Solute-solvent contact by intermolecular cross relaxation. I. The nature of the water-hydrophobic interface

Intermolecular cross-relaxation rates between solute and solvent were measured by {1H} 19F nuclear magnetic resonance experiments in aqueous molecular solutions of ammonium perfluoro-octanoate and sodium trifluoroacetate. The experiments performed at three different magnetic fields provide frequency-dependent cross-relaxation rates which demonstrate clearly the lack of extreme narrowing for nuclear spin relaxation by diffusionally modulated intermolecular interactions. Supplemented by suitable intramolecular cross-relaxation, longitudinal relaxation, and self-diffusion data, the obtained cross-relaxation rates are evaluated within the framework of recent relaxation models and provide information about the hydrophobic hydration. In particular, water dynamics around the trifluoromethyl group in ammonium perfluoro-octanoate are more retarded than that in the smaller trifluoroacetate.     

19F high magnetic field NMR study of beta-ZrF4 and CeF4: from spectra reconstruction to correlation between fluorine sites and 19F isotropic chemical shifts

High magnetic field and high spinning frequency one- and two-dimensional one-pulse MAS 19F NMR spectra of beta-ZrF4 and CeF4 were recorded and reconstructed allowing the accurate determination of the 19F chemical shift tensor parameters for the seven different crystallographic fluorine sites of each compound. The attributions of the NMR resonances are performed using the superposition model for 19F isotropic chemical shift calculation initially proposed by Bureau et al. (Bureau, B.; Silly, G.; Emery, J.; Buzaré, J.-Y. Chem. Phys. 1999, 249, 85-104). A satisfactory reliability is reached with a root-mean-square (rms) deviation between calculated and measured isotropic chemical shift values equal to 1.5 and 3.5 ppm for beta-ZrF4 and CeF4, respectively.     

(Pentafluorophenyl)sulfur fluorides, 19F NMR

The low-temperature ¹⁹F NMR spectra of (pentafluorophenyl)sulfur trifluoride are explained by the trigonal bipyramid structure ( 1a ) with the pentafluorophenyl ring in the basal plane and a relatively high barrier to rotation about the C? S bond. In the presence of a hydrogen fluoride scavenger, there is a high barrier to intramolecular rearrangement of the sulfur fluorines about the sulfur atom. The single basal fluorine couples strongly with one ortho fluorine and weakly with the other, but the two apical fluorines couple equally with both ortho fluorines. A six-bond coupling between S? F and p? F is found in (pentafluorophenyl)sulfur trifluoride and in (pentafluorophenyl)-sulfinyl fluoride, but not in (pentafluorophenyl)sulfonyl fluoride.     

Interactions of trifluoroethanol with [val5]angiotensin II

Intermolecular 1H{19F} NOE experiments have been used to explore the interactions of trifluoroethanol (TFE) with the octapeptide hormone [val5]angiotensin II at temperatures from 5 to 25 degrees C. Circular dichroism spectra indicate that 40% trifluoroethanol has an influence on the conformations of the peptide, probably leading to beta-structures. Diffusion experiments show that the mean hydrodynamic radius of the peptide in 40% trifluoroethanol-water is about 8 A, consistent with significant folding of the peptide in this medium. Distance constraints derived from intramolecular NOESY data along with observed vicinal coupling constants (3JCalphaHNH) were used to develop conformations consistent with available data. Assuming that intermolecular 1H{19F} NOEs are the result of diffusive encounters of TFE and peptide molecules, it is shown that no single conformation is consistent with the experimental values of the sigmaHF cross-relaxation parameters. It is argued that the disagreements between observed and expected values of sigmaHF are the result of formation of long-lived (approximately 0.5 ns) fluoroalcohol-peptide complexes, a conclusion consonant with similar studies of other peptide-fluoroalcohol systems. Complex formation appears to be especially prevalent near the charged amino acid side chains of the hormone.     

F and C spectra of fluorinated and partially fluorinated vinyl alkyl ethers

Fluorine, hydrogen, and ¹³C NMR spectral data have been obtained for vinyl alkyl ethers containing fluorines. Some of the molecules are perfluorinated and others include hydrogen, bromine, and chlorine substituents. New generalizations regarding FF spin-spin coupling are developed and used, along with previously recognized correlations, in the confirmation of structures and the assignments of resonances. ¹³C spectroscopy, especially the analysis of ¹³C¹⁹F coupling, is critical in several of the structure determinations. Chlorine isotope effects on fluorine chemical shifts are observed when the chlorine and fluorine are attached to the same carbon, and are also used in the structure analyses. Long-range couplings between fluorines in the vinyl group and fluorines in the alkyl group are interpreted in terms of molecular geometry which allows certain of the alkyl fluorines to “touch” the fluorines cis and gem to the ether oxygen but not the fluorine trans to the oxygen. Two bond ¹³C¹⁹F coupling across the vinyl double bond is found to vary dramatically with the electronegativity of the vinyl substituents in the ethers, in accordance with previous observations for olefins.     

Effects of fluorine substitution on the edge-to-face interaction of the benzene dimer

To gain some insight into the effects of fluorination on the aromatic-aromatic interactions found in protein-ligand complexes, like those observed in the set of N-(4-sulfamylbenzoyl)benzylamine (SBB) inhibitors bound to Human Carbonic Anhydrase II (HCAII), we have produced potential energy curves for the edge-to-face interactions of a set of fluorinated benzene dimer compounds. All calculations were carried out at the MP2/aug-cc-pVDZ level of theory using the counterpoise method of Boys and Bernardi (Boys, S. F.; Bernardi, F. Mol. Phys. 1970, 19, 553) to account for the basis set superposition error. Fluorine substitutions are made onto the face molecule of the edge-to-face benzene dimer. As one might expect, the substitution of additional fluorines into this system generally resulted in a decrease of the binding energy. It was also found that the positioning of the fluorine substituents on isosubstituted compounds has a large effect on the total binding energy of these types of systems. More specifically, complexes with fluorines that are substituted closer to the hydrogen atoms of the edge benzene will tend to be stabilized by an electrostatic interaction between the partially negative fluorine atoms and the partially positive hydrogen atoms. However, our findings do not explain the recent crystallographic findings for the SBB-HCAII protein-ligand complex, where increased fluorination resulted in closer edge-to-face contacts, which suggests that there are factors, other than edge-to-face aromatic interactions, influencing this system's behavior.     

Intermolecular nuclear spin—spin coupling and scalar relaxation. A quantum-mechanical and statistical-mechanical study for the aqueous fluoride ion

Coupling between¹⁹F and magnetic nuclei (¹H,¹⁷O) in water molecules in the first hydration sphere of F^? are calculated using Monte Carlo simulations. The simulations are based on intermolecular potentials from the literature and on variations of coupling constants with geometry obtained by coupled Hartree-Fock calculations. Average coupling constants are ≈20–40 Hz. Intermolecular scalar relaxation in aqueous solutions is discussed.     

Spin relaxation effects in photochemically induced dynamic nuclear polarization spectroscopy of nuclei with strongly anisotropic hyperfine couplings

We describe experimental results and theoretical models for nuclear and electron spin relaxation processes occurring during the evolution of 19F-labeled geminate radical pairs on a nanosecond time scale. In magnetic fields of over 10 T, electron-nucleus dipolar cross-relaxation and longitudinal DeltaHFC-Deltag (hyperfine coupling anisotropy--g-tensor anisotropy) cross-correlation are shown to be negligibly slow. The dominant relaxation process is transverse DeltaHFC-Deltag cross-correlation, which is shown to lead to an inversion in the geminate 19F chemically induced dynamic nuclear polarization (CIDNP) phase for sufficiently large rotational correlation times. This inversion has recently been observed experimentally and used as a probe of local mobility in partially denatured proteins (Khan, F.; et al. J. Am. Chem. Soc. 2006, 128, 10729-10737). The essential feature of the spin dynamics model employed here is the use of the complete spin state space and the complete relaxation superoperator. On the basis of the results reported, we recommend this approach for reliable treatment of magnetokinetic systems in which relaxation effects are important.     

CF3 Rotation in 3-(Trifluoromethyl)phenanthrene: Solid State 19F and 1H NMR relaxation and Bloch-Wangsness-Redfield theory

We have observed and modeled the 1H and 19F solid-state nuclear spin relaxation process in polycrystalline 3-(trifluoromethyl)phenanthrene. The relaxation rates for the two spin species were observed from 85 to 300 K at the low NMR frequencies of omega/2pi = 22.5 and 53.0 MHz where CF3 rotation, characterized by a mean time tau between hops, is the only motion on the NMR time scale. All motional time scales (omegatau < 1, omegatau approximately 1, and omegatau > 1) are observed. The 1H spins are immobile on the NMR time scale but are coupled to the 19F spins via the unlike-spin dipole-dipole interaction. The temperature dependence of the observed relaxation rates (the relaxation is biexponential) shows considerable structure and a thorough analysis of Bloch-Wangsness-Redfield theory for this coupled spin system is provided. The activation energy for CF3 rotation is 11.5 +/- 0.7 kJ/mol, in excellent agreement with the calculation in a 13-molecule cluster provided in the companion paper where the crystal structure is reported and detailed ab initio electronic structure calculations are performed [Wang, X.; Mallory F. B.; Mallory, C. W; Beckmann, P. A.; Rheingold, A. L.; Francl, M. M J. Phys. Chem. A 2006, 110, 3954].     

Conformation analysis and molecular mobility of ethylene and tetrafluoroethylene copolymer using solid-state 19F MAS and 1H --> 19F CP/MAS NMR spectroscopy

The changes in the conformation and molecular mobility accompanied by a phase transition in the crystalline domain were analyzed for ethylene (E) and tetrafluoroethylene (TFE) copolymer, ETFE, using variable-temperature (VT) solid-state 19F magic angle spinning (MAS) and 1H --> 19F cross-polarization (CP)/MAS NMR spectroscopy. The shifts of the signals for fluorines in TFE units to higher frequency and the continuing decrease and increase in the T1rho(F) values suggest that conformational exchange motions exist in the crystalline domain between 42 and 145 degrees C. Quantum chemical calculations of magnetic shielding constants showed that the high-frequency shift of TFE units should be induced by trans to gauche conformational changes at the CH2-CF2 linkage in the E-TFE unit. Although the 19F signals of the crystalline domain are substantially overlapped with those of the amorphous domain at ambient probe temperature (68 degrees C), they were successfully distinguished by using the dipolar filter and spin-lock pulse sequences at 145 degrees C. The dipolar coupling constants for the crystalline domain, which can be estimated by fitting the dipolar oscillation behaviors in the 1H --> 19F CP curve, showed a significant decrease with increasing temperature from 42 to 145 degrees C. This is due to the averaging of 1H-19F dipolar interactions originating from the molecular motion in the crystalline domain. The increase in molecular mobility in the crystalline domain was clearly shown by VT T1rho(F) and 1H --> 19F CP measurements in the phase transition temperature range.     

Structure and dynamics of perfluoroalkane/beta-cyclodextrin inclusion compounds as studied by solid-state 19F MAS and 1H -->19F CP/MAS NMR spectroscopy

The molecular structure and dynamics of novel inclusion compounds (ICs) consisting of n-perfluoroalkane (PFA) guests and beta-cyclodextrin (beta-CD) host (PFA/beta-CD) have been investigated using 19F magic angle spinning (MAS) and 1H-->19F cross polarization (CP)/MAS NMR spectroscopy with the aid of thermal analyses, FT-IR spectroscopy, and X-ray diffraction method. The ICs of C9F20/beta-CD and C20F42/beta-CD were successfully obtained as precipitates from mixtures of respective PFAs and saturated aqueous solution of beta-CD. The wide-angle X-ray diffraction (WAXD) revealed that C9F20/beta-CD forms a channel-type crystallite, while C20F42/beta-CD is nearly amorphous at room temperature. The structural orders in both ICs increase at elevated temperatures. The 19F NMR signals obtained by the direct polarization (DP) method for PFA/beta-CD are resonated at higher frequencies than those for original PFA. This can be ascribed to the lower dielectric environment of the beta-CD cavity. Above 80 degrees C, 1H-->19F CP/MAS NMR technique revealed that C9F20 molecules undergo vigorous molecular motion and partly come out of the beta-CD channel. However, the guests hardly degrade or evaporate unless the host is pyrolytically decomposed above ca. 300 degrees C. The spin-lattice relaxation times in the laboratory frame for 19F (T1F) are almost identical for all the fluorines in PFA/beta-CD at each temperature, while significantly different values were observed for fluorines in neat PFA. This indicates that effective intramolecular spin diffusion occurs within a PFA molecule included in beta-CD.     

Hydrogen-bond symmetry in difluoromaleate monoanion

The symmetry of the hydrogen bond in hydrogen difluoromaleate monoanion is probed by X-ray crystallography and by the NMR method of isotopic perturbation in water, in two aprotic organic solvents, and in an isotropic liquid crystal. The X-ray crystal structure of potassium hydrogen difluoromaleate shows a remarkably short O-O distance of 2.41 ? and equal O-H distances of 1.206 ?, consistent with a strong and symmetric hydrogen bond. Incorporation of (18)O into one carboxyl group allows investigation of the symmetry of the H-bond in solution by the method of isotopic perturbation. The (19)F NMR spectra of the mono-(18)O-substituted monoanion in water, CD(2)Cl(2), and CD(3)CN show an AB spin system, corresponding to fluorines in different environments. The difference is attributed to the perturbation of the acidity of a carboxylic acid by (18)O, not to the mere presence of the (18)O, because the mono-(18)O dianion shows equivalent fluorines. Therefore, it is concluded that the monoanion exists as an equilibrating pair of interconverting tautomers and not as a single symmetric structure not only in water but also in organic solvents. However, in the isotropic liquid crystal phase of 4-cyanophenyl 4-heptylbenzoate, tetrabutylammonium hydrogen difluoromaleate-(18)O shows equivalent fluorines, consistent with a single symmetric structure. These results support earlier studies, which suggested that the symmetry of hydrogen bonds can be determined by the local environment.     

New application of proton nuclear spin relaxation unraveling the intermolecular structural features of low-molecular-weight organogel fibers

Proton nuclear spin relaxation has been for the first time extensively used for a structural and dynamical study of low-molecular-weight organogels. The gelator in the present study is a modified phenylalanine amino acid bearing a naphthalimide moiety. From T(1) (spin-lattice relaxation time in the laboratory frame) and T(1ρ) (spin-lattice relaxation time in the rotating frame) measurements, it is shown that the visible gelator NMR spectrum below the liquid-gel transition temperature corresponds to a so-called isotropic compartment, where gelator molecules behave as in a liquid phase but exchange rapidly with the molecules constituting the gel structure. This feature allows one to derive, from accessible parameters, information about the gel itself. Nuclear Overhauser effect spectroscopy (NOESY) experiments have been exploited in view of determining not only cross-relaxation rates but also specific longitudinal rates. The whole set of relaxation parameters (at 25 °C) leads to a correlation time of 5 ns for gelator molecules within the gel structure and 150 ps for gelator molecules in the isotropic phase. This confirms, on one hand, the flexibility of the organogel fibers and, on the other hand, the likely presence of clusters in the isotropic phase. Concerning cross-relaxation rates, a thorough theoretical investigation in multispin systems of direct and relayed correlations in a NOESY spectrum allows one to make conclusions about contacts (around 2-3 ?) not only between naphtalimide moieties of different gelator molecules but also between the phenyl ring and the naphtalimide moiety again of different gelator molecules. As a result, not only is the head-to-tail structure of amino acid columns confirmed but also the entangling of nearby columns by the naphthalimide moieties is demonstrated.     

Weak Intermolecular Hydrogen Bonds with Fluorine: Detection and Implications for Enzymatic/Chemical Reactions,Chemical Properties,and Ligand/Protein Fluorine NMR Screening

It is known that strong hydrogen‐bonding interactions play an important role in many chemical and biological systems. However, weak or very weak hydrogen bonds, which are often difficult to detect and characterize, may also be relevant in many recognition and reaction processes. Fluorine serving as a hydrogen‐bond acceptor has been the subject of many controversial discussions and there are different opinions about it. It now appears that there is compelling experimental evidence for the involvement of fluorine in weak intramolecular or intermolecular hydrogen bonds. Using established NMR methods, we have previously characterized and measured the strengths of intermolecular hydrogen‐bond complexes involving the fluorine moieties CH₂F, CHF₂, and CF₃, and have compared them with the well‐known hydrogen‐bond complex formed between acetophenone and the strong hydrogen‐bond donor p‐fluorophenol. We now report evidence for the formation of hydrogen bonds involving fluorine with significantly weaker donors, namely 5‐fluoroindole and water. A simple NMR method is proposed for the simultaneous measurement of the strengths of hydrogen bonds between an acceptor and a donor or water. Important implications of these results for enzymatic/chemical reactions involving fluorine, for chemical and physical properties, and for ligand/protein ¹⁹F NMR screening are analyzed through experiments and theoretical simulations.     

Nuclear magnetic resonance spectra of polyfluorobuta-1,3-dienes. Part II [1]. Variable temperature study of two 2-azabutadienes

The two perfluoro-azadienes CF₂N.CRCF₂ (R = CF₃ or CF₂Cl) show temperature dependent ¹⁹F n.m.r. spectra, with non-equivalent fluorine nuclei of the CF₂N portion at low temperatures, which coalesce due to inversion at the nitrogen at higher temperatures (ΔG3 = 60 kJ mol^?1). N.m.r. parameters have been obtained. One of the five-bond FF coupling constants is much larger ($\text{ca}$. 24 Hz) than the remainder (0·5–5·5 Hz), possibly due to ‘through-space’ coupling of fluorines in the $\text{cis}$-skew conformation.     

Application of the 19F NMR technique to observe binding of the general anesthetic halothane to human serum albumin.

19F NMR techniques were employed to characterize the binding property of the widely used general anesthetic halothane with human serum albumin (HSA). It was found that 19F(1H) NOE and 2D 1H-19F HOESY experiments detected intermolecular NOEs between halothane 19F and HSA protons. Measurements of the diffusion coefficients for halothane were also carried out by 1H and 19F NMR, indicating the interaction of halothane with HSA. The present results indicate that these techniques are very suitable to identify a fluorine-containing ligand binding with a protein receptor in the drug-discovery process.     

Fluorine NMR. Spectra of conformationally constrained Gem-difluorocyclohexanes

The ¹⁹F chemical shifts and geminal coupling constants have been measured for 3,3-dimethyl- (I), 3,3,5-trimethyl- (II) and 3,3,5,5-tetramethyl-1, 1-difluorocyclohexane (III) and 3,3-difluorobicyclo [3.2.1]octane (IV). The Eyring parameters for the ring inversion were obtained for I and III. Representative values for the Arrhenius activation energy (Ea), ΔG?, ΔH?, and ΔS? are: 11.0, 9.4, 10.4 kcal/mole and 4.5 e.u. for I, and 10.0, 8.3, 9.7 kcal/mole and 8.3 e.u. for III. It appears that the syn-axial methyl-fluorine interaction has a negligible effect on the inversion process. However, the syn-axial methyl-methyl interaction, as found in III, significantly increases the rate of inversion. Substituent effects on the ¹⁹F shifts are marked. Introduction of methyl at C-3 in an equatorial position leads to shielding of the equatorial and axial fluorines (+1.8 and + 1.3 ppm). Substitution in the axial C-3 position causes deshielding of the equatorial and axial fluorines (?5.9 and ?4.9 ppm).     

Control of wettability of molecularly thin liquid films by nanostructures

The patterning of liquid thin films on solid surfaces is very important in various fields of science and engineering related to surfaces and interfaces. A method of nanometer-scale patterning of a molecularly thin liquid film on a silicon substrate using the lyophobicity of the oxide nanostructures has recently been reported (Fukuzawa, K.; Deguchi, T.; Kawamura, J.; Mitsuya, Y.; Muramatsu, T.; Zhang, H. Appl. Phys. Lett. 2005, 87, 203108). However, the origin of the lyophobicity of the nanostructure with a height of around 1 nm, which was fabricated by probe oxidation, has not yet been clarified. In the present study, the change in thickness of the liquid film on mesa-shaped nanostructures and the wettability for the various combinations of the thickness of the liquid films and the height of ridge-shaped nanostructures were investigated. These revealed that lyophobicity is caused by a lowering of the intermolecular interaction between the liquid and silicon surfaces by the nanostructure and enables the patterning of a liquid film along it. The tendency of the wettability for a given liquid film and nanostructure size can be predicted by estimating the contributions of the intermolecular interaction and capillary pressure. In this method, the height of the nanostructure can control the wettability. These results can provide a novel method of nanoscale patterning of liquid thin films, which will be very useful in creating new functional surfaces.     

Low-field approach to double resonance in nuclear quadrupole resonance of spin-1 nuclei

Using double-resonance conditions, in which the Larmor frequency of a spin-1/2 nucleus is matched to one of the nuclear quadrupole resonance frequencies of a spin-1 nucleus, the authors demonstrate increased cross relaxation between the two nuclear spin species. They calculate the cross-relaxation rate using the motionally averaged heterogeneous dipole Hamiltonian as a perturbation to the combined quadrupole and Zeeman Hamiltonians. Using this cross-relaxation rate, in addition to hydrogen and nitrogen autorelaxation rates, expressions governing spin-1/2 and spin-1 spin-lattice relaxation are determined. With ammonium nitrate, containing nitrogen (spin-1) and hydrogen (spin-1/2), increased nitrogen signal and spin-lattice relaxation are demonstrated, using fields less than 120 G. The cross-relaxation rate is also measured and an overall signal/noise improvement by a factor of 2.3+/-0.1 is attained.