Hydrogen-bonded Carboxylic Acid Dimers Research Articles

Advanced 1 H Solid-State NMR Spectroscopy on Hydrogels, 1

Summary: The nature of the pH dependent collapse of poly(methacrylic acid) (PMAA) hydrogels is investigated using recent 1H solid-state NMR methods. In aqueous solution, PMAA changes from an expanded conformation at high pHs to a compact contracted form at low pHs, where hydrogen bonds play a central role. In solid-state 1H NMR spectra, recorded under fast magic angle spinning (MAS), dried PMAA samples previously collapsed at low pHs show characteristic signals in the spectral region of the carboxylic acid protons. With the aid of 2D 1H-1H double-quantum (DQ) MAS NMR spectra, three signals can be distinguished at 8, 10.5 and 12.5 ppm, which are attributed to free carboxylic groups and two different types of hydrogen bonded forms, respectively. The 12.5 ppm signal arises from the hydrogen bond with the shortest HH distance, corresponding to the form that is most stable with respect to increasing temperature and pH. The weaker hydrogen-bonded form (with a signal at 10.5 ppm) requires a slightly lower pH, while the free acid signal (at 8 ppm) emerges under the most acidic medium. Moreover, the stabilities of the hydrogen-bonded carboxylic acid dimers can be inferred from the proton-proton distances within the dimers, i.e. (275 ± 5) pm and (295 ± 15) pm for the protons at 12.5 and 10.5 ppm, respectively, which are determined by means of DQ MAS sideband patterns. Both the stability of the hydrogen bonds and the acidity of the protons may be related to the stereochemistry and the conformation of the PMAA chains.

Supramolecular assemblies of hydrogen-bonded carboxylic acid dimers mediated by phenyl-pentafluorophenyl stacking interactions.

Supramolecular assemblies of hydrogen-bonded carboxylic acid dimers mediated by phenyl-pentafluorophenyl stacking interactions.

Reactivity differences of indomethacin solid forms with ammonia gas.

The present study deals with the acid-base reaction of three solid-state forms of the nonsteroidal antiinflammatory drug indomethacin with ammonia gas. X-ray powder diffraction, optical microscopy, gravimetry, and spectroscopic methods were employed to establish the extent of the reaction as well as the lattice changes of the crystal forms. The glassy amorphous form readily reacts with ammonia gas to yield a corresponding amorphous ammonium salt. In addition, the metastable crystal form of indomethacin (the alpha-form) also reacts with ammonia gas, but produces the corresponding microcrystalline ammonium salt. This reaction is anisotropic and propagates along the a-axis of the crystals. The stable crystal form (the gamma-form), however, is inert to ammonia gas. Amorphous indomethacin can react with ammonia gas because it has more molecular mobility and free volume. The reactivity differences between the alpha- and gamma-forms are dictated by the arrangement of the molecules within the respective crystal lattices. The recently determined crystal structure of the metastable alpha-form of indomethacin (monoclinic P2(1) with Z = 6, V = 2501.8 A(3), D(c) = 1.42 g.cm(-3)) has three molecules of indomethacin in the asymmetric unit. Two molecules form a mutually hydrogen-bonded carboxylic acid dimer, while the carboxylic acid of the third molecule is hydrogen bonded to one of the amide carbonyls of the dimer. The carboxylic acid groups of the alpha-form are exposed on the [100] faces and are accessible to attack by ammonia gas. After one layer of molecules reacts, the reactive groups in the subsequent layer are accessible to the ammonia gas. This process proceeds along the a-axis until the ammonia gas has penetrated the entire crystal. In contrast to the alpha-form, the gamma-form has a centrosymmetric crystal structure in which the hydrogen-bonded carboxylic acid dimers are not accessible to ammonia gas because they are caged inside a hydrophobic shield comprising the remainder of the indomethacin molecule. In view of the significantly lower density of the stable gamma-form as compared to the metastable alpha-form (1.37 and 1.42 g cm(-3), respectively), it became apparent that the reactivity of the crystal forms depends exclusively on the molecular arrangement and not on the packing density of the indomethacin crystals.

Infrared Characterization and Determination of Self-Association Equilibrium Constants for Methacrylic Acid Copolymers

The synthesis of essentially random methacrylic acid (MAA) copolymers is reported. Precursor copolymers of styrene (ST) or 2,3-dimethylbutadiene (DMB) and a tert-butyldimethylsilylmethacrylate comonomer were synthesized initially by free-radical solution polymerization, followed by silyl deprotection to yield the desired amorphous MAA copolymers. The infrared characterization of these copolymers is discussed with particular emphasis placed on the effect of temperature and composition on hydrogen bonding, the formation of anhydrides at elevated temperatures, and quantitative measurements, leading to an estimation of the dimensionless equilibrium constant describing the self-association of MAA moieties. Comparisons are made to low molecular weight analogues and previous studies on ethylene-co-methacrylic acid copolymers. An important experimental finding is that the number of hydrogen-bonded carboxylic acid dimers that are formed at equilibrium is a strong function of chain stiffness.

Infrared study of alkyl carboxylic acids in CCl 4 and/or CHCl 3 solutions

Infrared data for acetic acid, propionic acid, butyric acid, isobutyric acid and trimethylacetic acid in 0.2 g 100 ml −1 CHCl 3 and/or CCl 4 solutions are included in this study. The ν(C=O) and ν op(C=O) 2 modes are apparently affected by both inductive and steric effects. Intermolecularly hydrogen-bonded complexes are suggested to be formed between the carbonyl oxygen atom of the carboxylic acids and the chloroform proton and the CO 2H proton of the carboxylic acids and the Cl atom of chloroform, and these complexes change as the mole% CHCl 3/CCl 4 increases. The concentration of the solution complexes formed with the intermolecularly hydrogen-bonded carboxylic acid dimer decreases, while the concentration of the solution complexes formed between the RCO 2H monomer increases as the mole% CHCl 3/CCl 4 increases.

Crystal structure and hydrogen-bonding system of cholic acid hemihydrate, C24H40O5�1/2H2O

Crystals of the hemihydrate of this bile acid are hexagonal, space groupP6522, a=b=13.736(8)A,c=85.06(6)A,V=13,899A3. The asymmetric unit contains two independent steroid molecules and one water molecule, the latter disordered over two nonequivalent positions.Z=12[2(C24H40O5)·1(H2O)],F(000)=5496. Structure solution by direct methods; refinement by least-squares, toR=0.072. The complex hydrogen-bond system comprises: (a) three standard ordered O-H⋯O hydrogen-bonds; (b) what is probably a symmetrically hydrogen-bonded carboxylic acid dimer, with a twofold rotation axisin the plane of the two carboxyl groups; (c) helical hydrogen-bonding chains about each 65 axis, disordered over four possible arrangements. In these helical chains, the six independent hydrogen-bonds can as a group be in either of two systems of nearly equivalent “flip-flop” arrangements: O-H⋯O ↔ O⋯H-O. Each helical system includes water, which can occupy either of two sites; thus, there is further disorder involving two sets of nonequivalent hydrogen-bonds with water as donor and acceptor. Many aggregation features here differ markedly from those in the crystal structures of either anhydrous cholic acid or cholic acid monohydrate.

Intermolecular interaction effects in the amide I vibrations of polypeptides.

Previous perturbation treatments of the Amide I vibrations of beta polypeptides are inconsistent with a detailed normal coordinate analysis of crystalline polyglycine I. This analysis indicates that the D(10) interaction constant is essentially zero, rather than the large value (about 20 cm(-1)) required by the earlier application of the perturbation theory. It is suggested that the previously neglected D(11) term should be included in the perturbation expression, and it is shown that the physical origin of such a term can be accounted for by transition dipole coupling. This mechanism is shown to give a reasonable explanation of splittings of the C=O stretching vibrations in hydrogenbonded carboxylic acid dimers. Its application to beta polypeptides provides a satisfactory interpretation of splittings in the Amide I modes.

Infrared Spectra of H-Bonded Systems : Anharmonicity of the H-Bond Vibrations in Cyclic Dimers

We present a theoretical simulation of the infrared spectra of the stretching vibrations of the H atom in hydrogen-bonded carboxylic acid dimers. We have refined a model previously proposed where the H-atom stretching vibration in an H-bond X–H···Y is coupled to the “hydrogen-bond vibration” X→–H→···Y← (we suppose that the H-atom vibration is harmonic with a frequency of oscillation depending on the X···Y distance), by the introduction of an anharmonic term (Morse potential) in the X→–H→···Y← motion. This model gives a value for the frequency of oscillation of the X→–H→···Y← motion in agreement with the observed value (in contrast to the previous model where the X→–H→···Y← motion was assumed to be harmonic), simulates in terms of delta functions the experimental spectrum rather well, and predicts the isotope effect completely. We conclude that the coupling of the H-atom stretching vibration with the hydrogen-bond vibration X→–H→···Y← together with the strong anharmonicity of the latter motion are characteristic features of stretching vibrations in hydrogen bonds, at least for weak and intermediate hydrogen bonds.