Sequence-specific association in aqueous media by integrating hydrogen bonding and dynamic covalent interactions

Oligoamide strands that associate in a sequence-specific fashion into hydrogen-bonded duplexes in nonpolar solvents were converted into disulfide cross-linked duplexes in aqueous media. Thus, by incorporating trityl-protected thiol groups, which allows the reversible formation of disulfide bonds, into the oligoamide strands, only duplexes consisting of complementary hydrogen-bonding sequences were formed in aqueous solution as well as in methanol. The sequence-specific cross-linking of oligoamide strands was confirmed by MALDI-TOF, reverse-phase HPLC, and by isolating a cross-linked duplex. This study demonstrates that the sequence-specificity characteristic of multiply hydrogen-bonded systems can be extended into competitive media through the interplay of H-bonding and reversible covalent interactions, based on which a new class of molecular associating and ligating units that are compatible with both polar and nonpolar environments can be conveniently obtained.     

Interplay of olefin metathesis and multiple hydrogen bonding interactions: covalently cross-linked zippers

Hydrogen-bonded zippers bearing terminal alkene groups were treated with Grubbs' catalyst, leading to covalently cross-linked zippers without violating H-bonding sequence specificity. The yield of a cross-linked zipper depended on the stability of its H-bonded precursor, with a weakly associating pair giving reasonable yields only at high concentrations while strongly associating pairs showed nearly quantitative yields. The integration of thermodynamic (H-bonding) and kinetic (irreversible C═C bond formation) processes suggests the possibility of developing many different covalent association units for constructing molecular structures based on a self-assembling way.     

Helical aromatic oligoamides: reliable, readily predictable folding from the combination of rigidified structural motifs

Factors responsible for the folding of aromatic oligoamides with backbones rigidified by local three-center H-bonds were investigated. The stability of the three-center H-bonds was quantified by the half-lives of amide proton-deuterium exchange reactions, which show that the three-center H-bonds were largely intact at room temperature in the oligomer examined. This result is consistent with our current and previous 2D NMR studies. The overall helical conformation of nonamer 1 was found by variable-temperature NOESY studies to be dynamic. As temperature rose, the end-to-end NOEs rapidly disappeared, while the amide side chain NOEs were still readily detectable, corresponding to the "breath" and stretching of the helix by slightly twisting the local H-bonded rings. Based on the simple repetition of the same structural motif and local conformational preference, undecamer 2 was found to fold into well-defined helical conformation. The predictability of the folding of these backbone-rigidified aromatic oligoamides was demonstrated by a simple modeling method using structural parameters from oligomers with known crystal structures. The reliability and generality of the modeling methods were shown by the excellent agreement between the modeled structures corresponding to 1 and 2 and data from NOESY studies.     

Sequence specificity of hydrogen-bonded molecular duplexes

Hydrogen-bonded molecular duplexes, 1.3 and 1.4, each of which contains a mismatched binding site (acceptor-to-acceptor in 1.3, and donor-to-donor in 1.4), were designed and synthesized based on duplex 1.2. One- and two-dimensional NMR studies demonstrated that, despite their single mismatched binding sites, the backbones of duplexes 1.3 and 1.4 still stayed in register through the formation of the remaining five H-bonds. The backbones of 1.3 and 1.4 adjusted to the presence of the mismatched binding sites by slightly twisting around these sites, which alleviate any head-on repulsive interactions between two H-bond donors (amide O) or between two acceptors (amide H). After 1 equiv of single strand 2, which forms a perfectly matched duplex 1.2 with single strand 1, was added into the solution of either 1.3 or 1.4, only 1.2 and single strand 3 or 4, were detected. Isothermal titration calorimetry (ITC, in chloroform containing 5% DMSO) indicated that duplexes 1.3 and 1.4 were significantly (>40 times) less stable than the corresponding perfectly hydrogen-bonded duplex 1.2. These NMR and ITC results indicate that the pairing of two complementary single strands is not affected by another very similar single strand that contains only one wrong H-bond donor or acceptor, which demonstrates that the self-assembly of this class of H-bonded duplexes is a highly sequence-specific process. The role of these H-bonded duplexes as predictable and programmable molecular recognition units for directing intermolecular interactions has thus been established.     

What can you learn from a molecular probe? New insights on the behavior of C343 in homogeneous solutions and AOT reverse micelles

The behavior of C343, a common molecular probe utilized in solvation dynamics experiments, was studied in homogeneous media and in aqueous and nonaqueous reverse micelles (RMs). In homogeneous media, the Kamlet and Taft solvatochromic comparison method quantified solute-solvent interactions from the absorption and emission bands showing that the solvatochromic behavior of the dye depends not only on the polarity of the medium but also on the hydrogen-bonding properties of the solvent. Specifically, in the ground state the molecule displays a bathochromic shift with the polarity polarizability (pi) and the H-bond acceptor (beta) ability of the solvents and a hypsochromic shift with the hydrogen donor ability (alpha) of the media. The carboxylic acid group causes C343 to display greater sensitivity to the beta than to the pi polarity parameter; this sensitivity increases in the excited state, while the dependence on alpha vanishes. This demonstrates that C343 forms a stable H-bond complex with solvents with high H-bond acceptor ability (high beta) and low H-bond donor character (low alpha). Spectroscopy in nonpolar solvents reveals J-aggregate formation. With information from the Kamlet-Taft analysis, C343 was used to explore RMs composed of water or polar solvents/sodium 1,4-bis-2-ethylhexylsulfosuccinate (AOT)/isooctane using absorption, emission, and time-resolved spectroscopies. Sequestered polar solvents included ethylene glycol (EG), formamide (FA), N,N-dimethylformamide (DMF), and N,N-dimethylacetamide (DMA). Dissolved in the AOT RM systems at low concentration, C343 exists as a monomer, and when introduced to the RM samples in its protonated form, C343 remains protonated driving it to reside in the interface rather than the water pool. The solvathochromic behavior of the dye depends the specific polar solvent encapsulated in the RMs, revealing different types of interactions between the solvents and the surfactant. EG and water H-bond with the AOT sulfonate group destroying their bulk H-bonded structures. While water remains well segregated from the nonpolar regions, EG appears to penetrate into the oil side of the interface. In aqueous AOT RMs, C343 interacts with neither the sulfonate group nor the water, perhaps because of intramolecular H-bonding in the dye. DMF and DMA interact primarily through dipole-dipole forces, and the strong interactions with AOT sodium counterions destroy their bulk structure. FA also interacts with the Na+ counterions but retains its H-bond network present in bulk solvent. Surprisingly, FA appears to be the only polar solvent other than water forming a "polar-solvent pool" with macroscopic properties similar to the bulk.     

Effect of solvent upon CH...O hydrogen bonds with implications for protein folding

The series of CH...O bonds formed between CF(n)H(4-n) (n = 0-3) and water are studied by quantum calculations under vacuum and in various solvents, including aqueous environment. The results are compared with the OH...O bond of the water dimer in the same solvents. Increasing polarity of the solvent leads in all cases to a lessening of the H-bond interaction energy, in a uniform fashion such that the CH...O bonds all remain weaker than OH...O in any solvent. These H-bond weakenings are coupled to a shortening of the inter-subunit separation. The contraction of the covalent CH bond to the bridging proton is reduced as the solvent becomes more polar, and the blue shift of its stretching vibration is likewise diminished. A process is considered that simulates protein folding by starting from a pair of noninteracting subunits in aqueous solvent and then goes to a H-bonded pair within the confines of a protein environment. This process is found to be energetically more favorable for some of the CH...O H-bonds than for the nominally stronger conventional OH...O H-bond. This finding suggests that CH...O bonds can make important energetic contributions to protein folding, on par with those made by traditional H-bonds.     

A guest-induced reversible switching of a self-assembled H-bonded supramolecular framework

A new class of organic crystalline 2,2'-biphenol-based H-bonded material displaying 1D-channels encapsulating solvent molecules is described. A reversible guest-induced crystal-to-crystal conversion between the solvated H-bonded phase and a compact H-bonded non-solvated phase was observed. The energy competition between intramolecular H-bonds formation and solvation of organic pores has been characterized using PACHA calculations.     

Cooperative Hydrogen Bonding in Glyco–Oligoamides: DNA Minor Groove Binders in Aqueous Media

A strategy to create cooperative hydrogen‐bonding centers by using strong and directional intramolecular hydrogen‐bonding motifs that can survive in aqueous media is presented. In particular, glyco–oligoamides, a family of DNA minor groove binders, with cooperative and non‐cooperative hydrogen‐bonding donor centers in the carbohydrate residues have been designed, synthesized, and studied by means of NMR spectroscopy and molecular modeling methods. Indeed, two different sugar moieties, namely, β‐D ‐Man‐Py‐γ‐Py‐Ind ( 1 ; Ind=indole, Man=mannose, Py=pyrrole) and β‐D ‐Tal‐Py‐γ‐Py‐Ind ( 2 ; Tal=talose), were chosen according to our design. These sugar molecules should present one‐ or two‐directional intramolecular hydrogen bonds. The challenge has been to study the conformation of the glyco–oligoamides at low temperature in physiological media by detecting the exchangeable protons (amide NH and OH resonances) by means of NMR spectroscopic analysis. In addition, two more glyco–oligoamides with non‐cooperative hydrogen‐bonding centers, that is, β‐D ‐Glc‐Py‐γ‐Py‐Ind ( 3 ; Glc=glucose), β‐D ‐Gal‐Py‐γ‐Py‐Ind ( 4 ; Gal=galactose), and the model compounds β‐D ‐Man‐Py‐NHAc ( 5 ) and β‐D ‐Tal‐Py‐NHAc ( 6 ) were synthesized and studied for comparison. We have demonstrated the existence of directional intramolecular hydrogen bonds in 1 and 2 in aqueous media. The unexpected differences in terms of stabilization of the intramolecular hydrogen bonds in 1 and 2 relative to 5 and 6 promoted us to evaluate the influence of CH—π interactions on the establishment of intramolecular hydrogen bonds by using computational methods. Initial binding studies of 1 and 2 with calf‐thymus DNA and poly(dA‐dT)₂ by NMR spectroscopic analysis and molecular dynamics simulations were also carried out. Both new sugar–oligoamides are bound in the minor groove of DNA, thus keeping a stable hairpin structure, as in the free state, in which both intramolecular hydrogen‐bonding and CH—π interactions are present.     

分子烙印聚合物作为高效毛细管电泳添加剂的研究

分子洛印聚合物（molecular imprinted polymer)是一种高选择的有分子记忆效应的主体分子,通常在非极性环境中制备和应用。该文在极性溶剂中利用离子化作用和疏水作用制备了非共价的分子烙印聚合物,并将其作为高效毛细管电泳流动相添加剂;在含水缓冲溶液条件下,研究了单体种类、分子烙印聚合物颗粒度和含量、缓冲溶液pH值以及分离电压对分子烙印聚合物识别模板分子的影响。结果证明了在质子溶剂中制备和应用非共价分子烙印聚合物是可行的。     

Degradable Hybrid Materials Based on Cationic Acylhydrazone Dynamic Covalent Polymers Promote DNA Complexation through Multivalent Interactions

The design of smart nonviral vectors for gene delivery is of prime importance for the successful implementation of gene therapies. In particular, degradable analogues of macromolecules represent promising targets as they would combine the multivalent presentation of multiple binding units that is necessary for achieving effective complexation of therapeutic oligonucleotides with the controlled degradation of the vector that would in turn trigger drug release. Toward this end, we have designed and synthesized hybrid polyacylhydrazone‐based dynamic materials that combine bis‐functionalized cationic monomers with ethylene oxide containing monomers. Polymer formation was characterized by ¹H and DOSY NMR spectroscopy and was found to take place at high concentration, whereas macrocycles were predominantly formed at low concentration. HPLC monitoring of solutions of these materials in aqueous buffers at pH values ranging from 5.0 to 7.0 revealed their acid‐catalyzed degradation. An ethidium bromide displacement assay and gel electrophoresis clearly demonstrated that, despite being dynamic, these materials are capable of effectively complexing dsDNA in aqueous buffer and biological serum at N/P ratios comparable to polyethyleneimine polymers. The self‐assembly of dynamic covalent polymers through the incorporation of a reversible covalent bond within their main chain is therefore a promising strategy for generating degradable materials that are capable of establishing multivalent interactions and effectively complexing dsDNA in biological media.     

Quantitative FTIR study of PHBV/bisphenol A blends

FTIR spectroscopy was used to verify the presence of intermolecular hydrogen bond (inter-H-bond) between poly(3-hydroxybutyrate co-3-hydroxyvalerate) (PHBV) and bisphenol A (BPA). By monitoring the spectral changes during PHBV crystallization and blends dissociation, the absorptivity ratio of CO bonds in crystalline and amorphous regions in PHBV and that of H-bonded and free CO in PHBV/BPA blends were experimentally determined as 1.40 and 1.68, respectively. Using curve-fitting program, the CO absorptions in spectra of blends were ascribed to three types of bonds: amorphous, crystalline and H-bonded CO. The crystallinity of PHBV and the fraction of H-bonded CO were calculated. These results indicated that the H-bond clearly suppressed the PHBV crystallization. Furthermore, the fraction of BPA molecules that simultaneously formed two hydrogen bonds (H-bonds) with CO was estimated. It revealed that there existed a H-bond network in PHBV/BPA blends. This network was compared with the covalent network by estimating the number of atoms between every two adjacent crosslink points in chain. Up to the high density of H-bond discussed in this paper, there was always a certain part in PHBV that crystallized due to the dynamic character of hydrogen bonds; however, the hydrogen bonds significantly reduced the crystallization rate of PHBV.     

Selective glycoprotein detection through covalent templating and allosteric click-imprinting

Many glycoproteins are intimately linked to the onset and progression of numerous heritable or acquired diseases of humans, including cancer. Indeed the recognition of specific glycoproteins remains a significant challenge in analytical method and diagnostic development. Herein, a hierarchical bottom-up route exploiting reversible covalent interactions with boronic acids and so-called click chemistry for the fabrication of glycoprotein selective surfaces that surmount current antibody constraints is described. The self-assembled and imprinted surfaces, containing specific glycoprotein molecular recognition nanocavities, confer high binding affinities, nanomolar sensitivity, exceptional glycoprotein specificity and selectivity with as high as 30 fold selectivity for prostate specific antigen (PSA) over other glycoproteins. This synthetic, robust and highly selective recognition platform can be used in complex biological media and be recycled multiple times with no performance decrement.     

Arrangement and nature of intermolecular hydrogen bonding in complex biomolecular systems: modeling the vitamin C---L-alanine interaction

Vitamin C is known as an essential dietary supplement and implicated in diverse biological processes. We present here a theoretical study on the nature of hydrogen bonding of vitamin C in biological systems. For this reason, the complexes of vitamin C (VC) with neutral and zwitterionic L-alanine (as the simplest chiral amino acid) were studied at the MP2/6-311++G(d,p) level of theory. In the gas phase, neutral L-alanine leads to more stable complexes than the zwitterionic forms while the reverse is true in the aqueous phase. The complexes are formed via two hydrogen bond interactions, which result in a ring-like hydrogen-bonded networks. The nature of H-bonds was characterized in terms of natural bond orbital and quantum theory of atoms in molecule analyses (QTAIM). The H-bonds in the studied complexes were electrostatic in nature; however, in the case of shorter and directional H-bonds and ionic interactions, contributions of covalent character were also non-negligible. Natural energy decomposition analysis of hydrogen-bonded complexes reveals that the charge transfer and electrical components are the largest contributors for the interaction energies of complexes. Natural resonance theory analysis suggests higher resonance weight for charge-assisted interactions of vitamin C---alanine (zwitterionic) complexes, where the total interaction energy is considerably higher than that of neutral alanine.     

Hydration of sulfonated polyimide membranes. II. Water uptake and hydration mechanisms of protonated homopolymer and block copolymers

The hydration of sulfonated polyimide membranes in their protonated form is probed by infrared spectrometry using a recently described method. The membranes considered are the homopolymer, made of identical sulfonated repeat units, and two block copolymers composed of these units plus similar ones with no sulfonic groups in two different proportions. The experiments consist of registering series of spectra of these membranes at various hygrometries of the surrounding atmosphere. The quantitative analysis of the evolution of these spectra allows one to measure precisely the water uptake and to define in terms of chemical reactions the various hydration mechanisms that are active at a definite value of the hygrometry. It shows how the dried homopolymer significantly differs from the two dried block copolymers: in the homopolymer, a good proportion of SO(3)H groups that represent 83% of sulfonate groups, cannot establish H-bonds on C=O groups that are in a relatively small number. As a consequence, all coexisting SO(3)(-) groups are H-bonded to single H(3)O(+) cations with no extra H(2)O molecules. In both dried block copolymers, each SO(3)H group (60% of the sulfonate groups) establishes H-bonds on C=O groups that are in a sufficiently great number. These H-bonds stabilize these SO(3)H groups, and coexisting SO(3)(-) groups are H-bonded to cations that are found in the form of H(5)O(2)(+) or H(7)O(3)(+) that contain several H(2)O molecules. When the hygrometry increases, these differences get less marked but can be precisely defined.     

Non‐covalent Versus Covalent Control of Self‐Assembly and Chirality of Nile Red‐modified Nucleoside and DNA

A DNA‐based covalent versus a non‐covalent approach is demonstrated to control the optical, chirooptical and higher order structures of Nile red ( Nr ) aggregation. Dynamic light scattering and TEM studies revealed that in aqueous media Nr ‐modified 2′‐deoxyuridine aggregates through the co‐operative effect of various non‐covalent interactions including the hydrogen bonding ability of the nucleoside and sugar moieties and the π‐stacking tendency of the highly hydrophobic dye. This results in the formation of optically active nanovesicles. A left‐handed helically twisted H‐type packing of the dye is observed in the bilayer of the vesicle as evidenced from the optical and chirooptical studies. On the other hand, a left‐handed helically twisted J‐type packing in vesicles was obtained from a non‐polar solvent (toluene). Even though the primary stacking interaction of the dye aggregates transformed from H→J while going from aqueous to non‐polar media, the induced supramolecular chirality of the aggregates remained the same (left‐handed). Circular dichroism studies of DNA that contained several synthetically incorporated and covalently attached Nr ‐modified nucleosides revealed the formation of helically stacked H‐aggregates of Nr but—in comparison to the noncovalent aggregates—an inversed chirality (right‐handed). This self‐assembly propensity difference can, in principle, be applied to other hydrophobic dyes and chromophores and thus open a DNA‐based approach to modulate the primary stacking interactions and supramolecular chirality of dye aggregates.     

Interaction of carboxylated polyacrylamide with chromium(III) acetate: 13C NMR study of mechanism

The interaction of chromium(III) acetate with poly(acrylamide-co-acrylic acid) in aqueous medium leads to formation of three-dimensional network of crosslinked macromolecules. Formation of the complex between chromium(III) cation and carboxylate groups is a driving force of the interaction. Depending on the reagents ratio, the complex contains two or three carboxylate groups. The amide units are not involved in any specific interaction with the cation.     

Study of H-bond characteristics in sub- and supercritical methanol

Classical molecular dynamics simulations of various methanol phase lines near the saturation curve and the critical point have been performed to study the changes in H-bonded clusters structure at transition of methanol to supercritical state. Analysis of H-bonds statistics with combined distance-energy H-bond criterion showed that the correlations between topological characteristics of H-bonds and the mole fraction of H-bonded molecules have unique functional representation despite the phase path applied. In the present study, an attempt has been also made to evaluate the degree of hydrogen bonding by combining the DFT computations on classical MD configurations with the natural bond orbital analysis of the waves functions obtained.     

Nonpolar, polar, and associating solutes in ionic liquids

The existence of microphase segregation between polar and nonpolar domains in ionic liquids changes the way in which solvation can be understood in these media. Here, we perform a structural analysis on the solvation of nonpolar, polar, and associating solutes in imidazolium-based ionic liquids, where this novel way of understanding their nature as microsegregated solvents is correlated with their ability to interact with different species in diverse and complex ways.     

Rapid construction of shape-persistent H-bonded macrocycles via one-pot H-bonding-assisted macrocyclization

The study of macrocycles has crossed many traditional disciplines such as chemistry, physics, biology, medicine and engineering with many research areas concentrating on specific and selective molecular recognition, self-organisation and its already demonstrated and other promising applications. Compared to traditional strategies to synthesize macrocycles with widely ranging structures using such as templated cyclization or dynamic covalent bond formation, one-pot H-bonding-assisted macrocyclization has been shown to provide a simple, fast and cost-efficient method to synthesize shape-persistent H-bonded macrocycles of varying types containing an internal cavity of as large as 2.9 nm in diameter. This review will summarize the recent works on such “greener” syntheses of H-bonded macrocycles that help to create a whole new dimension of research and to offer a new bottom-up strategy for constructing functional architectures and materials.     

A Dynamic Chemical Network for Cystinuria Diagnosis

The study of molecular networks represents a conceptual revolution in chemistry. Building on previous knowledge and after understanding the rules of non‐covalent interactions, the design of stimulus‐responsive chemical systems is possible. Herein we report a new strategy, based on the reorganization of a dynamic chemical network that generates new fluorescent associations in the presence of cysteine or cystine. The binding and sensing units are encoded in the components that dynamically assemble and disassemble responding to external stimuli as a successful tool to detect both cysteine and cystine in aqueous media. Moreover, the dynamic sensing system works in human urine, as a prospective application for cystinuria diagnosis.