromatic moieties, which are involved in intramolecular protein salt bridges.