Bis(Dicarbollide) Complexes of Transition Metals: How Substituents in Dicarbollide Ligands Affect the Geometry and Properties of the Complexes.

The interaction between different types of substituents in dicarbollide ligands and their influence on the stabilization of various rotational conformers (rotamers) of transition metal bis(dicarbollide) complexes [3,3'-M(1,2-C2B9H11)2]- are considered. It has been shown that the formation of intramolecular CH···X hydrogen bonds between dicarbollide ligands is determined by the size of the proton acceptor atom X rather than its electronegativity. Due to the stabilization of rotamers with different dipole moments, intramolecular hydrogen bonds between ligands in transition metal bis(dicarbollide) complexes can have a significant impact on the biological properties of their derivatives. In the presence of external complexing metals, weak intramolecular CH···X hydrogen bonds can be broken to form stronger X->M donor-acceptor bonds. This process is accompanied by the mutual rotation of dicarbollide ligands and can be used in sensors and molecular switches based on transition metal bis(dicarbollide) complexes.

Crystalline Porous Organic Cage Membranes Constructed Using Fortified Intermolecular Interactions for Molecular Sieving.

Among the various types of materials with intrinsic porosity, porous organic cages (POCs) are distinctive as discrete molecules that possess intrinsic cavities and extrinsic channels capable of facilitating molecular sieving. However, the fabrication of POC membranes remains highly challenging due to the weak noncovalent intermolecular interactions and most reported POCs are powders. In this study, we constructed crystalline free-standing porous organic cage membranes by fortifying intermolecular interactions through the induction of intramolecular hydrogen bonds, which was confirmed by single-crystal X-ray analysis. To elucidate the driving forces behind, a series of terephthaldehyde building blocks containing different substitutions were reacted with flexible triamine under different conditions via interfacial polymerization (IP). Furthermore, density functional theory (DFT) calculations suggest that intramolecular hydrogen bonding can significantly boost the intermolecular interactions. The resulting membranes exhibited fast solvent permeance and high rejection of dyes not only in water, but also in organic solvents. In addition, the membrane demonstrated excellent performance in precise molecular sieving in organic solvents. This work opens an avenue to designing and fabricating free-standing membranes composed of porous organic materials for efficient molecular sieving.

The Effect of Intramolecular Hydrogen Bonds on the Rotational Barriers of the Biaryl C-C Axis.

Axially chiral compounds are attracting more attention recently. Although hydrogen bonds are reported as a vital weak force that influences the properties of compounds, the effect of intramolecular hydrogen bonds on the atropisomerization of the Caryl -Caryl single bonds has not yet been well quantitatively investigated. Here, a series of axially chiral biaryl compounds were synthesized to study the effect of hydrogen bonds on the rotational barriers of the biaryl C-C axis. Experimental studies demonstrated that the rotational barrier of hydrogen bonding biaryl 9 was significantly lower (46.7 kJ mol-1 ) than biaryl 10 without hydrogen bonds. Furthermore, theoretical studies revealed that the intramolecular hydrogen bond stabilized the transition state (TS) of tri-ortho-substituted biaryl 9, relieving the steric repulsion in the TS. We believe that this study will provide chemists with a deeper understanding of the atropisomerization process of axially chiral biaryl compounds.

Molecular Dynamics Study of Clathrate-like Ordering of Water in Supersaturated Methane Solution at Low Pressure.

Using molecular dynamics, the evolution of a metastable solution for "methane + water" was studied for concentrations of 3.36, 6.5, 9.45, 12.2, and 14.8 mol% methane at 270 K and 1 bar during 100 ns. We have found the intriguing behavior of the system containing over 10,000 water molecules: the formation of hydrate-like structures is observed at 6.5 and 9.45 mol% concentrations throughout the entire solution volume. This formation of "blobs" and the following amorphous hydrate were studied. The creation of a metastable methane solution through supersaturation is the key to triggering the collective process of hydrate formation under low pressure. Even the first stage (0-1 ns), before the first fluctuating cavities appear, is a collective process of H-bond network reorganization. The formation of fluctuation cavities appears before steady hydrate growth begins and is associated with a preceding uniform increase in the water molecule's tetrahedrality. Later, the constantly presented hydrate cavities become the foundation for a few independent hydrate nucleation centers, this evolution is consistent with the labile cluster and local structure hypotheses. This new mechanism of hydrogen-bond network reorganization depends on the entropy of the cavity arrangement of the guest molecules in the hydrate lattice and leads to hydrate growth.

Photobase-Driven Excited-State Intramolecular Proton Transfer (ESIPT) in a Strapped π-Electron System.

We report a new design strategy for an excited-state intramolecular proton transfer (ESIPT) fluorophore that can be used in acidic media. A photobasic pyridine-centered donor-acceptor-donor-type fluorophore is combined with a basic trialkylamine "strap". In the presence of an acid, protonation occurs predominantly at the amine moiety in the ground state. A single-crystal X-ray diffraction analysis confirmed the formation of a pre-organized intramolecular hydrogen-bonded structure between the resulting ammonium moiety and the pyridine ring. Upon excitation, the intramolecular charge-transfer transition increases the basicity of the pyridine moiety in the excited state, resulting in proton transfer from the amine to the pyridine moiety. Consequently, the fluorophore takes on a polymethine-dye character in the ESIPT state, which gives rise to significantly red-shifted emission with an increased fluorescence quantum yield.

Managing Experimental 3D Structures in the Beyond-Rule-of-5 Chemical Space: The Case of Rifampicin.

The beyond-Rule-of-5 (bRo5) chemical space is a source of new oral drugs and includes large and flexible compounds. Because of their size and conformational variability, bRo5 molecules assume different privileged conformations in the compartments of human body, i. e., they can exhibit chameleonic properties. The elucidation of the ensemble of 3D structures explored by such molecules under different conditions is therefore critical to check the role played by chameleonicity to modulate cell permeability. Here we characterized the conformational ensembles of rifampicin, a bRo5 drug, in polar and nonpolar solvents and in the solid state. We performed NMR experiments, analyzed their results with a novel algorithm and set-up a pool of ad hoc in silico strategies to investigate crystallographic structures retrieved from the CSD. Moreover, a polarity descriptor often related to permeability (SA-3D-PSA) was calculated for all the conformers and its variation with the environment analyzed. Results showed that the conformational behavior of rifampicin in solution and in the solid state is not superposable. The identification of dynamic intramolecular hydrogen bonds can be assessed by NMR spectroscopy but not by X-ray structures. Moreover, SA-3D-PSA revealed that dynamic IMHBs do not provide rifampicin with chameleonic properties. Overall, this study highlights that the peculiarity of rifampicin, which is cell permeable probably because of the presence of static IMHBs but is devoid of any chameleonic behavior, can be assessed by a proper analysis of experimental 3D structures.

Perturbating Intramolecular Hydrogen Bonds through Substituent Effects or Non-Covalent Interactions.

An analysis of the effects induced by F, Cl, and Br-substituents at the α-position of both, the hydroxyl or the amino group for a series of amino-alcohols, HOCH2(CH2)nCH2NH2 (n = 0-5) on the strength and characteristics of their OH···N or NH···O intramolecular hydrogen bonds (IMHBs) was carried out through the use of high-level G4 ab initio calculations. For the parent unsubstituted amino-alcohols, it is found that the strength of the OH···N IMHB goes through a maximum for n = 2, as revealed by the use of appropriate isodesmic reactions, natural bond orbital (NBO) analysis and atoms in molecules (AIM), and non-covalent interaction (NCI) procedures. The corresponding infrared (IR) spectra also reflect the same trends. When the α-position to the hydroxyl group is substituted by halogen atoms, the OH···N IMHB significantly reinforces following the trend H < F < Cl < Br. Conversely, when the substitution takes place at the α-position with respect to the amino group, the result is a weakening of the OH···N IMHB. A totally different scenario is found when the amino-alcohols HOCH2(CH2)nCH2NH2 (n = 0-3) interact with BeF2. Although the presence of the beryllium derivative dramatically increases the strength of the IMHBs, the possibility for the beryllium atom to interact simultaneously with the O and the N atoms of the amino-alcohol leads to the global minimum of the potential energy surface, with the result that the IMHBs are replaced by two beryllium bonds.

Synthesis of 3-Aryl-ortho-carboranes with Sensitive Functional Groups.

A simple and efficient method was developed for the one-pot synthesis of 3-aryl derivatives of ortho-carborane with sensitive functional groups using 3-iodo-ortho-carborane and aryl zinc bromides that were generated in situ. A series of 3-aryl-ortho-carboranes, including those containing nitrile and ester groups, 3-RC6H4-1,2-C2B10H11 (R = p-Me, p-NMe2, p-OCH2OMe, p-OMe, o-CN, p-CN, o-COOEt, m-COOEt, p-COOEt) was synthesized using this approach. The solid-state structures of 3-RC6H4-1,2-C2B10H11 (R = p-OMe, o-CN, and p-CN) were determined by single crystal X-ray diffraction. The intramolecular hydrogen bonding involving the ortho-substituents of the aryl ring and the CH and BH groups of carborane was discussed.

A Spectroscopic Overview of Intramolecular Hydrogen Bonds of NH O,S,N Type.

Intramolecular NH…O,S,N interactions in non-tautomeric systems are reviewed in a broad range of compounds covering a variety of NH donors and hydrogen bond acceptors. 1H chemical shifts of NH donors are good tools to study intramolecular hydrogen bonding. However in some cases they have to be corrected for ring current effects. Deuterium isotope effects on 13C and 15N chemical shifts and primary isotope effects are usually used to judge the strength of hydrogen bonds. Primary isotope effects are investigated in a new range of magnitudes. Isotope ratios of NH stretching frequencies, νNH/ND, are revisited. Hydrogen bond energies are reviewed and two-bond deuterium isotope effects on 13C chemical shifts are investigated as a possible means of estimating hydrogen bond energies.

Perturbing the O-H O Hydrogen Bond in 1-oxo-3-hydroxy-2-propene.

Ab initio MP2/aug'-cc-pVTZ calculations have been carried out to identify and characterize equilibrium structures and transition structures on the 1-oxo-3-hydroxy-2-propene: Lewis acid potential energy surfaces, with the acids LiH, LiF, BeH2, and BeF2. Two equilibrium structures, one with the acid interacting with the C=O group and the other with the interaction occurring at the O-H group, exist on all surfaces. These structures are separated by transition structures that present the barriers to the interconversion of the two equilibrium structures. The structures with the acid interacting at the C=O group have the greater binding energies. Since the barriers to convert the structures with interaction occurring at the O-H group are small, only the isomers with interaction occurring at the C=O group could be experimentally observed, even at low temperatures. Charge-transfer energies were computed for equilibrium structures, and EOM-CCSD spin-spin coupling constants 2hJ(O-O), 1hJ(H-O), and 1J(O-H) were computed for equilibrium and transition structures. These coupling constants exhibit a second-order dependence on the corresponding distances, with very high correlation coefficients.

Naphthazarin Derivatives in the Light of Intra- and Intermolecular Forces.

Our long-term investigations have been devoted the characterization of intramolecular hydrogen bonds in cyclic compounds. Our previous work covers naphthazarin, the parent compound of two systems discussed in the current work: 2,3-dimethylnaphthazarin (1) and 2,3-dimethoxy-6-methylnaphthazarin (2). Intramolecular hydrogen bonds and substituent effects in these compounds were analyzed on the basis of Density Functional Theory (DFT), Møller-Plesset second-order perturbation theory (MP2), Coupled Clusters with Singles and Doubles (CCSD) and Car-Parrinello Molecular Dynamics (CPMD). The simulations were carried out in the gas and crystalline phases. The nuclear quantum effects were incorporated a posteriori using the snapshots taken from ab initio trajectories. Further, they were used to solve a vibrational Schrödinger equation. The proton reaction path was studied using B3LYP, ωB97XD and PBE functionals with a 6-311++G(2d,2p) basis set. Two energy minima (deep and shallow) were found, indicating that the proton transfer phenomena could occur in the electronic ground state. Next, the electronic structure and topology were examined in the molecular and proton transferred (PT) forms. The Atoms In Molecules (AIM) theory was employed for this purpose. It was found that the hydrogen bond is stronger in the proton transferred (PT) forms. In order to estimate the dimers' stabilization and forces responsible for it, the Symmetry-Adapted Perturbation Theory (SAPT) was applied. The energy decomposition revealed that dispersion is the primary factor stabilizing the dimeric forms and crystal structure of both compounds. The CPMD results showed that the proton transfer phenomena occurred in both studied compounds, as well as in both phases. In the case of compound 2, the proton transfer events are more frequent in the solid state, indicating an influence of the environmental effects on the bridged proton dynamics. Finally, the vibrational signatures were computed for both compounds using the CPMD trajectories. The Fourier transformation of the autocorrelation function of atomic velocity was applied to obtain the power spectra. The IR spectra show very broad absorption regions between 700 cm-1-1700 cm-1 and 2300 cm-1-3400 cm-1 in the gas phase and 600 cm-1-1800 cm-1 and 2200 cm-1-3400 cm-1 in the solid state for compound 1. The absorption regions for compound 2 were found as follows: 700 cm-1-1700 cm-1 and 2300 cm-1-3300 cm-1 for the gas phase and one broad absorption region in the solid state between 700 cm-1 and 3100 cm-1. The obtained spectroscopic features confirmed a strong mobility of the bridged protons. The inclusion of nuclear quantum effects showed a stronger delocalization of the bridged protons.

S-H O and O-H O Hydrogen Bonds-Comparison of Dimers of Thiocarboxylic and Carboxylic Acids.

ωB97-XD/aug-cc-pVTZ calculations were performed on dimers of selected thiocarboxylic acids and on analogous carboxylic acids. The sample of calculated thiocarboxylic acids is an extension of the Cambridge Structural Database search that contains only a few such structures. The Natural Bond Orbital (NBO) method, Symmetry-Adapted Perturbation Theory (SAPT) approach, Non-Covalent Interaction (NCI) method and Quantum Theory of Atoms in Molecules (QTAIM) were applied additionally to analyse interactions in dimers of thiocarboxylic and carboxylic acids. The insights into crystal structures as well as into results of calculations show that the formation of S-H…O hydrogen bonds between molecules of thiocarboxylic acids is steered by the same mechanisms as the formation of much stronger O-H…O hydrogen bonds in carboxylic acids. The intramolecular O-H…O and C-H…S hydrogen bonds occurring in few considered structures are also analysed.

Perylene Bisimide and Naphthyl-Based Molecular Dyads: Hydrogen Bonds Driving Co-planarization and Anomalous Temperature-Response Fluorescence.

The origin of the positive temperature effect in fluorescence emission of a newly designed perylene bisimide (PBI) derivative with two naphthyl units containing ortho-methoxy group (NM) at its bay positions (PBI-2NM) was elucidated. A key point is the finding of a weak hydrogen bond (<5.0 kcal mol-1 ) between the methoxy group of the NM unit and a nearby hydrogen atom of the PBI core. It is the bonding that drives co-planarization of the different aromatic units, resulting in delocalization of the π-electrons of the compound as synthesized, inducing fluorescence quenching via intramolecular charge transfer (ICT). With increasing temperature, the co-planar structure could be distorted in part, resulting in a decreased degree of ICT, and hence leading to enhanced fluorescence emission. The unique positive temperature effect in emission induced by H-bond-driven co-planarization may pave a new avenue in designing functional molecular systems complementary to conventional methods.

Gas phase basicities of polyfunctional molecules. Part 5: Non-aromatic sp2 nitrogen containing compounds.

This paper constitutes the fifth part of a general review of the gas-phase protonation thermochemistry of polyfunctional molecules (Part 1: Theory and methods, Mass Spectrom Rev 2007, 26:775-835, Part 2: Saturated basic sites, Mass Spectrom Rev 2012, 31:353-390, Part 3: Amino acids, Mass Spectrom Rev 2012, 31:391-435, Part 4: Carbonyl as basic site, Mass Spectrom Rev 2015, 34:493-534). This part is devoted to non-aromatic molecules characterized by a lone pair located on a sp2 nitrogen atom, it embraces functional groups such as imines, amidines, guanidines, diazenes, hydrazines, oximes, and phosphazenes. Specific examples are examined under five major chapters. In the first one, aliphatic and unsaturated (conjugated and cyclic) imines, hydrazones, and oximes are considered. A second chapter describes the protonation energetic of aliphatic, conjugated, or cyclic amidines. Guanidines, polyguanides, and biomolecules containing guanidine were examined in the third chapter. A fourth chapter describes the particular case of the phosphazene molecules. Finally, diazenes and azides were considered in the last chapter. Experimental data were re-evaluated according to the presently adopted basicity scale, i.e., PA(NH3 ) = 853.6 kJ/mol, GB (NH3 ) = 819 kJ/mol. Structural and energetic information given by G4MP2 quantum chemistry computations on typical systems are presented. © 2016 Wiley Periodicals, Inc. Mass Spec Rev 37:139-170, 2018.

Cooperative Effects in Weak Interactions: Enhancement of Tetrel Bonds by Intramolecular Hydrogen Bonds.

A series of silyl and germanium complexes containing halogen atoms (fluorine and chlorine atoms) and exhibiting tetrel bonds with Lewis bases were analyzed by means of Møller-Plesset computational theory. Binding energies of germanium derivatives were more negative than silicon ones. Amongst the different Lewis bases utilized, ammonia produced the strongest tetrel bonded complexes in both Ge and Si cases, and substitution of the F atom by Cl led to stronger complexes with an ethylene backbone. However, with phenyl backbones, the fluorosilyl complexes were shown to be less stable than the chlorosilyl ones, but the opposite occurred for halogermanium complexes. In all the cases studied, the presence of a hydroxyl group enhanced the tetrel bond. That effect becomes more remarkable when an intramolecular hydrogen bond between the halogen and the hydrogen atom of the hydroxyl group takes places.

A strategy of utilizing Zn(II) as metallic pivot in room temperature ionic liquid to prepare molecularly imprinted polymers for compound with intramolecular hydrogen bonds.

A method of preparing molecularly imprinted polymers (MIPs) with Zn(II) as a metallic pivot was adopted to solve the problem of imprinting compound with intramolecular hydrogen bonds by forming stronger coordination binding interaction among the template-functional monomer-Zn2+ complex. A ternary porogenic system including dimethyl sulfoxide, dimethylformamide, and room temperature ionic liquid 1-butyl-3-methylimidazolium tetrafluoroborate was employed to fabricate imprinted monolith with high porosity and good flow-through properties, in which chicoric acid (CA), zinc acetate, 4-vinylpyridine (4-VP), and ethylene glycol dimethacrylate (EDMA) was the template, metallic ion, functional monomer, as well as crosslinker, respectively. The influence of polymerization factors including the 4-VP-CA ratio, monomer-crosslinker ratio, template-Zn2+ ratio on imprinting factors was systematically investigated. When the ratio of 4-VP to CA was 24:1, the greatest IF value (24.81) was achieved on the CA-MIP prepared with zinc acetate. In addition, off-line SPE with the optimal MIPs monolith led to high purity of CA (98.0% ± 0.5%) from extraction of Cichorium intybus L. roots with the recovery of 77.5% ± 2.5% (n = 6). As a conclusion, the strategy of introducing metal ions as metal pivot to prepare MIPs was a powerful method for the MIPs synthesis to the template molecules with intramolecular hydrogen bonds.

Gas-phase basicities of polyfunctional molecules. Part 4: Carbonyl groups as basic sites.

This article constitutes the fourth part of a general review of the gas-phase protonation thermochemistry of polyfunctional molecules (Part 1: Theory and methods, Mass Spectrom Rev 2007, 26:775-835, Part 2: Saturated basic sites, Mass Spectrom Rev 2012, 31:353-390, Part 3: Amino acids, Mass Spectrom Rev 2012, 31:391-435). This fourth part is devoted to carbonyl containing polyfunctional molecules. After a short reminder of the methods of determination of gas-phase basicity and the underlying physicochemical concepts, specific examples are examined under two major chapters. In the first one, aliphatic and unsaturated (conjugated and cyclic) ketones, diketones, ketoalcohols, and ketoethers are considered. A second chapter describes the protonation energetic of gaseous acids and derivatives including diacids, diesters, diamides, anhydrides, imides, ureas, carbamates, amino acid derivatives, and peptides. Experimental data were re-evaluated according to the presently adopted basicity scale. Structural and energetic information given by G3 and G4 quantum chemistry computations on typical systems are presented.

A Fast Chromatographic Method for Estimating Lipophilicity and Ionization in Nonpolar Membrane-Like Environment.

This study describes the design and implementation of a new chromatographic descriptor called log k'80 PLRP-S that provides information about the lipophilicity of drug molecules in the nonpolar environment, both in their neutral and ionized form. The log k'80 PLRP-S obtained on a polymeric column with acetonitrile/water mobile phase is shown to closely relate to log Ptoluene (toluene dielectric constant ε ∼ 2). The main intermolecular interactions governing log k'80 PLRP-S were deconvoluted using the Block Relevance (BR) analysis. The information provided by this descriptor was compared to ElogD and calclog Ptol, and the differences are highlighted. The "charge-flush" concept is introduced to describe the sensitivity of log k'80 PLRP-S to the ionization state of compounds in the pH range 2 to 12. The ability of log k'80 PLRP-S to indicate the propensity of neutral molecules and monoanions to form Intramolecular Hydrogen Bonds (IMHBs) is proven through a number of examples.

Deuterium isotope effects on 13C chemical shifts of negatively charged NH N systems.

Deuterium isotope effects on (13)C chemical shifts are investigated in anions of 1,8-bis(4-toluenesulphonamido)naphthalenes together with N,N-(naphthalene-1,8-diyl)bis(2,2,2-trifluoracetamide) all with bis(1,8-dimethylamino)napthaleneH(+) as counter ion. These compounds represent both "static" and equilibrium cases. NMR assignments of the former have been revised. The NH proton is deuteriated. The isotope effects on (13)C chemical shifts are rather unusual in these strongly hydrogen bonded systems between a NH and a negatively charged nitrogen atom. The formal four-bond effects are found to be negative indicating transmission via the hydrogen bond. In addition, unusual long range effects are seen. Structures, (1)H and (13)C NMR chemical shifts and changes in nuclear shieldings upon deuteriation are calculated using density functional theory methods.

Quantification of hydrogen bond energy based on equations using spectroscopic, structural, QTAIM-based, and NBO-based descriptors which calibrated by the molecular tailoring approach.

CONTEXT: Hydrogen bonds critically influence the structure and properties of both organic molecules and biomolecules, as well as supramolecular assemblies. For this reason, the development and elaboration of methods for quantitative assessment of hydrogen bond energy is an urgent challenge. In this study, using a large series of hydroxycarbonyl aliphatic compounds with the O‒H···O = C intramolecular hydrogen bond, a bank of hydrogen bond descriptors was created, including spectroscopic, structural, QTAIM-based, and NBO-based parameters. It was shown that the O‒H vibration frequency, OH chemical shift as the spectroscopic descriptors, the O···H hydrogen bond length, O···O distance, and O‒H covalent bond length as the structural descriptors, the electron density and its Laplacian, electron potential energy density in the hydrogen bond critical point, the electron density at the ring critical point as the QTAIM-based descriptors change in a correlated manner. The same correlation is found in change of the charge transfer energy through a hydrogen bond, the occupancy of the O‒H bond antibonding orbital, the Wiberg indices of the O···H hydrogen bond, and the O‒H covalent bond, as well as the polarization of the O‒H bond, which are the NBO-based descriptors. It was also recognized that the specified descriptors from the spectroscopic, structural, QTAIM-based, and NBO-based categories are functionally related to the values of intramolecular hydrogen bond energy, quantified via the molecular tailoring approach. This allowed one to obtain a system of equations for quantitative estimation of intramolecular hydrogen bond energy based on the spectroscopic, structural, QTAIM, and NBO descriptors, which makes such quantification more dependable and reliable. METHODS: To obtain the spectroscopic descriptors, the vibrational spectra and shielding constants were calculated using the GIAO method. Structural descriptors were obtained for the equilibrium geometry of molecules, calculated at the MP2(FC)/6-311 + + (2d,2p) level using the Gaussian 09 program. The QTAIM-based descriptors were calculated using the AIMAll program within the framework of the quantum theory "Atoms in Molecules." The NBO-based descriptors were calculated using the NBO 3.1 program implemented into Gaussian 09. To quantify the energy of intramolecular hydrogen bonds, molecular fragmentation was used within the molecular tailoring approach.