Formation Of Intramolecular Hydrogen Bond Research Articles

Solution Conformations Shed Light on PROTAC Cell Permeability.

Proteolysis targeting chimeras (PROTACs) induce intracellular degradation of target proteins. Their bifunctional structure puts degraders in a chemical space where ADME properties often complicate drug discovery. Herein we provide the first structural insight into PROTAC cell permeability obtained by NMR studies of a VHL-based PROTAC (1), which is cell permeable despite having a high molecular weight and polarity and a large number of rotatable bonds. We found that 1 populates elongated and polar conformations in solutions that mimic extra- and intracellular compartments. Conformations were folded and had a smaller polar surface area in chloroform, mimicking a cell membrane interior. Formation of intramolecular and nonclassical hydrogen bonds, π–π interactions, and shielding of amide groups from solvent all facilitate cell permeability by minimization of size and polarity. We conclude that molecular chameleonicity appears to be of major importance for 1 to enter into target cells.

Amphiphilic Molecular Brushes with Regular Polydimethylsiloxane Backbone and Poly-2-isopropyl-2-oxazoline Side Chains. 2. Self-Organization in Aqueous Solutions on Heating.

The behavior of amphiphilic molecular brushes in aqueous solutions on heating was studied by light scattering and turbidimetry. The main chain of the graft copolymers was polydimethylsiloxane, and the side chains were thermosensitive poly-2-isopropyl-2-oxazoline. The studied samples differed in the length of the grafted chains (polymerization degrees were 14 and 30) and, accordingly, in the molar fraction of the hydrophobic backbone. The grafting density of both samples was 0.6. At low temperatures, macromolecules and aggregates, which formed due to the interaction of main chains, were observed in solutions. At moderate temperatures, heating solutions of the sample with short side chains led to aggregation due to dehydration of poly-2-isopropyl-2-oxazoline and the formation of intermolecular hydrogen bonds. In the case of the brush with long grafted chains, dehydration caused the formation of intramolecular hydrogen bonds and the compaction of molecules and aggregates. The lower critical solution temperature for solutions of the sample with long side chains was higher than LCST for the sample with short side chains. It was shown that the molar fraction of the hydrophobic component and the intramolecular density are the important factors determining the LCST behavior of amphiphilic molecular brushes in aqueous solutions.

The Influence of Weakly Coordinating Cations on the O-H⋅⋅⋅O- Hydrogen Bond of Silanol-Silanolate Anions.

The reaction of a saline phosphazenium hydroxide hydrate with siloxanes led to a novel kind of silanol‐silanolate anions. The weakly coordinating behavior of the cation renders the formation of silanol‐silanolate hydrogen bonds possible, which otherwise suffer from detrimental silanolate–oxygen cation interactions. We investigated the influence of various weakly coordinating cations on silanol‐silanolate motifs, particularly with regard to different cation sizes. While large cations favor the formation of intramolecular hydrogen bonds resulting in cyclic structures, the less bulky tetramethyl ammonium cation encourages the formation of polyanionic silanol‐silanolate chains in the solid state.

Competition between abiogenic and biogenic metal cations in biological systems: Mechanisms of gallium‘s anticancer and antibacterial effect

Metal cations are key players in a plethora of essential biological processes. Over the course of evolution specific biological functions have been bestowed upon two dozen of (biogenic) metal species, some of the most frequently found being sodium, potassium, magnesium, calcium, zinc, manganese, iron, and copper. On the other hand, there is a group of less studied abiogenic metals like lithium, strontium and gallium that possess not known functions in living organisms, but, by mimicking the native ions and/or competing with them for binding to key metalloenzymes, may exert beneficial effect on humans in particular medical conditions. This review summarizes and critically examines the mechanisms of gallium's therapeutic action in anticancer and antibacterial therapies by exploiting the tools of molecular modeling and experimental biochemistry. These approaches allow for identifying key factors for Ga3+ beneficial effect such as the electrostatic interactions with the protein ligands, substrates or bacterial siderophores, intramolecular hydrogen bond formation, and pH and dielectric properties of the medium. Several intriguing questions concerning the gallium competition with the native ferric ion have found their answers.

Atomistic investigation of GFRP composites under chloride environment

Fiber reinforced polymer composites have paved the way for the evolution of the engineering materials. Glass fiber reinforced polymer (GFRP) has become one of the most promising materials among the novel composites due to its low price and high performance. Here, the GFRP composite in investigated by fill atomistic molecular dynamics, which contains the epoxy matrix and amorphous silica substrate. The degradation in chloride environment is revealed through the interfacial interactions, the structural changes of the epoxy matrix and hydrogen bonding in the composites. Compared to dry and aqueous environment, the simulation results show that chloride environment leads to the worst deterioration of interfacial adhesion, which correlates with structural and mechanical degradation of bonded interface, as indicated by the decreased epoxy density close to interface. It is indicated by examining the nano-structures of the interface during the pulling process that the chloride environment hinders the formation of intramolecular and intermolecular hydrogen bonds in the GFRP composites. These findings indicate the deterioration towards bond and matrix is critical in the presence of the chloride environment, which provides the fundamental insight for designing and predicting performance degradation of macroscopic GFRP composites in the marine application.

Ethanol induced changes in structural, morphological, and functional properties of whey proteins isolates: Influence of ethanol concentration

The changes induced by ethanol treatments at different concentrations (20%, 40%, 60%, and 80%, v/v) on the structural, morphological and functional properties of native whey protein isolates (WPI) were investigated. The results showed that the secondary and tertiary structures of native WPI were clearly altered with ethanol treatment. The resulting molecular unfolding and subsequent aggregation was due to the formation of disulfide bonds and intramolecular hydrogen bonds, as well as hydrophobic interactions. Morphological observations revealed that ethanol treated WPI (E-WPI) had larger irregular block-shaped structures. Moreover, E-WPI prepared with an intermediate ethanol concentration (40% in our study) showed the highest emulsifying activity, emulsifying stability, foaming capacity, and surface hydrophobicity.

Substituent Pattern Effects on the Redox Potentials of Quinone-Based Active Materials for Aqueous Redox Flow Batteries.

Quinone‐based, aqueous redox flow batteries are a promising technology for large‐scale, low‐cost energy storage. To understand the influence of substituent and substituent pattern effects of quinone‐based derivatives on the redox potential, a screening study was performed that included benzoquinone, naphtaquinone, and anthraquinone derivatives. The order of substituent influence is −OH>−Me/−OMe for decreasing the redox potential and −F<−SO3 −<−CN, −NO2 for increasing the redox potential, which is in agreement with general expectations. We found that the consideration of resonance and inductive effects design strategies of redox‐active materials can be extended by the ability of intramolecular hydrogen bond formation, steric hindrance, and energetic differences of conformers for oxidized and reduced species. Due to the complexity and overlap of these effects, theoretical screening studies can provide guidance for the design of new molecular materials. In addition to the redox potential, other parameters such as stability, solubility, and kinetic rate constant or synthetic accessibility are crucial to consider.

A novel dimer-induced AIE material as a nano-sensor for colormetric and ratiometric sensing of Erythromycin and metal ions (Zn2+, Cd2+ and Cu2+) with different dissociation and re-aggregation processes and cellular imaging applications

We reported a sensor BZH bearing AIE (aggregation-induced emission) characteristics in solid state and aqueous ethanol solution. In EtOH/H2O (1/9, V/V) medium, BZH possessed spherical shape with the average diameter of ~142 nm due to the unique dimer formation by intermolecular hydrogen bonds, and exhibited fluorescence ratiometric response to Erythromycin, Zn2+ and Cd2+ and UV–vis ratiometric behavior to Cu2+ along with remarkable naked-eye color changes, respectively. The binding stoichiometry of BZH to Erythromycin was 2:1, but that to metal ions was 1:1. The BZH towards Erythromycin and metal ions showed different sensing mechanisms, and were confirmed by job'plot, 1H NMR FT-IR, ESI-MS, DLS and TEM. The presence of Erythromycin triggered the ESIPT process and induced new intramolecular hydrogen bond formation, but the presence of metal ions (Zn2+, Cd2+ and Cu2+) caused deprotonation processes, these caused the BZH dimers' dissociation and consequently induced monomer emission. Meanwhile, the morphology of BZH changed from spherical to flower shape for Erythromycin and block shape for metal ions, indicating the Erythromycin and metal ions with BZH monomer further formed new aggregates, respectively. Furthermore, the BZH was applied to detect Erythromycin, Zn2+, Cd2+ and Cu2+ in actual water samples and Hela cells.

Taking advantages of intramolecular hydrogen bonding to prepare mechanically robust and catalyst-free vitrimer

Fabrication of mechanically robust and catalyst-free vitrimers is of great importance, but often challenging. Herein, a facile strategy to achieve this goal by incorporation of intramolecular hydrogen bonds into the dynamic covalent network is demonstrated. Specifically, glycidyl methacrylate (GMA) is reacted with bio-renewable malic acid (MA) to generate a UV-curable resin containing ester linkages. On account of the proximity between the α-carbonyl and β-hydroxyl groups in MA, six-membered-ring intramolecular hydrogen bonds (O-H⋯O=C) are formed in the cross-linked network. This formation of intramolecular hydrogen bonds endows the network with enhanced and outstanding mechanical properties, showing tensile strength and Young's modulus of 117.7 MPa and 3.66 GPa, respectively. Meanwhile, the network is able to efficiently alter its topology without external catalyst through transesterifications reactions at high temperatures. We attributed this phenomenon to the presence of intramolecular hydrogen bonds which make the α-carbonyl carbon more positive and be more reactive towards nucleophilic attack, and thus facilitate the transesterification reaction. This work suggests a promising route to achieve catalyst-free thermosets with superior mechanical performances, good self-healing ability and reprocessability.

Effects of intramolecular hydrogen bond and electron delocalization on the basicity of proton sponges and superbases with benzene, pyridine, pyrazine and pyrimidine scaffolds

There are several classes of organic superbases whose basicity increases because of the formation of intramolecular hydrogen bond or/and of enhancement of electron delocalization in their protonated structures. In this work, effects of these two factors on the basicity of π-π and n-π conjugated nitrogen bases (mainly imines) are studied theoretically using the B3LYP/6-311++G(d,p) method. Comparison of proton affinities (PA) and gas phase basicities (GB) of investigated bases shows that change of electron delocalization after protonation in one ring enhances PA even by 30–40 kcal mol−1. Comparison of PAs of some proton sponges and “proton sponge-like” structures reveals that formation of a single hydrogen bond enhances PA by about 10 kcal mol−1. During this work, a large number of new superbases were designed and their basicities were assessed in the gas phase (with PA between 270 and 295 kcal mol−1) and acetonitrile (with pKa between 30 and 40).

A Facile Method to Synthesize Semicrystalline Poly(ester amide)s from 2,5-Furandicarboxylic Acid, 1,10-Decanediol, and Crystallizable Amido Diols

The synthesis of polyamides and poly(ester amide)s derived from 2,5-furandicarboxylic acid frequently leads to amorphous polymeric materials. Formation of intramolecular hydrogen bonds between the ...

Proton sponges and superbases with nitrogen, phosphorus, arsenic, oxygen, sulfur, and selenium as proton acceptor sites

Charge delocalization and intramolecular hydrogen bond formation in the protonated forms of organic bases with nitrogen, phosphorus, arsenic, oxygen, sulfur, and selenium as proton acceptor sites were investigated using B3LYP/6-311++G(d,p) method. Although the superbases with P and As atoms as proton acceptor site showed higher ability to delocalize the charge of the entering proton, because of the inherent basicity of nitrogen, the superbases with nitrogen atom were stronger bases. Proton sponges with N and O sites formed strong NH…N and OH…O hydrogen bonds. Generally, both the superbases and proton sponges with nitrogen atom as proton acceptor site exhibit higher basicity.

Effect of intramolecular hydrogen-bond formation on the molecular conformation of amino\xa0acids

The molecular conformation of the carboxyl group can be crucial for its chemical properties and intermolecular interactions, especially in complex molecular environments such as polypeptides. Here, we study the conformational behaviour of the model amino acid N-acetylproline in solution at room temperature with two-dimensional infrared spectroscopy. We find that the carboxyl group of N-acetylproline adopts two distinct conformations, syn- and anti-. In the syn-conformer the O–H group is oriented at ~60∘ with respect to the C=O and in the anti-conformer the O–H is anti-parallel to the C=O. In hydrogen-bond accepting solvents such as dimethyl sulfoxide or water, we observe that, similar to simple carboxylic acids, around 20% of the -COOH groups adopt an anti-conformation. However, when N-acetylproline is dissolved in a weakly hydrogen-bond accepting solvent (acetonitrile), we observe the formation of a strong intramolecular hydrogen bond between the carboxyl group in the anti-conformation and the amide group, which stabilizes the anti-conformer, increasing its relative abundance to ~60%.

Transition metal complexes with 2-acetylpyridine-ethylcarbazate: noncovalent interactions in their structures and antimicrobial studies

The 2-acetylpyridine-ethylcarbazate ligand (HL) formed four metal complexes, [Cu(HL)Cl2]⋅H2O (1), [Cu(HL)Br2]⋅H2O (2), [Zn(HL)Cl2] (3) and [Ni(L)2]⋅H2O (4). The carbazate and their metal complexes have been investigated by single crystal X-ray analysis, physicochemical, and spectroscopic methods. The Schiff base is coordinated to the metal ions as an anionic bi or tridentate ligand with the Z configuration about the imine C = N at the carbazate. Interactions in the crystal structures were analyzed using Hirshfeld surfaces and the 2D-fingerprint plots. Complexes 1, 2, and 3 present π⋅⋅⋅π stacking between the pyridyl rings with inter-centroid separations of 3.664(3)–3.887(2) Å. The water solvent molecules and the halogens allow the formation of intramolecular hydrogen bonds which close supramolecular structures in the molecular packing of the complexes. Free HL and 1–4 have been evaluated for antibacterial and antifungal activity against several multi-resistant bacteria and fungi. Significant antimicrobial activity of the complexes was observed; however, the free ligand and its complexes did not reveal any activity against some of the tested organisms.

Features of the Structural Organization and Sorption Properties of Cellulose

An improved model of the layered structure of cellulose microfibrils is proposed, taking into account the presence of slit-like pores between its structural elements. The scheme of the formation of donoracceptor intramolecular, intermolecular and interlayer hydrogen bonds of one glucopyranose unit in the cellulose crystallite is presented. The mechanism of specific adsorption interactions of water molecules in a monolayer with active centers located on the hydrophilic surfaces of elementary fibrils is described. The energy of dipole-dipole interactions was calculated depending on the distance between the active center and the adsorbate water molecule. The thermodynamic parameters characterizing the state of the adsorbate in the adsorption layers are determined by the proton magnetic relaxation method and sorption measurements. The possibility of determining the net heat of adsorption in a bilayer taking into account the Arrhenius nature of the correlation times of the thermal molecular motions of the adsorbate was established. An increase in the entropy of adsorbed water during the adsorption process was revealed. It was found that during adsorption, a part of the inner regions of crystallites transitions to their surface with the participation of cellulose hydroxyl groups, and during desorption, the reverse process is observed.

The binding mechanism of nitroreductase fluorescent probe: Active pocket deformation and intramolecular hydrogen bonds

Nitroreductase (NTR), a member of the flavoenzyme family, could react with nicotinamide adenine dinucleotide by reducing nitro to amino at hypoxic tumor, which can be monitored by some fluorescent probes in vivo. Here, molecular docking and molecular dynamics simulation techniques were used to explore the molecular mechanisms between NTR and probes. The results showed that formation of hydrogen bond in 1F5V-13 between A@His215 and B@Ser41 with 74.53% occupancy might be the main reason for the decrease of probe fluorescence emission in experiment. Moreover, Probe 16 was rotated by nearly 60 degrees with respect to the position of other probes in protein binding pocket, deforming the protein active pocket, changing the hydrogen bond formation, which leads to the fluorescence performance of 16 with electron donor and electron acceptor groups was superior to other probes in experiment. The deformation of protein active pocket and the formation of intramolecular hydrogen bonds revealed the difference in performance of NTR fluorescent probe at molecular level, which provide theoretical guidance for latter design of fluorescent probes with better performance.

FT-IR and FT-Raman study of p-sulfonatocalix [8]arene

Spectral study indicates that the hydroxyl groups of calixarene are involved in the formation of intramolecular hydrogen bonds which stabilize the conformation of the pleated loop. Spectral characteristics, charge distribution, and reactivity of calix [8]arenes with tert-butyl (TB8) or sulfonate groups (SC8) were determined. From the IR data of SC8 and TB8, it follows that both substances have practically equal strong cooperative H-bonding. The torsion angles characterizing the conformation of the TB8 and SC8 molecules change.For the SC8 molecule, the pleated loop conformation is by 8.3 kcal/mol more stable than the double cone conformation. The substitution of tert-butyl groups for sulfonyl groups in calixarenes is accompanied by an increase in ionization energy, electronic affinity, chemical potential and dipole moment.

Ab initio investigation of excited state dual hydrogen bonding interactions and proton transfer mechanism for novel oxazoline compound**Project supported by the National Natural Science Foundation of China (Grant No. 11404112), the Funding Scheme for Young Teachers in Colleges and Universities in Henan Province, China (Grant No. 2017GGJS077), and the Key Scientific Research Project of Colleges and Universities of Henan Province,

Owing to the importance of excited state dynamical relaxation, the excited state intramolecular proton transfer (ESIPT) mechanism for a novel compound containing dual hydrogen bond (abbreviated as “1-enol”) is studied in this work. Using density functional theory (DFT) and time-dependent density functional theory (TDDFT) method, the experimental electronic spectra can be reproduced for 1-enol compound. We first verify the formation of dual intramolecular hydrogen bonds, and then confirm that the dual hydrogen bond should be strengthened in the first excited state. The photo-excitation process is analyzed by using frontier molecular orbital (HOMO and LUMO) for 1-enol compound. The obvious intramolecular charge transfer (ICT) provides the driving force to effectively facilitate the ESIPT process in the S1 state. Exploration of the constructed S0-state and S1-state potential energy surface (PES) reveals that only the excited state intramolecular single proton transfer occurs for 1-enol system, which makes up for the deficiencies in previous experiment.

Theoretical insights into excited‐state process for the novel 2,3‐bis[(4‐diethylamino‐2‐hydroxybenzylidene)amino]but‐2‐enedinitrile system

AbstractIn this present work, we clarify the excited‐state intramolecular proton transfer (ESIPT) mechanism for 2,3‐bis[(4‐diethylamino‐2‐hydroxybenzylidene)amino]but‐2‐enedinitrile (BDABE) system. We present the fact that excited‐state single proton transfer can occur along with one hydrogen bond, even though BDABE form consists of two intramolecular hydrogen bonds. Based on the density functional theory and time‐dependent density functional theory methods, we theoretically investigate and elaborate the excited‐state intramolecular dual hydrogen‐bonding interactions. By simulating the electrostatic potential surface, we verify the formation of dual intramolecular hydrogen bonds for BDABE molecule in the S0 state. Furthermore, comparing the primary bond lengths and bond angles as well as the infrared vibrational spectra, we find that the double hydrogen bonds should be strengthened in the S1 state. When it comes to photoexcitation process, we discover the charge redistribution around hydrogen bonding moieties. The increased electronic density around proton acceptor plays the important roles in strengthening hydrogen bonds and in facilitating ESIPT reaction. In view of the possible ESIPT reaction paths (i.e., stepwise and synchronization double proton transfer) for BDABE molecule, we explored the S0‐state and S1‐state potential energy curves. This work explains experimental results and further clarifies the excited‐state behaviors for BDABE system.

Molecular Investigations of the Newly Synthesized Azomethines as Antioxidants: Theoretical and Experimental Studies.

In this study, the antioxidant property of new synthesized azomethins has been investigated as theoretical and experimental. Density functional theory (DFT) was employed to investigate the Bond Dissociation Enthalpy (BDE), Mulliken Charges, NBO analysis, Ionization Potential (IP), Electron Affinities (EA), HOMO and LUMO energies, Hardness (η), Softness (S), Electronegativity (µ), Electrophilic Index (ω), Electron Donating Power (ω-), Electron Accepting Power (ω+) and Energy Gap (Eg) in order to deduce scavenging action of the two new synthesized azomethines (FD-1 and FD-2). Spin density calculations and NBO analysis were also carried out to understand the antioxidant activity mechanism. Comparison of BDE of FD-1 and FD-2 indicate the weal antioxidant potential of these structures. FD-1 and FD-2 have very high antioxidant potential due to the planarity and formation of intramolecular hydrogen bonds.