Intramolecular H-bonding Interactions Research Articles

Folding and duplex formation in mixed sequence recognition-encoded m-phenylene ethynylene polymers.

Oligomers equipped with complementary recognition units have the potential to encode and express chemical information in the same way as nucleic acids. The supramolecular assembly properties of m-phenylene ethynylene polymers equipped with H-bond donor (D = phenol) and H-bond acceptor (A = phosphine oxide) side chains have been investigated in chloroform solution. Polymerisation of a bifunctional monomer in the presence of a monofunctional chain stopper was used for the one pot synthesis of families of m-phenylene ethynylene polymers with sequences ADnA or DAnD (n = 1–5), which were separated by chromatography. All of the oligomers self-associate due to intermolecular H-bonding interactions, but intramolecular folding of the monomeric single strands can be studied in dilute solution. NMR and fluorescence spectroscopy show that the 3-mers ADA and DAD do not fold, but there are intramolecular H-bonding interactions for all of the longer sequences. Nevertheless, 1 : 1 mixtures of sequence complementary oligomers all form stable duplexes. Duplex stability was quantified using DMSO denaturation experiments, which show that the association constant for duplex formation increases by an order of magnitude for every base-pairing interaction added to the chain, from 103 M−1 for ADA·DAD to 105 M−1 for ADDDA·DAAAD. Intramolecular folding is the major pathway that competes with duplex formation between recognition-encoded oligomers and limits the fidelity of sequence-selective assembly. The experimental approach described here provides a practical strategy for rapid evaluation of suitability for the development of programmable synthetic polymers.

Synthesis, characterization, and theoretical studies of the photovoltaic properties of novel reactive azonitrobenzaldehyde derivatives.

All dyes conduct but at different degrees of absorption; it is interesting to study the degree of conductivity and absorptivity of novel reactive azo-dyes in respect to dye-sensitized solar cells (DSSCs) to ascertain their viability for such applications. In this study, four novel reactive azo-dyes were experimentally synthesized from p-aminobenzaldehyde, 4-amino-3-nitrobenzaldehyde, and aniline through series of condensation and coupling reactions. The various functional groups, molecular connectivities, and molecular weight of the various fragments of the synthesized dyes were elucidated using the GC-MS, FT-IR, UV-vis, and NMR respectively. The experimentally determined structures were modeled and investigated using density functional theory (DFT) and time-dependent density functional theory (TD-DFT) approaches to computationally compute the electronic structure properties, reactivity, absorption and solvatochromism in four different phases: gas, ethanol, acetone, and water, and the photovoltaic properties for possible applications in dye-sensitized solar cells (DSSCs). By comparing the HOMO (EH) and the LUMO (EL) energies from the results obtained demonstrates that dye D has the highest EL energy value of −2.48 eV with a relatively lowest EH energy value of −5.63 eV such that it lies underneath the conduction band edge of TiO2 which is necessary to enable charge regeneration. Pi-electron delocalization was observed from the natural bond orbital (NBO) calculations between the different aromatic rings with dye B and A having the relatively highest and least second-order stabilization energies between σ* → σ* and LP* → LP interacting orbitals respectively. It is also observed in all the solvents that the Gibbs free energy of injection (ΔGinject) is greater than 0.2 eV and hence, all the studied azo structures in the four phases provided efficient electron injection and light harvesting efficiency (LHE), however, the value of ΔGinject for dyes B and D is greatest in all the four phases and thus, provided the highest electron injection of all the dyes. From the fact-findings of quantum theory of atoms-in-molecules (QTAIM), dyes A and C have extra-stability due to their relatively high numbers of intramolecular H-bond interactions along with some additional intra-atomic bonding between atoms within the studied compounds. Hence, all the four dyes are good for DSSCs applications.

Stereospecific Synthesis of Cyclic Sulfite Esters with Sulfur-Centered Chirality via Diastereoselective Strategy and Intramolecular H-Bonding Assistance.

Stereospecific synthesis of several cyclic sulfite esters containing three stereogenic centers from enantiopure 1,1,4,4-tetraarylbutanetetraols was achieved. Chiral sulfur centers were constructed stereospecifically via a diastereoselective reaction with the assistance of an intramolecular H-bonding interaction. The absolute configuration of the S atom was elucidated by using the corresponding single-crystal X-ray diffraction analysis of the synthesized monochloride cyclic sulfite esters. Furthermore, a crystallographic evidence of the specific intramolecular C(sp3)-H···CAr weak H-bondings was presented, and its dramatic effect on the 1H NMR spectral properties was revealed. This intriguing behavior was unambiguously rationalized by different shielding effects of the neighboring phenyl rings. Additionally, the theoretical results obtained on the basis of MP2 calculations fully supported the existence of intramolecular hydrogen bonding interactions being responsible for the observed unique chemical and spectral properties.

Design and Optimization of an Acyclic Amine Series of TRPV4 Antagonists by Electronic Modulation of Hydrogen Bond Interactions

Investigation of TRPV4 as a potential target for the treatment of pulmonary edema associated with heart failure generated a novel series of acyclic amine inhibitors displaying exceptional potency and PK properties. The series arose through a scaffold hopping approach, which relied on use of an internal H-bond to replace a saturated heterocyclic ring. Optimization of the lead through investigation of both aryl regions revealed approaches to increase potency through substituents believed to enhance separate intramolecular and intermolecular H-bond interactions. A proposed internal H-bond between the amine and neighboring benzenesulfonamide was stabilized by electronically modulating the benzenesulfonamide. In the aryl ether moiety, substituents para to the nitrile demonstrated an electronic effect on TRPV4 recognition. Finally, the acyclic amines inactivated CYP3A4 and this liability was addressed by modifications that sterically preclude formation of a putative metabolic intermediate complex to deliver advanced TRPV4 antagonists as leads for discovery of novel medicines.

Studies on the structure and conformational flexibility of secondary structures in amyloid beta — A quantum chemical study

Density functional theory (DFT) calculations are performed to study the conformational flexibility of secondary structures in amyloid beta (A[Formula: see text]) polypeptide. In DFT, M06-2X/6-31[Formula: see text]G(d, p) method is used to optimize the secondary structures of 2LFM and 2BEG in gas phase and in solution phase. Our calculations show that the secondary structures are energetically more stable in solution phase than in gas phase. This is due to the presence of strong solvent interaction with the secondary structures considered in this study. Among the backbone [Formula: see text] and [Formula: see text] dihedral angles, [Formula: see text] varies significantly in sheet structure. This is due to the absence of intermolecular hydrogen bond (H-bond) interactions in sheets considered in this study. Our calculations show that the conformational transition of helix/coil to sheet or vice-versa is due to the floppiness of the amino acid residues. This is observed from the Ramachandran map of the studied secondary structures. Further, it is noted that the intramolecular H-bond interactions play a significant role in the conformational transition of secondary structures of A[Formula: see text].

Mercury (II) sensing via cyclization of a dithioamide into a benzimidazole derivative: A structural and spectroscopic study

An o-phenylenediamine-derived dithioamide L was found to sense Hg(II) in the UV–visible via Hg(II)-mediated cyclization leading to a new benzimidazole derivative (L′). Both L and L′ have been characterized by single-crystal X-ray crystallography. The structure of L reveals relatively strong intramolecular H-bonding interactions of NH...S type. The extended structure is consolidated by several classical hydrogen bonding interactions. For L′, analysis of the packing pattern reveals few non-classical H-bonding contacts. Spectroscopic studies by FT-IR, UV–Visible, 1H-and 13C NMR support the single-crystal X-ray crystallography results and confirm the formation of the new benzimidazole derivative. UV–Vis titrations suggest and NMR confirms that the cyclization reaction occurs via an initial formation of a Hg(II) complex, which is too transient to be fully characterized. As this reaction is Hg(II)-mediated, dithioamide L acts as a selective Hg(II) sensor as shown by UV–Visible titrations and a selectivity study against Pb(II), Cd(II), Ca(II), Zn(II), Ag(I), and Cr(III): For Hg(II), but not for other metals, a distinct color change from yellow to pink is observed with corresponding UV–Vis spectroscopic changes and an isosbestic point at 270 nm.

Living Supramolecular Polymerization of an Aza-BODIPY Dye Controlled by a Hydrogen-Bond-Accepting Triazole Unit Introduced by Click Chemistry.

An aza-BODIPY dye 1 bearing two hydrophobic fan-shaped tridodecyloxybenzamide pendants through 1,2,3-triazole linkages was synthesized by a click reaction and characterized. 1 H NMR studies indicated that dye 1 exhibited variable conformations through intramolecular H-bonding interaction, which is beneficial for the polymorphism of aggregation. The thermodynamic, structural, and kinetic aspect of the supramolecular polymerization of dye 1 was investigated by UV/Vis absorption spectroscopy, IR spectroscopy, AFM, TEM, and SEM. Biphasic aggregation pathways of dye 1, leads to the formation of off-pathway, metastable Agg. I and thermodynamically stable Agg. II with distinct H-aggregation spectra and nanoscale morphology. The living manner of the supramolecular polymerization of dye 1 was demonstrated in seeded polymerization experiments with temperature-modulated successive cooling-heating cycles.

Syntheses and X-ray crystal structures combined with conformational and Hirshfeld analyses of chalcones based on a cyclohexanone scaffold

Four chalcone structures based on cyclohexanone cores were presented. The structures of bis-benzylidenecyclohexanone analogs 3a-d were elucidated using spectrophotometric and single-crystal X-ray techniques. Compounds 3a, 3b, and 3d crystalized in the monoclinic crystal system with the space group P21/c. However, 3c crystalized in the orthorhombic system with the space group Pna21. A set of computational studies related to the structures were carried out. Using the B3LYP method and the 6-31G(d,p) basis set, the molecular structures of the studied dienones were optimized, followed by the evaluation of their electronic properties and UV–vis spectra. The bond distances and angles well-correlated with the experimental data. All the dienones were stabilized by C–H⋯O intramolecular H-bonding interactions. The presence of two Cl atoms at the ortho-position of each phenyl ring in 3c caused steric hinderance with the cyclohexanone ring, leading to the weakest H⋯O interactions among the studied compounds. The TD-DFT method was used to assign and explain the origin of the electronic spectra of the studied dienones.

Elucidating cylindrospermopsin toxicity via synthetic analogues: An in vitro approach

Cylindrospermopsin (CYN) is an alkaloid biosynthesized by selected cyanobacteria, the cyto- and genotoxic properties of which have been studied extensively by in vitro and in vivo experimental models. Various studies have separately established the role of uracil, guanidine and hydroxyl groups in CYN-induced toxicity. In the present study, we have prepared five synthetic analogues that all possess a uracil group but had variations in the other functionality found in CYN. We compared the in vitro toxicity of these analogues in common carp hepatocytes by assessing oxidative stress markers, DNA fragmentation and apoptosis. All the analogues tested induced generation of reactive oxygen species, lipid peroxidation (LPO) and DNA fragmentation. However, the greatest increase in LPO and increase in caspase-3 activity, an apoptosis marker, was demonstrated by an analogue containing guanidine, hydroxyl and uracil functionalities similar to those found in CYN but lacking the complex tricyclic structure of CYN. We also report a crystal structure of an analogue lacking the hydroxyl group found in CYN which does not show intramolecular H-bonding interactions between the guanidine and the uracil functionalities. The observations made in this work supports the hypothesis that CYN toxicity is a result of an interplay between both of the uracil, hydroxyl and guanidine functional groups.

Tunable intramolecular multicenter H-bonding interactions in first-row metal complexes bearing bidentate redox-active ligands

In this research article, we report the synthesis and structural characterization of a family of first-row metal complexes bearing redox-active ligands with tunable H-bonding donors. We observed that these coordination complexes can adopt three different geometries and that they are stabilized by intramolecular multicenter H-bonding interactions, which are systematically modified by changing the metal ion (Co, Ni, Cu, Zn), the ligand scaffold (variations in the diamine and ureanyl substituents used) and the solvent of crystallization.

Catalytic Aerobic Oxidation of Alcohols by Copper Complexes Bearing Redox-Active Ligands with Tunable H-Bonding Groups.

In this research article, we describe the structure, spectroscopy, and reactivity of a family of copper complexes bearing bidentate redox-active ligands that contain H-bonding donor groups. Single-crystal X-ray crystallography shows that these tetracoordinate complexes are stabilized by intramolecular H-bonding interactions between the two ligand scaffolds. Interestingly, the Cu complexes undergo multiple reversible oxidation-reduction processes associated with the metal ion (CuI, CuII, CuIII) and/or the o-phenyldiamido ligand (L2-, L•-, L). Moreover, some of the CuII complexes catalyze the aerobic oxidation of alcohols to aldehydes (or ketones) at room temperature. Our extensive mechanistic analysis suggests that the dehydrogenation of alcohols occurs via an unusual reaction pathway for galactose oxidase model systems, in which O2 reduction occurs concurrently with substrate oxidation.

Effect of H-bond and molecular geometry towards innocent and non-innocent behavior of 3,5-di-tert-butyl-2-aminophenol units attached to a piperazine backbone: Co(III) and Cu(II) complexes

A 2-aminophenol-based potential non-innocent ligand H4L have been synthesized by reacting 2,2′-(piperazine-1,4-diylbis(methylene))dianiline with 2.0 equivalent amounts of 3,5-di-tert-butyl-catechol. In the ligand, both 2-aminophenol units were connected by a piperazine unit. X-ray single crystal analysis of ligand H4L revealed that piperazine unit was present in the more stable chair conformation. The ligand provided six-coordinate, mononuclear, diamagnetic complex 1 {[CoIII(H2L)]Cl} upon reacting with CoCl2·6H2O. A binuclear biradical-containing complex 2 {[CuII2(L)Cl2]} was obtained by reacting ligand H4L with 2.0 equivalent amounts of CuCl2·2H2O. Both the complexes were characterized by using IR, mass, UV–Vis/NIR, and single crystal X-ray crystallographic techniques. X-ray crystallographic analysis revealed that in complex 1 the ligand unit retained its oxidation state, while one-electron oxidation of each 2-aminophenol unit to 2-iminosemiquinone unit was noticed in case of complex 2. Two strong intramolecular H-bond interactions were found to be responsible for the innocent character of the 2-aminophenol coordination units in complex 1. Herein, the boat conformation of the piperazine backbone and the octahedral geometry of the complex promoted the interactions. The ligand, upon reacted with an equivalent amount of Cu(ClO4)2·6H2O in the presence of Et3N under air in CH3CN, provided a green solid (complex 3). Spectroscopic characterization, and DFT–based computational study indicated that the green solid was a four-coordinate, mononuclear, paramagnetic Cu(II) complex {3; [CuII(L)]} with two coordinated iminosemiquinone radicals. The optimized structure revealed that the piperazine unit in the complex was in the boat conformation.

Desulfurization of coal using four ionic liquids with [HSO4

Sulfur dioxide produced from Coal-fire power plant are the main sources of air pollution and PM2.5 (the aerodynamic diameter less than or equal to 2.5 μm) which may result in multiple short term and long term health impacts. In this investigation, four ionic liquids, i.e. 1-butyl-3-methyl imidazolium bisulfate([C4C1im][HSO4]), 1-carboxymethyl-3-methylimidazolium bisulfate([HOOCCH2mim][HSO4]), N-butylpyridinium bisulfate([C4Py][HSO4]) and 1-carboxymethyl-3-methylpyridinium bisulfate([HOOCCH2Py][HSO4]), were used to remove sulfur from coal combining with 30% hydrogen peroxide (H2O2) based on chemically oxidative desulfurization. The experimental results of FTIR and XPS indicate that ionic liquids could enhance the oxidation of organic sulfur in H2O2, where [HOOCCH2mim][HSO4]-H2O2 solution can remove 16.76% of organic sulfur, much better than the single 30% H2O2 aqueous solution. Generally, imidazolium ionic liquids are more favorable for organic sulfur removal compared to pyridinium ones. Carboxyl group tethered on imidazolium cation could improve the oxidability of H2O2 due to the formation of peroxycarboxylic acid group. The stronger intramolecular H-bonding interaction of pyridinium ionic liquids is the structural reason for their relatively weak sulfur removal ability.

The role of chlorine substituents in lichexanthones properties: the ionic and halogen bond interactions

The effects of chlorine substituents (Cl substituents) on the structural and electronic properties of lichexanthones (LXs) such as aromaticity of rings, the intramolecular interactions and the complexation of LXs with Mg2+ and NH3 (the ionic and halogen bond interactions) have been investigated by the quantum mechanical calculations at the M06-2X/6-311++G(d,p) level of theory. The effects of Cl substituents on the intramolecular H-bond interactions strongly depend on their positions on the ring. The Cl substituents increase the E2 values of nX → π*CC interactions, obtained from the natural bond orbital analysis, reduce the electron densities on the center of the substituted ring, ρRCP in the results of atoms in molecules analysis, and decrease the aromaticity of the rings with respect to the aromatic fluctuation index. The stabilities of compounds depend on the aromaticity of rings, the O···H-bond strength, and especially the Cl···H interaction. Also, the effects of substituents on the local minimum values of electrostatic potential around the O atoms (Vmin) and therefore the binding energies of [LX···Mg]2+ and [LX···Mg·4H2O]2+ complexes strongly depend on the positions of the substituents. The aromaticity of rings A and C decrease and that of B increases after complexation with the Mg2+ ion. The electronic effects (and in some cases the steric effects) play a special role in the formation and stability of LX···NH3 complexes. The stabilities of the LX···NH3 complexes increase by increasing the natural charges and the local maximum electrostatic potential (Vmax−Cl) calculated, respectively, on and around the Cl atoms, and the ρCl−N values calculated at the Cl···N BCPs.

New hybrid of the barbituric acid motif: synthesis, X-ray single crystal, DFT, and Hirshfeld surface analyses

A one-pot multi-component reaction of N,N-dimethylbarbituric acid,1,3-cyclohexanedione and 3-bromobenzaldehyde in H2O mediated by diethyl amine as a base affords a new barbituric acid–cyclohexanedione hybrid. The reaction proceeds smoothly, efficiently, and in high yield. The molecular structure of this compound was determined by single-crystal X-ray diffraction crystallography and spectrophotometric analyses. Of the nine possible isomers of the studied compound, the B3LYP/6-31G(d,p) method predicts that form B, in which the two OH groups are involved in significant intramolecular H-bonding interactions with the neighboring carbonyl O atom, is the most stable form in the gas phase. The X-ray structure reveals a different isomer due to intermolecular interactions caused by molecular packing in the crystal, which stabilizes the solid-state structure. Hirshfeld surface analysis of the molecular packing indicates that the H···O interactions are the primary contributor (24.5%) to the intermolecular stabilization in the crystal.

The physicochemical properties and tyrosinase inhibitory activity of ectoine and its analogues: A theoretical study

Abstract Protonation, deprotonation, and proton transfer were considered in ectoine (ECT) and some of its derivatives in the gas phase and solution media by the quantum mechanical calculations. The results of present study help to understand the activity of mentioned compounds as osmolytes, which are also important in water activity and osmotic pressure within a cell. Proton diffuses through the water solvent, covers the distance between the acidic and basic groups, and leads to the protonation of basic group. The deprotonation of NH group is often easier than COOH, because of intramolecular H-bond interactions in the anionic forms. The protonation of N atom is easier than the deprotonation of COOH and NH groups in all compounds with respect to the energy data, results of atoms in molecules (AIM), and molecular electrostatic potential (MEP) analyses. The proton transfer from NH to N is favorable in solution media, acidic and basic environments which is in agreement with the high tendency of NH group and N atom in deprotonation and protonation, respectively. Results indicate that protonation, deprotonation, and proton transfer are almost the same in all compounds and lead to the same biological activities. In addition, the inhibitory activity of compounds on tyrosinase enzyme was studied using the results of molecular docking. The proper orientation of PO 3 H 2 group in the binding pocket causes suitable interactions with HIS244, GLU256, and ASN260 amino acids. Thus, it seems that the highest inhibitory activity corresponds to the compound with the –CH 2 -PO 3 H 2 substituent.

Studies of intramolecular H-bond interactions and solvent effects in the conformers of glycolic acid — A quantum chemical study

In this work, density functional theory is applied to understand the conformational stability and solvent effects on glycolic acid conformers in different solvents. In addition, the role of intramolecular hydrogen bond (H-bond) interactions in the stability of conformers are investigated. The molecular geometries of selected conformers are optimized using B3LYP and PBE0 functionals with 6-311[Formula: see text]G(d,p) basis set. The effects of solvent on the geometrical parameters, relative stability, dipole moment, chemical hardness, chemical potential, etc. are studied for the conformers of glycolic acid. Our calculations show that the order of stability of the SSC and AAT conformers does not change in liquid phase. However, the energy of SSC and AAT conformers is very close to each other in water media. In water media, strong intramolecular H-bond interaction is present in AAT conformer which causes the energy of AAT conformer to be very close to that of SSC conformer. This may be due to the influence of water media.

Conformational switching via an intramolecular H-bond modulates the fluorescence lifetime in a novel coumarin-imidazole conjugate.

Achieving synthetic control over light-driven molecular dynamics is essential for designing complex molecule-based devices. Here we design a novel coumarin-imidazole conjugate (1) whose excited state structural dynamics are primarily controlled by a distant intramolecular H-bonding interaction within the backbone. The coumarin conjugate is based on a 1,2,4,5-aryl substituted imidazole framework (aryl = -Ph and -PhOH) covalently connected to the coumarin moiety via a C-N bond. A carefully positioned OH group in the aryl part of the imidazole fragment resulted in achieving two dissimilar O-HN and O-HO distal intramolecular hydrogen bonding interactions. NMR studies in conjunction with density functional theory (DFT) at the B3LYP/6-311G(d,p) level of theory show the existence of two ground state conformers with a rotational barrier of 6.12 kcal mol-1. Due to the presence of conformational isomers of 1, the local excited state dynamics of the parent coumarin get biased towards a long-lived fluorescence state with diminished non-radiative decay channels. Time-resolved emission studies show an ∼4-5 times increase in the excited state lifetime in 1 when compared to coumarin-imidazole conjugates, 2 and 3, without the OH group. Solvent dependent studies show that solvent polarity, the H-bond donating ability and viscosity dictate the conformational distribution in the ground state and the dynamical evolution to the final emissive state. Our studies highlight the importance of rotamerism around the C1-C4 single bond, which leads to rigidification along the coumarin-imidazole backbone through a combination of distal H-bonding and solvent interactions. The concept of new emission signaling pathways caused by conformational switching between two states offers a new paradigm to introduce functional allostery in macromolecular backbones.

A supramolecular approach to the examination of the structures of some anticancer organoamidoplatinum(II) complexes

A range of supramolecular interactions revealed on assessment of crystal packing of the previously reported organoamidoplatinum(II) complexes, [Pt{(p-BrC6F4)NCH2CH2NEt2}(py)Cl], 1; [Pt{(p-HC6F4)NCH2CH2NEt2}(py)Cl], 2; [Pt{(C6F5)NCH2CH2NEt2}(py)I], 3; [Pt{(p-HC6F4)NCH2CH2NMe2}Cl(py)], 4; [Pt{(C6F5)NCH2CH2NMe2}Cl0.4I0.6(py)], 5 is examined. These interactions frequently include the axial positions above and below the coordination planes. Agostic interactions, inter- and intra-molecular H-bonding and other supramolecular interactions of all compounds were explored for a better understanding of solid state structural properties. This propensity to form a range of supramolecular interactions may assist in docking the drugs to DNA prior to coordination of DNA to these compounds.

A New Design Strategy for Efficient Thermally Activated Delayed Fluorescence Organic Emitters: From Twisted to Planar Structures.

In the traditional molecular design of thermally activated delayed fluorescence (TADF) emitters composed of electron-donor and electron-acceptor moieties, achieving a small singlet-triplet energy gap (ΔEST ) in strongly twisted structures usually translates into a small fluorescence oscillator strength, which can significantly decrease the emission quantum yield and limit efficiency in organic light-emitting diode devices. Here, based on the results of quantum-chemical calculations on TADF emitters composed of carbazole donor and 2,4,6-triphenyl-1,3,5-triazine acceptor moieties, a new strategy is proposed for the molecular design of efficient TADF emitters that combine a small ΔEST with a large fluorescence oscillator strength. Since this strategy goes beyond the traditional framework of structurally twisted, charge-transfer type emitters, importantly, it opens the way for coplanar molecules to be efficient TADF emitters. Here, a new emitter, composed of azatriangulene and diphenyltriazine moieties, is theoretically designed, which is coplanar due to intramolecular H-bonding interactions. The synthesis of this hexamethylazatriangulene-triazine (HMAT-TRZ) emitter and its preliminary photophysical characterizations point to HMAT-TRZ as a potential efficient TADF emitter.