Benjamin Koeppe

Reaction pathways of proton transfer in hydrogen-bonded phenol-carboxylate complexes explored by combined UV-vis and NMR spectroscopy.

Combined low-temperature NMR/UV-vis spectroscopy (UVNMR), where optical and NMR spectra are measured in the NMR spectrometer under the same conditions, has been set up and applied to the study of H-bonded anions A··H··X(-) (AH = 1-(13)C-2-chloro-4-nitrophenol, X(-) = 15 carboxylic acid anions, 5 phenolates, Cl(-), Br(-), I(-), and BF(4)(-)). In this series, H is shifted from A to X, modeling the proton-transfer pathway. The (1)H and (13)C chemical shifts and the H/D isotope effects on the latter provide information about averaged H-bond geometries. At the same time, red shifts of the π-π* UV-vis absorption bands are observed which correlate with the averaged H-bond geometries. However, on the UV-vis time scale, different tautomeric states and solvent configurations are in slow exchange. The combined data sets indicate that the proton transfer starts with a H-bond compression and a displacement of the proton toward the H-bond center, involving single-well configurations A-H···X(-). In the strong H-bond regime, coexisting tautomers A··H···X(-) and A(-)···H··X are observed by UV. Their geometries and statistical weights change continuously when the basicity of X(-) is increased. Finally, again a series of single-well structures of the type A(-)···H-X is observed. Interestingly, the UV-vis absorption bands are broadened inhomogeneously because of a distribution of H-bond geometries arising from different solvent configurations.

Encapsulated Carboxylic Acid Dimers with Compressed Hydrogen Bonds

Interacting guests cannot exchangepartners rapidly inside capsules (as they do in bulk solution)and they are separated from solvent molecules by mechanicalbarriers. Instead, the capsule is the solvent, fixed in placearound the solute. Here we report a study on hydrogen-bonded carboxylic acid dimers as guests within an expandedcapsule assembly. It reveals evidence of compression of theguests in the isolated environment of the host.When cavitand 1 and glycoluril 2 (Figure 1) are dissolvedin deuterated mesitylene and suitable guests are present, theracemic capsule 1·2

Geometries and tautomerism of OHN hydrogen bonds in aprotic solution probed by H/D isotope effects on (13)C NMR chemical shifts.

The (1)H and (13)C NMR spectra of 17 OHN hydrogen-bonded complexes formed by CH(3)(13)COOH(D) with 14 substituted pyridines, 2 amines, and N-methylimidazole have been measured in the temperature region between 110 and 150 K using CDF(3)/CDF(2)Cl mixture as solvent. The slow proton and hydrogen bond exchange regime was reached, and the H/D isotope effects on the (13)C chemical shifts of the carboxyl group were measured. In combination with the analysis of the corresponding (1)H chemical shifts, it was possible to distinguish between OHN hydrogen bonds exhibiting a single proton position and those exhibiting a fast proton tautomerism between molecular and zwitterionic forms. Using H-bond correlations, we relate the H/D isotope effects on the (13)C chemical shifts of the carboxyl group with the OHN hydrogen bond geometries.

Solvent and H/D Isotope Effects on the Proton Transfer Pathways in Heteroconjugated Hydrogen-Bonded Phenol-Carboxylic Acid Anions Observed by Combined UV–vis and NMR Spectroscopy

Heteroconjugated hydrogen-bonded anions A···H···X(-) of phenols (AH) and carboxylic/inorganic acids (HX) dissolved in CD2Cl2 and CDF3/CDF2Cl have been studied by combined low-temperature UV-vis and (1)H/(13)C NMR spectroscopy (UVNMR). The systems constitute small molecular models of hydrogen-bonded cofactors in proteins such as the photoactive yellow protein (PYP). Thus, the phenols studied include the PYP cofactor 4-hydroxycinnamic acid methyl thioester, and the more acidic 4-nitrophenol and 2-chloro-4-nitrophenol which mimic electronically excited cofactor states. It is shown that the (13)C chemical shifts of the phenolic residues of A···H···X(-), referenced to the corresponding values of A···H···A(-), constitute excellent probes for the average proton positions. These shifts correlate with those of the H-bonded protons, as well as with the H/D isotope effects on the (13)C chemical shifts. A combined analysis of UV-vis and NMR data was employed to elucidate the proton transfer pathways in a qualitative way. Dual absorption bands of the phenolic moiety indicate a double-well situation for the shortest OHO hydrogen bonds studied. Surprisingly, when the solvent polarity is low the carboxylates are protonated whereas the proton shifts toward the phenolic oxygens when the polarity is increased. This finding indicates that because of stronger ion-dipole interactions small anions are stabilized at high solvent polarity and large anions exhibiting delocalized charges at low solvent polarities. It also explains the large acidity difference of phenols and carboxylic acids in water, and the observation that this difference is strongly reduced in the interior of proteins when both partners form mutual hydrogen bonds.

N-H stretching excitations in adenosine-thymidine base pairs in solution: pair geometries, infrared line shapes, and ultrafast vibrational dynamics.

We explore the N-H stretching vibrations of adenosine-thymidine base pairs in chloroform solution with linear and nonlinear infrared spectroscopy. Based on estimates from NMR measurements and ab initio calculations, we conclude that adenosine and thymidine form hydrogen bonded base pairs in Watson-Crick, reverse Watson-Crick, Hoogsteen, and reverse Hoogsteen configurations with similar probability. Steady-state concentration and temperature dependent linear FT-IR studies, including H/D exchange experiments, reveal that these hydrogen-bonded base pairs have complex N-H/N-D stretching spectra with a multitude of spectral components. Nonlinear 2D-IR spectroscopic results, together with IR-pump-IR-probe measurements, as also corroborated by ab initio calculations, reveal that the number of N-H stretching transitions is larger than the total number of N-H stretching modes. This is explained by couplings to other modes, such as an underdamped low-frequency hydrogen-bond mode, and a Fermi resonance with NH(2) bending overtone levels of the adenosine amino-group. Our results demonstrate that modeling based on local N-H stretching vibrations only is not sufficient and call for further refinement of the description of the N-H stretching manifolds of nucleic acid base pairs of adenosine and thymidine, incorporating a multitude of couplings with fingerprint and low-frequency modes.

Combined NMR and UV/vis spectroscopy in the solution state: study of the geometries of strong OHO hydrogen bonds of phenols with carboxylic acids.

It has become a routine approach in the structure determinations of organic compounds to employ a set of different methods, such as NMR, IR, Raman, UV/Vis spectroscopy and mass spectrometry, exploiting their complementary benefits. These experiments are usually performed using different samples prepared according to the specific requirements of the particular method. However, different samples of a given system may exhibit a different composition which can lead to a different degree of molecular aggregation and hence molecular conformations. The molecular conformations are temperature and solvent dependent and difficult to analyze. Thus, to ensure the compatibility of spectra obtained by different techniques, measurements performed on the same sample and under the same conditions may be crucial. For this reason, combined methods such as Raman spectroscopy/UV/ Vis spectroscopy/fluorescence spectroscopy, X-ray photoemission spectroscopy/ultraviolet photoemission spectroscopy/flame emission spectroscopy (XPS/UPS/FES), and EPR spectroscopy/UV/Vis spectroscopy/gas chromatography (GC) methods have been proposed. Recently, Hunger and co-workers have described a way to perform combined UV/ Vis absorption and magic-angle spinning (MAS) NMR measurements. This has incited us to combined low-temperature UV/Vis and solution-state NMR spectroscopy (UVNMR) which provides new insights into the acid–base chemistry of strongly hydrogen-bonded complexes dissolved in aprotic solvents. These systems are very sensitive to sample concentration, solvent, 9] and temperature. 9] The use of low-temperature NMR spectroscopy has the advantage that the regime of slow proton exchange between hydrogenbonded complexes can be reached, which allows their NMR parameters and hence information about their structure to be obtained. Moreover, it allows the influence of the solvent polarity which is strongly temperature dependent to be studied. The benefits of UVNMR will be demonstrated using the example of a phenol carboxylate complex dissolved in CD2Cl2. The reason to choose this system is two-fold. Firstly, previous UV/Vis studies indicated that the position of the absorption bands of phenol groups is sensitive to their protonation state, both in protic and aprotic 15] media; however, no information about hydrogen-bond geometries could be derived from UV/Vis measurements alone. Secondly, the UV/Vis spectra of solutions of a phenol with bases generally exhibit broad overlapping absorption bands indicating the presence of several species in different hydrogen bond and protonation states. Herein, we demonstrate that UVNMR allows the electronic excitation frequencies to be correlated with NMR chemical shifts which in turn provide information about hydrogen-bond geometries. To build a combined UVNMR probe an existing Bruker 5 mm low-temperature H–C probe was equipped with a guiding channel for the insertion of a fiber optic reflection probe. The optical probe with six illumination fibers and one read fiber was a custom variation of the regular probe with 200 mm fibers and 2.5 mm tip by Avantes (Eerbeek, Netherlands). In Figure 1, a schematic representation of the measurement region of the modified NMR probe is given. The tip of the optical probe is located centrally underneath the bottom of the NMR sample tube. The illumination fibers are connected to a halogen/deuterium light source (Avantes) and the light reflected to the read fiber is analyzed by a AvaSpec 2048 spectrometer (operating range 240–800 nm). Reflection of sufficient amounts of light is achieved by placing a polytetrafluoroethylene (PTFE) insert inside the sample tube, leaving only a thin layer of solution between the inner glass surface and the bottom of the insert (0.02–0.5 mm, depending on the shape of the insert; the “effective” optical path length can be estimated using solutions of a substance with known extinction coefficient). In this work, the PTFE

N-H stretching modes of adenosine monomer in solution studied by ultrafast nonlinear infrared spectroscopy and ab-initio calculations

The N-H stretching vibrations of adenine, one of the building blocks of DNA, are studied by combining infrared absorption and nonlinear two-dimensional infrared spectroscopy with ab initio calculations. We determine diagonal and off-diagonal anharmonicities of N-H stretching vibrations in chemically modified adenosine monomer dissolved in chloroform. For the single-quantum excitation manifold, the normal mode picture with symmetric and asymmetric NH(2) stretching vibrations is fully appropriate. For the two-quantum excitation manifold, however, the interplay between intermode coupling and frequency shifts due to a large diagonal anharmonicity leads to a situation where strong mixing does not occur. We compare our findings with previously reported values obtained on overtone spectroscopy of coupled hydrogen stretching oscillators.

Hydrogen Bond Geometries and Proton Tautomerism of Homoconjugated Anions of Carboxylic Acids Studied via H/D Isotope Effects on 13C NMR Chemical Shifts

Ten formally symmetric anionic OHO hydrogen bonded complexes, modeling Asp/Glu amino acid side chain interactions in nonaqueous environment (CDF(3)/CDF(2)Cl solution, 200-110 K) have been studied by (1)H, (2)H, and (13)C NMR spectroscopy, i.e. intermolecularly H-bonded homoconjugated anions of acetic, chloroacetic, dichloroacetic, trifluoroacetic, trimethylacetic, and isobutyric acids, and intramolecularly H-bonded hydrogen succinate, hydrogen rac-dimethylsuccinate, hydrogen maleate, and hydrogen phthalate. In particular, primary H/D isotope effects on the hydrogen bond proton signals as well as secondary H/D isotope effects on the (13)C signals of the carboxylic groups are reported and analyzed. We demonstrate that in most of the studied systems there is a degenerate proton tautomerism between O-H···O(-) and O(-)···H-O structures which is fast in the NMR time scale. The stronger is the proton donating ability of the acid, the shorter and more symmetric are the H-bonds in each tautomer of the homoconjugate. For the maleate and phthalate anions exhibiting intramolecular hydrogen bonds, evidence for symmetric single well potentials is obtained. We propose a correlation between H/D isotope effects on carboxylic carbon chemical shifts and the proton transfer coordinate, q(1) = ½(r(OH) - r(HO)), which allows us to estimate the desired OHO hydrogen bond geometries from the observed (13)C NMR parameters, taking into account the degenerate proton tautomerism.

Correlating Photoacidity to Hydrogen-Bond Structure by Using the Local O–H Stretching Probe in Hydrogen-Bonded Complexes of Aromatic Alcohols

To assess the potential use of O-H stretching modes of aromatic alcohols as ultrafast local probes of transient structures and photoacidity, we analyze the response of the O-H stretching mode in the 2-naphthol-acetonitrile (2N-CH3CN) 1:1 complex after UV photoexcitation. We combine femtosecond UV-infrared pump-probe spectroscopy and a theoretical treatment of vibrational solvatochromic effects based on the Pullin perturbative approach, parametrized at the density functional theory (DFT) level. We analyze the effect of hydrogen bonding on the vibrational properties of the photoacid-base complex in the S0 state, as compared to O-H stretching vibrations in a wide range of substituted phenols and naphthols covering the 3000-3650 cm(-1) frequency range. Ground state vibrational properties of these phenols and naphthols with various substituent functional groups are analyzed in solvents of different polarity and compared to the vibrational frequency shift of 2N induced by UV photoexcitation to the (1)Lb electronic excited state. We find that the O-H stretching frequency shifts follow a linear relationship with the solvent polarity function F0 = (2ε0 - 2)/(2ε0 + 1), where ε0 is the static dielectric constant of the solvent. These changes are directly correlated with photoacidity trends determined by reported pKa values and with structural changes in the O···N and O-H hydrogen-bond distances induced by solvation or photoexcitation of the hydrogen-bonded complexes.

NMR study of conformational exchange and double-well proton potential in intramolecular hydrogen bonds in monoanions of succinic acid and derivatives.

We present a (1)H, (2)H, and (13)C NMR study of the monoanions of succinic (1), meso- and rac-dimethylsuccinic (2, 3), and methylsuccinic (4) acids (with tetraalkylammonium as the counterion) dissolved in CDF(3)/CDF(2)Cl at 300-120 K. In all four monoanions, the carboxylic groups are linked by a short intramolecular OHO hydrogen bond revealed by the bridging-proton chemical shift of about 20 ppm. We show that the flexibility of the carbon skeleton allows for two gauche isomers in monoanions 1, 2, and 4, interconverting through experimental energy barriers of 10-15 kcal/mol (the process itself and the energy barrier are also reproduced in MP2/6-311++G** calculations). In 3, one of the gauche forms is absent because of the steric repulsion of the methyl groups. In all four monoanions, the bridging proton is located in a double-well potential and subject, at least to some extent, to proton tautomerism, for which we estimate the two proton positions to be separated by ca. 0.2 Å. In 1 and 3, the proton potential is symmetric. In 2, slowing the conformational interconversion introduces an asymmetry to the proton potential, an effect that might be strong enough even to synchronize the proton tautomerism with the interconversion of the two gauche forms. In 4, the asymmetry of the proton potential is due to the asymmetric substitution. The intramolecular H-bond is likely to remain intact during the interconversion of the gauche forms in 1, 3, and 4, whereas the situation in 2 is less clear.