Effect Of Intermolecular Hydrogen Bonds Research Articles

The influence of hydrogen bonding between different crystallization tendency drugs and PVPVA on the stability of amorphous solid dispersions

Amorphous solid dispersion (ASD) is one of the formulation strategies for drugs displaying low solubility and low oral bioavailability. In this study, high drug-loaded ASDs of drugs with different crystallization tendencies were prepared by spray drying. The aim was to investigate the influence of hydrogen bonding between the drug and the model polymer PVPVA on the physical stability of ASDs containing drugs with different crystallization tendencies. From the 60-day stability study results, the intermolecular hydrogen bonding has a considerable stabilizing effect on the ASDs of the drug with a moderate crystallization tendency. Nimesulide (hydrogen bond donor) can maintain the amorphous form for a longer time than Fenofibrate (no-hydrogen bond donor) during storage. In the ASDs with fast crystallization tendency drugs (naproxen and caffeine), intermolecular hydrogen bonds are not very effective in preventing drug crystallization, and the effect on the stability of ASD is relatively weak. However, for drugs with a slow tendency to crystallize (indomethacin and miconazole), the ASDs remained in an amorphous state during the monitored storage period, making it impossible to compare the effect of intermolecular hydrogen bonds on the stability of this type of ASDs. It also reveals that intermolecular hydrogen bonds can increase the drug loading capacity of ASDs. The relationship between drug loading and ASD stability was further analyzed by the state diagram. This study clearly pointed out that the physical stability of ASDs of drugs with different crystallization tendencies is affected to a different extent by intermolecular hydrogen bonds.

Direct Determination of the Relationship between the Intramolecular Oxygen-Hydrogen Bond Length and Its Stretching Vibrational Frequency of the Methanol Molecule in the Liquid State.

Time-of-flight (TOF) neutron diffraction measurements on pure liquid deuterated methanol and concentrated methanolic LiClO4 and LiTFSA solutions have been carried out to investigate the effect of intermolecular hydrogen bonds on the intramolecular O-D distance (rOD) of the methanol molecule in the liquid state. Intramolecular parameters for the methanol molecule are determined by the least-squares fitting analysis of the neutron total interference term observed in the high-Q region. Attenuated total reflection (ATR) IR spectra have been measured for methanolic solutions of natural abundance to determine the gravitational center frequency (νOH) of the stretching vibrational band of the methanol molecule. The relationship between rOD and νOH is approximated well by a linear function. The value dνOH/drOD = -17000 ± 3000 cm-1 Å-1 has been derived from the slope of the fitted function. It has been revealed that the O-D bond length of the methanol molecule is sensitively affected by the intermolecular hydrogen bonding interaction.

Effect of intermolecular hydrogen bonds on the proton transfer and fluorescence characteristics of 1′-hydroxy-2′-acetonaphthone

1′-hydroxy-2′-acetonaphthone (HAN) is a useful fluorescence probe based on excited state intramolecular proton transfer (ESIPT). A number of experiments had explored the fluorescence properties of HAN in different microenvironments and applied HAN to bioimaging. However, the mechanism of fluorescence properties of HAN in different microenvironments was not been fully reported. Thus, our research aims to investigate the proton transfer (PT) and fluorescence characteristics of HAN in different microenvironments, focusing on revealing the hydrogen bond dynamics in high-polar aqueous solution (HAN-H2O) and low-polar hydrophobic pocket of bovine serum albumin by the density functional theory (DFT) and time-dependent density functional theory (TD-DFT). Explicit water molecules were placed around HAN to simulate the hydrogen bond interactions between HAN and the water molecules in an aqueous solution. The intermolecular hydrogen bonds slightly affect the geometric structures of HAN, but would inhibit the ESIPT process while increasing the charge transfer distance, leading to red shift of fluorescence. Upon photoexcitation, the intramolecular hydrogen bond had been strengthened, providing the driving force of PT, which resulted in HAN and HAN-H2O undergoing ultrafast ESIPT process. Meanwhile, after photoexcitation, the intermolecular hydrogen bonds were significantly enhanced, decreasing the energy of HAN-H2O in the excited state and promoted the radiationless deactivation of HAN-H2O. Therefore, HAN has weak fluorescence in the aqueous solution.

The role of intramolecular and intermolecular hydrogen bonding effect for adenine-containing polyimide films

A series of adenine-containing polyimides (APIs) with intramolecular hydrogen bonding (HB) were prepared from N 1 -(9-(4-aminophenyl)- 9H-purin-6-yl)-2-methoxybenzene-1,4-diamine (b-H-MeO-APA) and commercial dianhydrides. And a systematic comparison between intramolecular and intermolecular HB effects was made using APIs with (b-H-MeO-APIs) and without (b-H-H-API) methoxy group. FTIR indicated that the occurrence of intramolecular HB originated from the side MeO group ortho to -NH-. XRD indicated that the introduction of side group MeO and corresponding intramolecular HB could destroy the orderly stacking of b-H-H-APIs. Birefringence and polarized ATR FTIR studies showed that the groups and chains in b-H-MeO-APIs films could also be simultaneously self-arranged in the in-plane direction. In contrast, the orientation degree in the in-plane direction is generally lower than that of b-H-H-APIs. The b-H-MeO-APIs films showed lower water absorption, higher Tg, and lower CTE compared to b-H-H-APIs films, which indicates that the introduction of intramolecular HB may have some positive influence in controlling water absorption, Tg, and CTE.

Uncovering the relationship between the structure and acid-base properties for hyperbranched polyester-polyols self-assembled on carbon surfaces

Abstract The self-assembly of three different generations of hyperbranched polyester-polyol polymers, based on 2,2-bis(methylol)propionic acid units (H20, H30, and H40 Boltorn®), on carbon electrodes was studied. The physico-chemical properties of this family of polymers confined on a surface were explored by electrochemical impedance spectroscopy (EIS) and atomic force microscopy (AFM). Surface pKa of the hyperbranched polymer layers were determined by impedimetric titration by EIS based on the variation in the charge transfer resistance of the electroactive redox probe [Fe(CN)6]4−/[Fe(CN)6]3− at different pH. AFM was used to characterize the surface topography and also its viscoelastic properties by the acquisition of phase images. The relation between structure and acid-base properties can be explained in terms of a rearrangement of the layer due to the effect of intermolecular hydrogen bonds and adsorbate-substrate interactions. In this study, we report a powerful, versatile and yet simple procedure for functionalizing carbon materials surfaces without pre-treatment requirements, which could be useful to generate promising platforms for the development of sensors and drug delivery systems.

Theoretical insights into aggregation-induced helicity modulation of a perylene bisimide derivative.

Formation of helical chiroptical self-assemblies via noncovalent interaction is a widely observed phenomenon in nature, the mechanism of which remains insufficiently understood. Employing an amphiphilic perylene-sugar dyad molecule (PBI-HAG) as an example, we report that the modulatable supramolecular helicity may emerge from an aggregating process that is dominated by competition between two types of noncovalent interaction: hydrogen bonding and π-π stacking. The interplay between these two driving forces, which is greatly affected by the solvent environment, determines the morphology the supramolecular assembly of PBI-HAGs. In particular, a non-layered supramolecular structure was formed in octane owing to stabilization effects of intermolecular hydrogen bonds, whereas a layered supramolecular structure was formed in water because of energetically favorable π-π stacking of aromatic rings. The formation of distinct supramolecular architectures in different solvents was reinforced by simulated circular dichroism spectra, which show opposite signals consistent with experimental observations. The results of this study could help us understand aggregation-induced supramolecular chirality of noncovalent self-assemblies. Graphical abstract Left Typical structures of amphiphilic perylene-sugar dyad (PBI-HAG) aggregates in different octane and water. Right Simulated CD and UV-Vis spectra of core PBIs aggregates in octane and water.

Influence of Hydrogen Bonding on the Surface Diffusion of Molecular Glasses: Comparison of Three Triazines.

Surface grating decay measurements have been performed on three closely related molecular glasses to study the effect of intermolecular hydrogen bonds on surface diffusion. The three molecules are derivatives of bis(3,5-dimethyl-phenylamino)-1,3,5-triazine and differ only in the functional group R at the 2-position, with R being C2H5, OCH3, and NHCH3, and referred to as "Et", "OMe", and "NHMe", respectively. Of the three molecules, NHMe forms more extensive intermolecular hydrogen bonds than Et and OMe and was found to have slower surface diffusion. For Et and OMe, surface diffusion is so fast that it replaces viscous flow as the mechanism of surface grating decay as temperature is lowered. In contrast, no such transition was observed for NHMe under the same conditions, indicating significantly slower surface diffusion. This result is consistent with the previous finding that extensive intermolecular hydrogen bonds slow down surface diffusion in molecular glasses and is attributed to the persistence of hydrogen bonds even in the surface environment. This result is also consistent with the lower stability of the vapor-deposited glass of NHMe relative to those of Et and OMe and supports the view that surface mobility controls the stability of vapor-deposited glasses.

Experimental and Theoretical Study of the Raman Spectra of Ammonium Thiosulfate Solution

The Raman spectra of ammonium thiosulfate solution have been experimentally measured and several typical Raman peaks of S 2 o 3 2 − in ammonium thiosulfate solution were observed. We found that there is a linear relationship between the concentration of S 2 o 3 2 − and the corresponding intensity and area of the Raman peaks. To study the possible effect of intermolecular hydrogen bonds on the vibration of S 2 o 3 2 − , its Raman spectra were calculated using the Hartree–Fock Hamiltonian with the 6-31+G(d) basis set in the gas phase, hydrated phase (simulating intermolecular hydrogen bonds by adding two water molecules), and by the self-consistent reaction field model (SCRF). The study shows that in the gas and hydrated phases, the wavenumbers of peaks in the Raman spectra are in good agreement with the experimental values in the low-frequency region, and there is a red shift in the highfrequency region. In contrast, in both the low and high-frequency regions, the wavenumbers in the SCRF model are closer to the experimental values than those in the former two phases. This shows that the SCRF model is most suitable for the calculation of the Raman spectra of S 2 o 3 2 − in ammonium thiosulfate solution.

Study on Intermolecular Forces of Corn Gluten with the Chemical Reagent Treatment

Corn gluten were steeped with different chemical reagents, 2%urea, 5%tween80, 5% NaCl, 2%L - cysteine, using distilled water as control. Intermolecular forces in corn gluten under different reagents were analyzed using the amount of free starch measuring by iodine calorimetry. By the light microscope, intermolecular structure transformation in corn gluten was analyzed before the treatment and after. The results show that Urea, twain, NaCl, and L-cysteine all can make the starch that closely combined with protein migrate away, in which the effect of L-cysteine and NaCl were better, releasing more free starch. It is found through microscopic observation that the starch granule existing in corn gluten is small granule from cutin endosperm, and microscopic observation results consistent with the free starch results. By analysis of the amount of free starch and the microscopic structure change of corn gluten and the mechanism of measuring intermolecular forces with the chemical reagent, it is demonstrated that disulfide bond and electrostatic attraction were main intermolecular forces in corn gluten, which was the main reason for the search combining with the protein .The effect of intermolecular hydrogen bonds and hydrophobic interaction were weaker.

Intermolecular hydrogen-bonding effects on photophysics and photochemistry

Intermolecular hydrogen bonding, as an important site-specific interaction between hydrogen donor and acceptor molecules both in the gas phase and in solution, plays a significant role and has a remarkable influence on the photophysics and photochemistry of chromophores in the hydrogen-bonding surroundings. In recent years, the excited-state structures and dynamics of the intermolecular hydrogen bonding have been widely investigated by using both the experimental and theoretical methods. This review article focuses on the recent research progress of the important intermolecular hydrogen-bonding effects on the non-adiabatic photophysical processes and photochemical reactions. Firstly, the corresponding relationship between electronic spectral red-shift or blue-shift and excited-state intermolecular hydrogen bond strengthening or weakening has been clarified. A dynamic equilibrium induced by the intermolecular hydrogen bond strengthening in the electronically excited state of fluorenone chromophore was used to explain the steady-state spectral features. The stepwise mechanism of excited-state double proton transfer reaction for the 2-aminopyridine/acid systems was demonstrated. The role of intermolecular hydrogen bonding on the excited-state proton transfer in the sensing mechanism of fluorescent probes has also been discussed. Moreover, a dihydrogen-bonded complex formed by borane-trimethylamine and phenol showed interesting geometric structures and infared spectrum in electronically excited state.

Porphyrin Assemblies through the Air/Water Interface: Effect of Hydrogen Bond, Thermal Annealing, and Amplification of Supramolecular Chirality

Molecular assemblies of two achiral porphyrins with different substituents, 5-(4-methoxycarbonylphenyl)-10,15,20-triphenyl-21H,23H-porphine (TPPCOOMe) and 5-(4-carboxyphenyl)-10,15,20-triphenyl-21H,23H-porphine (TPPCOOH), have been fabricated by the Langmuir-Blodgett (LB) technique. It is disclosed that although only slight differences exist in the molecular skeleton of these two compounds, their interfacial assemblies display distinct chiroptical properties. It is found that weak circular dichroism (CD) signals are observed from the TPPCOOH assemblies, while in the case of the TPPCOOMe assemblies, only negligible CD signals could be detected. Interestingly, after the assemblies are subjected to a thermal annealing treatment, TPPCOOH assemblies show a distinct amplification of CD signals, while those of TPPCOOMe do not. An explanation in terms of the effect of substituents on the spreading properties of the compounds and the effect of intermolecular hydrogen bonds on the cooperative stacking of the building blocks is proposed to explain these new findings. The investigation suggests that in the present porphyrin systems, besides a nice spreading property, the cooperative interaction of various noncovalent interactions, including hydrogen bonding, π-π stacking, and hydrophobic interactions, is essentially required for the occurrence of symmetry breaking at the air/water interface.

Intramolecular and intermolecular hydrogen-bonding effects on the dipole moments and photophysical properties of some anthraquinone dyes

Absorption and fluorescence spectra of three anthraquinone dyes with various substituents and molecular size were studied in different solvents. The photo-physical behavior of a dissolved dye depends strongly on the solvent–solute interactions and solvent nature. The solvatochromic method was used to investigate dipole moments of these dyes in ground and excited states. The spectral variations were analyzed by means of linear solvation energy relationships concept proposed by Kamlet and Taft. The results conceive the nature and extend of, specific and non-specific, solvent–solute interactions.

Structure and proton donating ability of 2- and 2,5-bis(1-trifluoromethanesulfonylamido-2,2,2-trichloroethyl)pyrroles

2-(1-Trifluoromethanesulfonylamido-2,2,2-trichloroethyl)pyrrole and 2,5-bis(1-trifluoromethanesulfonylamido-2,2,2-trichloroethyl)pyrrole according to quantum chemical calculations (B3LYP/6-311G**) exist in the isomeric forms whose structure determines the formation of intramolecular hydrogen bonds NH⋯Cl, NH⋯O=S and CH⋯O=S of different strength. Potentiometric and spectroscopic acidity of these compounds is determined. From the data of IR spectroscopy their proton donating ability upon interaction with Lewis bases is shown depending on the presence of intramolecular hydrogen bonds, mutual effects of intermolecular hydrogen bonds formed by the sulfonamide and pyrrole NH groups with the base, and electronic effects of the substituents.

Conformational and thermal behavior of a pH-sensitive bolaform hydrogelator.

The phase behavior of the symmetric long-chain bolaamphiphile dotriacontan-1,1'-diyl-bis[2-(dimethylammonio)ethyl phosphate] (MePE-C32-MePE) was investigated in aqueous suspensions of different pH by transmission electron microscopy (TEM), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FT-IR). At pH 5 the compound exhibits excellent properties as a hydrogelator by forming a dense network of helically structured nanofibrils with a diameter of 3-4 nm. The phase behavior of MePE-C32-MePE is compared with the previously examined trimethylammonio analogue PC-C32-PC, whose self-assembly process seems to be exclusively driven by hydrophobic interactions. At pH 5, MePE-C32-MePE can form intermolecular hydrogen bonds between the headgroups, which causes a significantly higher stability of the nanofibrils up to at least 75 °C. In contrast, no pronounced gelling properties are observed at pH 10. Obviously, the negatively charged headgroups seem to prevent the suspension from gelling. Nevertheless, nanofibrils are formed, but at 75 °C a fragmentation into smaller aggregates occurs due to the lack of stabilizing effect of intermolecular hydrogen bonds and the destabilizing effect of the negatively charged headgroups.

Intramolecular and intermolecular hydrogen-bonding effects on photophysical properties of 2′-aminoacetophenone and its derivatives in solution

Effects of intra- and intermolecular hydrogen-bonds on the photophysical properties of 2'-aminoacetophenone derivatives (X-C6H4-COCH3) having a substituted amino group (X) with different hydrogen-bonding ability to the carbonyl oxygen (X: NH2(AAP), NHCH3(MAAP), N(CH3)2(DMAAP), NHCOCH3(AAAP), NHCOCF3(TFAAP)) are investigated by means of steady-state and time-resolved fluorescence spectroscopy and time-resolved thermal lensing. Based on the photophysical parameters obtained in aprotic solvents with different polarity and protic solvents with different hydrogen-bonding ability, the characteristic photophysical behavior of the 2'-aminoacetophenone derivatives is discussed in terms of hydrogen-bonding and n,pi*-pi,pi* vibronic coupling. The dominant deactivation process of AAP and MAAP in nonpolar aprotic solvents is the extremely fast internal conversion (k(ic)= 1.0 x 10(11) s(-1) for AAP and 3.9 x 10(10) s(-1) for MAAP in n-hexane). The internal conversion rates of both compounds decrease markedly with increasing solvent polarity, suggesting that vibronic interactions between close-lying S1(pi,pi*) and S2(n,pi*) states lead to the large increase in the non-radiative decay rate of the lowest excited singlet state. It is also suggested that for MAAP, which has a stronger hydrogen-bond as compared to AAP, an intramolecular hydrogen-bonding induced deactivation is involved in the dissipation of the S1 state. For DMAAP, which cannot possess an intramolecular hydrogen-bond, the primary relaxation mechanism of the S1 state in nonpolar aprotic solvents is the intersystem crossing to the triplet state, whereas in protic solvents very efficient internal conversion due to intermolecular hydrogen-bonding is induced. In contrast, the fluorescence spectra of AAAP and TFAAP, which have an amino group with a much stronger hydrogen-bonding ability, give strongly Stokes-shifted fluorescence, indicating that these compounds undergo excited-state intramolecular proton transfer reaction upon electronic excitation.

Molecular crystals: the crystal field effect on molecular electronic structure.

The effect of crystal packing on the electronic structure of organic molecules was modeled by incorporation of the external electrostatic potential into the semiempirical Hamiltonian of the molecule. An empirical correction procedure was devised in order to compensate for systematic errors in the charge distribution typical of semiempirical methods. The model was applied to 79 crystal structures belonging to various syngonies and space groups. The effect of the crystal field is subject to wide variations depending on the crystal packing motif. The difference between the effect of the crystal field on the molecular electronic structure and the solvent effect modeled with COSMO is highlighted. The effect of intermolecular hydrogen bonds on the molecular electronic structure and electronic spectra was modeled with this approach, and it does not predominate over the effect of long-range electrostatic interactions. INDO/S calculations employing the crystal electrostatic potential give an insight into the origin of crystallochromy, in particular, they properly predict color difference for several groups of polymorphs.

Flat versus twisted rotamers of 2,4-disubstituted thiazoles: the effect of intermolecular hydrogen bonds.

In the title compounds, 2-amino-4-(2-chloro-4,5-dimethoxyphenyl)-1,3-thiazole, C(11)H(11)ClN(2)O(2)S, (I), and 4-(2-chloro-4,5-dimethoxyphenyl)-2-methyl-1,3-thiazole, C(12)H(12)ClNO(2)S, (II), the dihedral angles between the thiazole moiety and the chloroaryl group are 51.61 (10) and 8.44 (14), respectively. This difference is a consequence of intermolecular hydrogen bonds forcing the stabilization of a twisted rotamer in (I). Substitution of the amino function by a methyl group precludes these contacts, giving a flat rotamer in (II).

Intermolecular hydrogen-bonding effects on the 13C NMR shielding tensor of the carbonyl carbon nucleus in a single crystal of dimedone

High-resolution 13C NMR techniques have been employed to study the effects of inter-molecular hydrogen bonding on the chemical-shielding tensor of the carbonyl carbon in a single crystal of dimedone. The principal values, in ppm, relative to an external reference of TMS were found to be σ 11 = 284.1, σ 22 = 254.9, and σ 33 = 79.0. The σ 33 axis is almost perpendicular to the plane spanned by the C sp 2 −C=O moiety, and the σ 11 axis is tilted by 22° from the C=O bond direction in that plane. The principal value of the chemical-shielding tensor which is directed along the CO bond ( σ 11 for dimedone) shows a strong downfield shift (∼50 ppm), as compared to that of acetophenone ( σ 22 = 231.5); this is undoubtedly because of the intermolecular hydrogen bonding in the former compound. The chemical-shielding tensors for the other seven chemically distinct carbon nuclei in the molecule have also been determined and a comparison is made with the chemical-shift tensors in analogous compounds.

Intermolecular hydrogen-bonding effects on13C NMR shielding for enol forms of diketones in the solid state

From high-resolution solid-state13C NMR spectra for the enol forms of some diketones, an average chemical shift of the carbonyl and enol carbons in dimedone is found to move remarkably downfield compared with the corresponding shift in DMSO-d6, which is ascribed to a strong intermolecular hydrogen bond in the solid state.

Nuclear Quadrupole and Magnetic Resonance Study of Molecular Motion in Solid HCl and DCl

Nuclear magnetic and quadrupole resonances were used to study the structure of hydrogen and deuterium chlorides below and above the transition points. The chlorine pure quadrupole resonance frequencies were measured between 20°K and the transition points, showing that a single molecular libration frequency does not fully account for the temperature dependence probably because of the effect of intermolecular hydrogen bonds. The structure of the high temperature phase was proposed as being a hindered rotational one, on the basis of the second moment of the proton magnetic resonance and of the direct observation of chlorine magnetic resonance, the latter leading to the activation energy of 0.7 kcal/mole for rotation. The self-diffusion of molecules below the melting point causes further narrowing of proton resonance line above 130°K, with an activation energy of 5.6 kcal/mole.