H-bonded Systems Research Articles

Enantioselective Sulfur‐Michael Addition of Thioacetic Acid to Nitroalkenes Catalyzed by Bifunctional Amine‐Thiourea Catalysts

AbstractAn enantioselective Michael addition of thioacetic acid (AcSH) to nitroalkenes, catalyzed by a leucine‐derived bifunctional aminethiourea, was developed with high yields and moderate enantioselectivities. The thiourea‐ammonium salt formed in the reaction is identified as the active catalyst, and the multiple H‐bonding system is responsible for the stereocontrol. The resulting thioester products are useful intermediates for the synthesis of enantiomerically enriched S‐containing compounds.

Spectroscopy and molecular docking studies on the binding of propyl gallate to human serum albumin

The interaction of propyl gallate (PG) with human serum albumin (HSA) was investigated by fluorescence, far-UV CD and FT-IR spectroscopic methods as well as molecular docking. Fluorescence emission spectra demonstrated that the HSA fluorescence was quenched by PG through static quenching and energy transfer with the binding constants in the order of 105Lmol−1. The thermodynamic parameters (ΔH=−29.64KJmol−1, ΔS=2.7Jmol−1K−1) indicated that both hydrophobic force and hydrogen bond interactions played a leading role in the formation of PG–HSA complex. The results also showed the existence of a single binding site, which was located in subdomain IIA (site I) as revealed by molecular docking and competitive binding experiments. Molecular docking studies further showed the participation of several amino acids in PG–HSA complexation, which stabilized by H-bonding systems. The synchronous fluorescence spectra showed that the binding of drug caused the environment of tryptophan residues became more polar. FT-IR and CD spectroscopic further showed that drug complexation altered protein conformation by a major reduction of α-helix inducing a partial protein destabilization.

ChemInform Abstract: Nano‐ and Microstructuration of Supramolecular Materials Driven by H‐Bonded Uracil·2,6‐diamidopyridine Complexes

AbstractReview: 131 refs.

Core level crystallography: Probing H-bonding through nitrogen XPS and NEXAFS

Determining the location of hydrogen is not always straightforward, despite its potential for wide-reaching effects, such as altering physicochemical properties and biological/chemical processes. Proton transfer can be considered a simple chemical reaction, with a continuum from neutral to protonated states, and short, strong H-bonds (SSHB) and disordered systems between the two extremes. X-ray Photoelectron Spectroscopy (XPS) and Near Edge X-ray Absorption Fine Structure (NEXAFS) intrinsically probe the local environment, with sensitivity to the chemical state of the atom and, importantly, nature of the local chemical and bonding environment. Organic molecular crystals have been studied by nitrogen XPS and NEXAFS, offering an alternative to X-ray and neutron diffraction. Strong chemical shifts occur with proton transfer to nitrogen (+N-H---O vs. N---H-O), unambiguously characterizing protonated and H-bonded systems,[1] leading to direct observation of an unusual solid-state colour change for 4,4'-bipyridine/squaric acid with heating[2] involving proton transfer to nitrogen with temperature-dependent measurements. Correlation between H-bond lengths and chemical shifts indicates potential for predicting H-bond lengths. SSHBs provide an interesting case, as hydrogen can reside midway between donor and acceptor, having a 3-centre, 4-electron bond with quasi-covalent character and atypical properties. Intermediate chemical shifts are found with hydrogen midway between donor and acceptor in 3,5-pyridinedicarboxylic acid, with increased peak width representative of hydrogen's broadened single minimum potential well.[3] This contrasts with conventional 2-site hydrogen disorder, in which signals from both donor and acceptor environments result in 2 peaks reflecting the % occupancy. Valuable electronic and structural information is obtained from the variety of organic systems investigated, with XPS clearly distinguishing different types of crystallographic materials (Fig 1).

Non-covalent interactions of Acipimox in Multi-component Crystals

The hypolipidemic agent acipimox has various potential hydrogen bonding donor and acceptor sites. A series of multi-component crystals can be formed owing to these moieties. Acipimox forms such structures with benzamide, isonicotinamide and urea. Each of these systems has a unique hydrogen bonding arrangement leading to changes in the physicochemical properties of acipimox. X-ray analysis of a hydrated co-crystal, acipimox·benzamide·0.5H2O (space group C2/c) revealed layers of dimeric acipimox-benzamide units, the layers being linked by hydrogen bonding from a bridging water molecule. A salt with formula (acipimox)- (isonicotinamide)+ (space group P2(1)/c) results from proton transfer from the carboxyl group of acipimox to the pyridyl nitrogen of isonicotinamide. The carboxyl group engages in an electrostatic interaction with the protonated pyridyl nitrogen. In addition, a hydrogen bond is formed between the donor amide and the acceptor carboxyl group of a second acipimox anion. These form a macrocyclic structure composed of two pairs of acipimox-isonicotinamide counterions in a R44(22) H-bonded motif, giving rise to interlaced layers. Acipimox and urea form two distinct systems, both crystallising in the space group P(-1). The kinetic crystallisation product is a co-crystal with 1:1 acipimox:urea stoichiometry (R22(8) motif), a second distinct urea molecule self-assembles forming infinite chains within channels formed by the packing arrangement. The thermodynamic form is an acetonitrile solvate in which the solvent molecules are included in isolated sites. The different H-bonding systems in each of these multi-component crystals give rise to differing physicochemical properties. For example the melting and degradation temperatures for each of these systems is distinct: that of the acipimox·benzamide co-crystal is lower than that of acipimox while the crystals containing isonicotinamide and urea have higher melting and degradation temperatures.

Cocrystallization of acetaminophen and glutaric acid with different coformers

Recently cocrystallization became a popular tool for crystal engineering that allows, for instance, improving properties of pharmaceutical materials, creating new materials for nonlinear optical applications and solar cell technologies. To attract students to crystallographic studies we carried out project that included crystal growth of two series of cocrystals with acetaminophen and with dicarbonic glutaric acid. We attempted cocrystallization of acetaminophen with more than ten different coformers which gave no cocrystals or salts. However, as a result of cocrystallization we obtained new polymorph modification of hydroxyquinoline. On the contrary, cocrystallization of glutaric acid with basic organic compounds gave several new salts. Interesting examples among them are systems of glutaric acid with 2-pyridinamine and with 6-methyl-2-pyridinamine. In spite of the presence of the same substituents that are prone to H-bond formation, cocrystals have different H-bonding systems and even different molecular conformation of glutaric acid. Details of physical properties, such as spectral characteristics and melting points, of obtained multicomponent materials are discussed.

Hydroxyl radical recycling in isoprene oxidation driven by hydrogen bonding and hydrogen tunneling: the upgraded LIM1 mechanism.

The Leuven isoprene mechanism, proposed earlier to aid in rationalizing the unexpectedly high hydroxyl radical (OH) concentrations in isoprene-rich, low-nitric-oxide (NO) regions ( Peeters ; et al. Phys. Chem. Chem. Phys . 2009 , 11 , 5935 ), is presented in an upgraded and extended version, LIM1. The kinetics of the crucial reactions in the proposed isoprene-peroxy radical interconversion and isomerization pathways are re-evaluated theoretically, on the basis of energy barriers computed at the much higher CCSD(T)/aug-cc-pVTZ//QCISD/6-311G(d,p) level of theory, and using multiconformer partition functions obtained at the M06-2X/6-311++G(3df,2p) level that, different from the B3LYP level used in our earlier work, accounts for the crucial London dispersion effects in the H-bonded systems involved. The steady-state fraction of the specific Z-δ-OH-peroxy radical isomers/conformers that can isomerize by a 1,6-H shift is shown to be largely governed by hydrogen-bond strengths, whereas their isomerization itself is found to occur quasi-exclusively by hydrogen atom tunneling. The isomer-specific Z-δ-OH-peroxy 1,6-H-shift rate coefficients are predicted to be of the order of 1 s(-1) at 298 K, but the experimentally accessible bulk rate coefficients, which have to be clearly distinguished from the former, are 2 orders of magnitude lower due to the very low Z-δ-OH-peroxy steady-state fractions that are only around or below 0.01 at low to moderate NO and depend on the peroxy lifetime. Two pathways subsequent to the peroxy radical 1,6-H shift are identified, the earlier predicted route yielding the photolabile hydroperoxy-methylbutenals (HPALDs), and a second, about equally important path, to dihydroperoxy-carbonyl peroxy radicals (di-HPCARP). Taking this into account, our predicted bulk peroxy isomerization rate coefficients are about a factor 1.8 higher than the available experimental results for HPALD production ( Crounse ; et al. Phys. Chem. Chem. Phys. 2011 , 13 , 13607 ), which is within the respective uncertainty margins. We also show that the experimental temperature dependence of the HPALD production rates as well as the observed kinetic isotope effect for per-deuterated isoprene support quantitatively our theoretical peroxy interconversion rates. Global modeling implementing LIM1 indicates that on average about 28% of the isoprene peroxys react via the 1,6-H-shift isomerization route, representing 100-150 Tg carbon per year. The fast photolysis of HPALDs we proposed earlier as primary OH regeneration mechanism ( Peeters and Muller . Phys. Chem. Chem. Phys . 2010 , 12 , 14227 ) found already experimental confirmation ( Wolfe ; et al. Phys. Chem. Chem. Phys. 2012 , 14 , 7276 ); based on further theoretical work in progress, reaction schemes are presented of the oxy coproduct radicals from HPALD photolysis and of the di-HPCARP radicals from the second pathway following peroxy isomerization that are both expected to initiate considerable additional OH recycling.

PH-stability and pH-annealing of H-bonded multilayer films prepared by layer-by-layer spin-assembly

Spin-assisted assembly and pH-induced disintegration of H-bonded multilayers of poly(N-vinylpyrrolidone) and tannic acid (PVPON/TA) have been investigated. Multilayers showed significantly different pH-induced disintegration profiles depending on how long the multilayers were kept in the dry state between exposures to buffer solutions indicating relaxations of the molecules. To understand the effect of kinetic trapping and the consequent relaxations towards equilibrium on the pH-stability of H-bonded PVPON/TA spin-LbL multilayers, spin-coated multilayers were prepared at different nonequilibrium states by varying the spinning rate and the solution-film static contact time. The pH-stability of multilayers increased with increasing spinning rate and decreasing static contact time. The gradual decrease of bilayer thickness with increasing spinning rate indicated the flattening of the molecules. The enhancement of the pH-stability of multilayers was attributed to both the flattening and the relaxations of molecules having nonequilibrium conformations. A transition from linear to exponential growth profiles was observed with increasing static contact times indicating in and out diffusion in PVPON/TA system. pH-treatment of multilayers just below the critical disintegration pH, a process we call pH-annealing, enhanced their pH-stability significantly. Multilayers annealed longer at pH 7.0 showed better pH-stability (up to 1h) at pH 9.0 whereas nonannealed films disintegrated within 10min. The introduced pH-annealing process is promising for practical applications of H-bonded systems such as controlled drug delivery.

Electrochemical Characterization of an Electroactive Ureidopyrimidinone Derivative, a Four Hydrogen Bond Array Containing a Dimethylaminophenylurea

Electron transfer reactions can be used to perturb the strength of hydrogen bonding interactions between organic molecules. When molecular redox centers are integrated onto hydrogen bond arrays, this combination can become a powerful tool for controlling binding strength in supramolecular complexes. Whether used for sensing devices, molecular machines or self-assembly, the strength of a hydrogen bond can also be enhanced simply by arrangement of hydrogen donor interactions (D) versus hydrogen acceptor interactions (A). Indeed, because of secondary interactions, dimerization constants of the DDAA 4 H-Bond array typically exceed that of the DADA 4 H-Bond array.1 By combining a DDAA 4 H-bond array such as Meijer’s ureidopyrimidinone1with an electroactive center such as the dimethylaminophenylurea, the strength of hydrogen bonding becomes tunable.Cyclic voltammetry investigation, in nonaqueous solvents, of dimethylaminophenylurea (UHH), a DD 2H-bond array, show that without a guest present, there is one reversible oxidation wave in methylene chloride of one electron height. CV Digital simulations as well as UV-vis spectroelectrochemistry indicate a proton transfer from the radical species to the reduced U(H)H, followed by another electron transfer due to potential inversion to give the quinoidal cation, Scheme 1. With the integration of the dimethylphenylamino redox center, this mechanism would certainly complicate the dimerization of Meijer’s DDAA array.Scheme 1. Proposed oxidation mechanism of UHH undergoing an overall one electron transfer due to proton transfer.Due to the acidity of the urea NH that is part of the electroactive center, proton transfer could also occur as part of the electrochemistry associated with the DDAA dimer. We hypothesize that depending on the ratio of arrays substituted with an electroactive center versus those without, the DDAA sequence could change to a DDAD array. With all arrays containing an electroactive center the hydrogen bonding array would form an ADDA homodimer.This presentation will cover cyclic voltammetry studies that includes concentration and scan rate dependence investigations on Meijier’ DDAA dimer equipped with a dimethyphenylurea electroactive center. Digital CV simulations and spectroelectrochemistry will be used to analyze experimental CV ‘s.Figure 1. Meijer’s ureidopyrimidinone (Upy) 4 H-bond system without redox functionality as a DDAA homodimer.Figure 2. Structure of the proposed heterodimer, DDAD array, as a result of half the concentration with an electroactive center and the other half without.

Molecular Interaction of Amino Acids with Acidic Zeolite BEA: The Effect of Water

Experimentally, zeolites were shown to adsorb amino acids from the aqueous phase. However, there has not been a satisfactory theoretical explanation on the effect of water on the underlying adsorption mechanisms yet. In this study, the effect of water on the pH-dependent adsorption behavior of glycine and alanine in zeolite BEA was investigated using density functional theory (DFT). Using a microsolvation model, the coadsorption and formation of an intermolecular H-bond system between water molecules, amino acid, and zeolite was shown. In addition, different pH values were modeled by varying the amino acids protonation states with the protonated states being significantly more stable in the BEA pores than the net neutral ones. This behavior was experimentally approved by isothermal titration calorimetry (ITC) and adsorption isotherm measurements. These results provide new molecular level information on the adsorption of amino acids in zeolites from the aqueous phase and could be used to support the experi...

Hydrogen-bonded complexes upon spatial confinement: structural and energetic aspects

In the present study we consider structural and energetic aspects of spatial confinement of the H-bonded systems. The model dimeric systems: HF···HF, HCN···HCN and HCN···HCCH have been chosen for a case study. Two-dimensional harmonic oscillator potential, mimicking a cylindrical confinement, was applied in order to render the impact of orbital compression on the analyzed molecular complexes. The calculations have been performed employing the MP2 method as well as the Kohn-Sham formulation of density functional theory. In the latter case, two exchange-correlation potentials have been used, namely B3LYP and M06-2X. The geometries of studied complexes have been optimized (without any constraints) in the presence of the applied model confining potential. A thorough analysis of topological parameters characterizing hydrogen bonds upon orbital compression has been performed within the Quantum Theory of Atoms in Molecules (QTAIM). Furthermore, an energetic analysis performed for the confined H-bonded complexes has shown a different trend in the interaction energy changes. Additionally, a variational-perturbational decomposition scheme was applied to study the interaction energy components in the presence of spatial confinement.

Effect of synthetic polymers on polymer–protein interaction

Synthetic polymers are often used for delivery of therapeutic drugs and proteins. We report the binding of milk β-lactoglobulin (β-LG) with poly(ethylene glycol) (PEG), methoxypoly(ethylene glycol) polyamidoamine (mPEG-PAMAM-G-3) and polyamidoamine (PAMAM-G4) nanoparticles in aqueous solution at pH 7.4, using Fourier Transform infrared (FTIR), circular dichroism (CD), fluorescence spectroscopic methods, transmission electron microscopy (TEM) and molecular modeling. Structural analysis showed that polymers bind β-LG via both hydrophilic and hydrophobic contacts with overall binding constants KPEG-8000-β-LG = 4.8 (±0.4) × 104 M−1 and KmPEG-PAMAM-G3-β-LG = 5.8 (±0.6) × 105 M−1 and KPAMAM-G4-β-LG = 6.7 (±0.9) × 104 M−1. The number of binding sites were occupied by polymers on protein (n) was 0.3 for PEG-8000, 0.4 for mPEG–PAMAM-G3 and 0.4 for PAMAM-G4. The order of binding is mPEG-PAMAM-G3 > PAMAM-G4 > PEG-8000. Transmission electron microscopy showed significant changes in protein morphology as polymer–protein complexation progressed with major increase in the diameter of the protein aggregate (180%). Furthermore, modeling showed several H-bonding systems between PEG and different amino acids stabilize polymer–β-LG complexes. mPEG-PAMAM-G3 is a stronger protein binder than PAMAM-G4 and PEG-8000.

Infrared Spectra and Structure of Poly(Vinylalcohol) Films Obtained From Aqueous Solutions with Potassium Iodide Additive

The crystallinity and H-bonds in poly(vinylalcohol) films obtained from aqueous solutions with potassium iodide additive were investigated by IR spectroscopy. It was established that addition of KI caused the degree of polymer crystallinity to increase. The band of hydroxyl stretching vibrations (νOH) shifted toward higher frequency in spectra of films with KI additive. This indicated a change in the system of H-bonds in the polymer. The dependences of both the degree of crystallinity and the shift of the νOH band on the salt concentration were qualitatively different in shape.

Molecular Tuning of the Closed Shell C–H···F–C Hydrogen Bond

The existence of the rare six-membered and intramolecular C-H···F-C hydrogen-bond has been experimentally proven in the gas phase and in the solid state recently. However, the effect of the substituents on this C-H···F-C hydrogen-bond system has never been reported. In view of the importance of this type of C-H···F-C H-bonding whose weak interaction has been found critical in nanotechnology and biological systems, the nine functional groups composed of electron donating and electron withdrawing groups are inserted into this C-H···F-C interaction to study the group effect on the hydrogen bonding. Group effects on this C-H···F-C H-bonding system have been found, and their effects on the H-bonding system have been found to be tunable.

Dynamics of H-Bonded Systems in Nanosized Pores

Dynamics of H-Bonded Systems in Nanosized Pores

Characteristic NMR spectra of proton transfer in protonated water clusters

Characteristic NMR spectra of proton transfer in protonated water clusters were studied using the H+(H2O)n complexes, n=2−5, as model systems, and ab initio calculations at the RIMP2/TZVP level and BOMD simulations as model calculations. Based on the concept of presolvation, two-dimensional potential energy surface of proton in the smallest, most active intermediate complex (the Zundel complex) was constructed as a function of the H-bond distance (RO–O) and the asymmetric stretching coordinate (ΔdDA). The low-interaction energy path and the path with ΔdDA=0Å were analyzed and discussed in comparison with the model systems. The two proton transfer paths associate with the characteristic IR frequencies namely, the structural diffusion and oscillatory shuttling frequencies, respectively. RIMP2/TZVP calculations showed that the proton moving on the oscillatory shuttling path is characterized by the 1H NMR shielding constant (σH+corr) varying in a narrow range, whereas on the structural diffusion path, σH+corr changes exponentially with RO–H. The energetic, dynamic and spectroscopic results obtained from BOMD simulations in the temperature range between 350 and 450K validated the presolvation model and revealed that the activation energies for the proton exchange in the smallest, most active intermediate complex, computed from the Arrhenius equation, IR spectra and a simple 1H NMR line shape analysis, are consistent and in good agreement with experiments in aqueous solution. Based on the presolvation model and the outstanding characteristics of the IR and 1H NMR spectra of the transferring protons, the present theoretical study suggested framework and steps to investigate structural diffusion processes in strong, protonated H-bond systems.

An unusually water-poor 5,5′-azobistetrazolate of dysprosium: stabilization of a nitrogen-rich heterocycle by a minimum of hydrogen bonds

In inorganic 5,5′-azobistetrazolate (C2N102−; ZT) compounds, the energetic ZT moiety is usually stabilized by H-bonds to lattice H2O and/or coordination of an N-atom of the tetrazole ring to the metal ion. Here we present the synthesis and characterization of a novel, salt-like compound, [Dy(H2O)8]2ZT3, which constitutes a unique exception to the above rule. We used supercritical CO2 as an unconventional desiccant in a straightforward metathesis reaction without abstaining from the benefits aqueous chemistry offers. It caused the crystallization of the title compound with a complex system of H-bonds between [Dy(H2O)8]3+ and ZT2− that involves almost every N-atom of the ZT2− anions as H-bond acceptors, which sufficiently stabilizes the energetic ZT despite the lack of lattice H2O or a coordinative bond to the metal ion.

Hydrogen-bonds in molecular solids - from biological systems to organic electronics.

Hydrogen-bonding (H-bonding) is a relatively strong, highly directional, and specific noncovalent interaction present in many organic molecules, and notably is responsible for supramolecular ordering in biological systems. The H-bonding interactions play a role in many organic electrically conducting materials - in particular in those related to biology, e.g. melanin and indigo. This article aims to highlight recent work on application of nature-inspired H-bonded organic molecules in organic electronic devices. Three topics are covered in this brief review: (1) electrical and ionic conduction in natural H-bonded systems, (2) semiconducting properties of H-bonded organic pigments, and (3) exploitation of H-bonding for supramolecular assembly of organic conductors. H-bonding interactions are ubiquitous in biology, thus making the study of H-bonded organic semiconductors highly pertinent where interfacing of electronics with biological systems is desired.

Nano- and microstructuration of supramolecular materials driven by H-bonded uracil·2,6-diamidopyridine complexes

In the last few decades, multiple H-bonded arrays have been shown to be versatile tools to prepare functional supramolecular materials. Supramolecular complexes formed by uracil (Ur) and 2,6-diamidopyridine (DAP) developed by Lehn are the first examples of multiple H-bonded systems governing the formation of supramolecular polymers in solution. Although a large variety of complementary multiple H-bonded complexes has been prepared, the use of the heteromolecular Ur·DAP complex still remains very promising due to its ease of preparation and its intermediate association strength that ensures a dynamical character to the self-assembly and self-organisation processes. In this feature article, we report a detailed account on the results that our group has obtained in this field by designing and engineering a novel library of shape persistent molecular modules able to transfer their geometrical information to the final supramolecular architectures through the formation of Ur·DAP complexes both at the nanoscopic and microscopic levels.

Phthalazine Derivatives Containing Imidazole Rings Behave as Fe-SOD Inhibitors and Show Remarkable Anti-T. cruzi Activity in Immunodeficient-Mouse Mode of Infection

A series of new phthalazine derivatives 1-4 containing imidazole rings were prepared. The monoalkylamino substituted derivatives 2 and 4 were more active in vitro against T. cruzi and less toxic against Vero cells than both their disubstituted analogues and the reference drug benznidazole. Compounds 2 and 4 highly inhibited the antioxidant parasite enzyme Fe-SOD, and molecular modeling suggested that they interact with the H-bonding system of the iron atom moiety. In vivo tests on the acute phase of Chagas disease gave parasitemia inhibition values twice those of benznidazole, and a remarkable decrease in the reactivation of parasitemia was found in the chronic phase for immunodeficient mice. Glucose metabolism studies showed that compounds 1-4 did not affect the succinate pathway but originated important changes in the excretion of pyruvate metabolites. The morphological alterations found in epimastigotes treated with 1-4 confirmed extensive cytoplasm damage and a high mortality rate of parasites.