Protonation Sites in Gaseous Pyrrole and Imidazole: A Neutralization–Reionization and ab initio Study

Mild gas-phase acids C₄H₉⁺ and NH₄⁺ protonate pyrrole at C-2 and C-3 but not at the nitrogen atom, as determined by deuterium labeling and neutralization–reionization mass spectrometry. Proton affinities in pyrrole are calculated by MP2/6–311G(2d, p) as 866, 845 and 786 kJ mol^-1 for protonation at C-2, C-3 and N, respectively. Vertical neutralization of protonated pyrrole generates bound radicals that in part dissociate by loss of hydrogen atoms. Unimolecular loss of hydrogen atom from C-2-and C-3-protonated pyrrole cations is preceded by proton migration in the ring. Protonation of gaseous imidazole is predicted to occur exclusively at the N-3 imine nitrogen to yield a stable aromatic cation. Proton affinities in imidazole are calculated as 941, 804, 791, 791 and 724 for the N-3, C-4, C-2, C-5 and N-1 positions, respectively. Radicals derived from protonated imidazole are only weakly bound. Vertical neutralization of N-3-protonated imidazole is accompanied by large Franck–Condon effects which deposit on average 183 kJ mol^-1 vibrational energy in the radicals formed. The radicals dissociate unimolecularly by loss of hydrogen atom, which involves both direct N-H bond cleavage and isomerization to the more stable C-2 H-isomer. Potential energy barriers to isomerizations and dissociations in protonated pyrrole and imidazole isomers and their radicals were investigated by ab initio calculations.     

Etude Conformationnelle par Résonance Magnétique Nucléaire Protonique des Dérivés de la O-Isopropylidène-2′,3′ Adénosine

Conformational analysis using ¹H n.m.r. data (δ, ³J and NOE) has been carried out on several derivatives of 2′,3′,-O-isopropylideneadenosine bearing various substituents at positions C-5′, C-8 and N-6. Conformational modifications are assigned to specific interactions between the sugar and purine moieties and also to solvent effects.     

Proton transfer at the carboxylic sites of amino acids: A single water molecule catalyzed process

Ab initio calculations at MP2 level of theory were used to study the proton transfer at the carboxylic sites of amino acids, in the isolated, mono‐ and di‐hydrated forms. In the case of water dimer, two interaction modes with glycine neutral structures (see Fig. 3 ) were explored, corresponding to the concerted and stepwise reaction pathways. Their transition states can be described as (H₂O? H? OH₂)⁺ [Fig. 4 (a)] and (H₂O‐‐‐H? OH₂)⁺ [Fig. 4 (b)], respectively. The energy analysis indicated that the concerted pathway is preferred. In the isolated, mono‐ and di‐hydrated glycine complexes, the activation barriers of the proton transfer at the carboxylic sites were calculated to be 34.49, 16.59, and 13.36 kcal mol^?1, respectively. It was thus shown that the proton transfer is significantly assisted and catalyzed by water monomer so that it can take place at room temperature. Instead, the further addition of water molecules plays solvent effects rather than catalytic effects to this proton transfer process. The above results obtained with discrete water molecules were supported by the solvent continuum calculated data. It was also observed that the heavy dependence of the solvent continuum models on dipole moments may produce misleading results. © 2008 Wiley Periodicals, Inc. Int J Quantum Chem, 2009     

Benzo- and indoloquinolizine derivatives. VI—configuration and conformation of 4b,5,6,7,8,8a,10,11,16,16b-decahydrodibenz[f,h]indolo[2,3-a]quinolizine diastereoisomers. A 270 MHz 1H NMR study

The synthesis of a D/E cis isomer of the title compound is described. In an attempt to obtain the other D/E cis isomer, epimerisation reactions were studied. The configuration and conformation of the isomers are determined on the basis of their ¹H NMR spectra. The shift of the 16b proton on N-9 protonation indicates the quinolizidine conformation. At 270 MHz, the ABCD system of the C-10 and C-11 methylenes can be analysed. The ²J(C-10H₂), together with the multiplicity of H-8a, allows an unequivocal assignment of a cis-anti-cis structure to the only D/E cis isomer obtained.     

Negative Ion CID Fragmentation of <Emphasis Type="Italic">O-</Emphasis>linked Oligosaccharide Aldoses—Charge Induced and Charge Remote Fragmentation

Collision induced dissociation (CID) fragmentation was compared between reducing and reduced sulfated, sialylated, and neutral O-linked oligosaccharides. It was found that fragmentation of the [M – H]^– ions of aldoses with acidic residues gave unique Z-fragmentation of the reducing end GalNAc containing the acidic C-6 branch, where the entire C-3 branch was lost. This fragmentation pathway, which is not seen in the alditols, showed that the process involved charge remote fragmentation catalyzed by a reducing end acidic anomeric proton. With structures containing sialic acid on both the C-3 and C-6 branch, the [M – H]^– ions were dominated by the loss of sialic acid. This fragmentation pathway was also pronounced in the [M – 2H]^2– ions revealing both the C-6 Z-fragment plus its complementary C-3 C-fragment in addition to glycosidic and cross ring fragmentation. This generation of the Z/C-fragment pairs from GalNAc showed that the charges were not participating in their generation. Fragmentation of neutral aldoses showed pronounced Z-fragmentation believed to be generated by proton migration from the C-6 branch to the negatively charged GalNAc residue followed by charge remote fragmentation similar to the acidic oligosaccharides. In addition, A-type fragments generated by charge induced fragmentation of neutral oligosaccharides were observed when the charge migrated from C-1 of the GalNAc to the GlcNAc residue followed by rearrangement to accommodate the ^0,2A-fragmentation. LC-MS also showed that O-linked aldoses existed as interchangeable α/β pyranose anomers, in addition to a third isomer (25% of the total free aldose) believed to be the furanose form.     

Hydrates and ammonium salts of 4-nitrobenzenesulfonic acid: supramolecular organization and its relation to proton conductivity

Structural features, the crystal packing, and the proton conductivity of a series of hydrates and ammonium salts of 4-nitrobenzenesulfonic acid were studied. It was shown that infinite cation associates containing the onium moiety are responsible for a substantial increase in the proton conductivity. The nature of the disorder in a series of crystals was investigated by performing X-ray diffraction studies at different temperatures. A new type of structural synthons, viz., anion-anion dimers stabilized by the SO₃ ⁻…NO₂ interaction, was found and characterized and the role of solvent water molecules was elucidated based on high-resolution X-ray diffraction data. The water molecules serve mainly as channels for charge transfer from the cation to the anion with retention of the electroneutrality.     

17O NMR spectroscopy: Proton–oxygen coupling in simple alcohols at natural abundance

¹⁷O NMR data are reported for 3-pentanol ( 1 ), cyclopentanol ( 2 ), cyclohexanol ( 3 ), and cycloheptanol ( 4 ). The ¹⁷O NMR signals for 1–4 appeared as doublets, shown to arise from proton–oxygen coupling (¹J_OH = 76 ± 3 Hz) by proton decoupling experiments. The effect of concentration, temperature, and solvent was examined in detail for 2 . Proton—oxygen coupling was observed at low concentrations, decreased at lower temperatures, and was sensitive to solvent.     

Symmetrization of Cationic Hydrogen Bridges of Protonated Sponges Induced by Solvent and Counteranion Interactions as Revealed by NMR Spectroscopy

The properties of the intramolecular hydrogen bonds of doubly ¹⁵N‐labeled protonated sponges of the 1,8‐bis(dimethylamino)naphthalene (DMANH⁺) type have been studied as a function of the solvent, counteranion, and temperature using low‐temperature NMR spectroscopy. Information about the hydrogen‐bond symmetries was obtained by the analysis of the chemical shifts δ_H and δ_N and the scalar coupling constants J(N,N), J(N,H), J(H,N) of the ¹⁵NH¹⁵N hydrogen bonds. Whereas the individual couplings J(N,H) and J(H,N) were averaged by a fast intramolecular proton tautomerism between two forms, it is shown that the sum |J(N,H)+J(H,N)| generally represents a measure of the hydrogen‐bond strength in a similar way to δ_H and J(N,N). The NMR spectroscopic parameters of DMANH⁺ and of 4‐nitro‐DMANH⁺ are independent of the anion in the case of CD₃CN, which indicates ion‐pair dissociation in this solvent. By contrast, studies using CD₂Cl₂, [D₈]toluene as well as the freon mixture CDF₃/CDF₂Cl, which is liquid down to 100 K, revealed an influence of temperature and of the counteranions. Whereas a small counteranion such as trifluoroacetate perturbed the hydrogen bond, the large noncoordinating anion tetrakis[3,5‐bis(trifluoromethyl)phenyl]borate B[{C₆H₃(CF₃)₂}₄]^? (BARF^?), which exhibits a delocalized charge, made the hydrogen bond more symmetric. Lowering the temperature led to a similar symmetrization, an effect that is discussed in terms of solvent ordering at low temperature and differential solvent order/disorder at high temperatures. By contrast, toluene molecules that are ordered around the cation led to typical high‐field shifts of the hydrogen‐bonded proton as well as of those bound to carbon, an effect that is absent in the case of neutral NHN chelates.     

Intramolecular Hydrogen Bonding In N-(2-Amino-2-Deoxy-β-D-Glucopyranoside)-N'-Carbamoyl-L-Dipeptidylesters: An Infrared And 1H Nmr Study

ABSTRACT

Ten N-(2-amino-2-deoxy-β-D-glucopyranoside)-N'-carbamoyl-L-dipeptidylesters with different amino acid sequences in the dipeptide unit were studied by means of IR and ¹H NMR spectroscopy. In the IR spectra three bands at 3453, 3420 and 3390 cm^-1 were observed which could be assigned to the free NH, the intramolecularly hydrogen bonded NH species forming five-membered, C₅, and seven-membered, C₇, rings, respectively. Comparing the NH band positions which correspond to the C₇ rings of the Gly-Xaa and the Xaa-Gly dipeptidylesters, the signals of the Xaa-Gly sequence were shifted by 10 cm^-1 to lower wave numbers indicating stronger hydrogen bonds. The temperature effect dv/dT was an order of magnitude larger for the C₇ associates than for C₅ showing the highest enthalpy of the C₇ hydrogen bond. The ¹H NMR spectra give three separate signals for the NH groups. The temperature coefficient ?δ/?T was the largest for N-1-H indicating the formation of less stable hydrogen bonds (C₇). The solvent induced changes of the chemical shift of the NH signals was lowest for the N-3-H signal. Obviously the deshielding properties on this function do not vary in dependence of the solvent polarity. The hydrogen/deuterium exchange rate was lowest for the N-6-H proton indicating the lower accessibility of this proton. Combining the results of both spectroscopic methods it can be concluded that the N-1-H forms only C₇ rings whereas N-6-H can participate in C₅ and C₇ intramolecular hydrogen bonds. The strength of the formed C₇ associates depends on the amino acid sequence in the dipeptide residue.     

13C NMR spectroscopy of [4.n.0] bicyclic compounds: Assignment of the ring junction configuration from ring junction configuration from ring junction 13C chemical shifts—application and limits

Several 6-methyl-9-carbamoyltetrahydro-4H-pyrido[1,2-α]pyrimidin-4-ones have been prepared using phosgene iminium chloride. These compounds can exist in equilibrium as the cis (3A) imine ? (3B) enamine ? trans (3C) imine. ¹H, ¹³C and ¹⁵N NMR prove that the cis- and trans-imine isomers are predominant in the equilibrium. ¹H NMR data reveal that the share of the 3B enamine form is negligible at measurable concentrations. The isomeric ratio 3A:3C is time dependent and can be monitored by measuring the CH₃? C-6 and (CH₃)₂N signals. The ¹³C NMR data show that doublets in the range 42–45 ppm for C-9 are only compatible with the imine forms 3A and 3C. The SCS values of the CH₃? C-6 and OCN(CH₃)₂ groups were calculated and used for identification of the cis and trans isomers. ¹⁵N NMR data show that the N-1 chemical shift of the imine is approximately ? 140 ppm for compound 3, whereas that of a fixed enamine is around ? 267.8. This provides additional support for the predominance of the imine tautomers in the equilibrium 3A ? 3B ? 3C. ¹⁵N data allow the stereoisomers 3A and 3C to be distinguished.     

Use of solvent isotope effect to identify an intermediate carbanion in the β-elimination reactions from N-[2-(4-pyridyl)ethyl]quinuclidinium and N-[2-(2-pyridyl)ethyl]quinuclidinium induced by acetohydroxamate/acetohydroxamic acid buffers

Solvent isotope effect is a useful technique for identifing and characterizing an intermediate carbanion in the base-induced -elimination reaction from N-[2-(4-pyridyl)ethyl]quinuclidinium, 1, and N-[2-(2-pyridyl)ethyl]quinuclidinium, 2. While at high [buffer]k _obs(D₂O) > k _obs(H₂O) due to the presence of a primary kinetic solvent isotope effect on the reprotonation of the intermediate carbanion by BD, at low [buffer] no solvent isotope effect is observed, and k _obs(D₂O) k _obs(H₂O). The data are in agreement with a reversible E1cb mechanism in which carbon deprotonation occurs from NH⁺, the substrate protonated at the nitrogen atom of the pyridine ring. In the absence of solvent isotope effect at low [buffer], and with the similarity of the results obtained with the two isomers, 1 and 2, the significance of an intramolecular proton transfer in the intermediate carbanion can be excluded in these processes.     

SCF LCGO MO studies on the fluoronium ion FH 2 + and its hydrogen bonding interaction with hydrogen fluoride FH

The stability and geometrical structure of the fluoronium ion is investigated using the onedeterminant SCF LCAO MO method. The equilibrium geometry is characterized by a bond length of d(FH)=0.95 Å and a bond angle of 114.75°. The proton binding energy is determined to be 120.1 kcal/mole. The molecules FH ₃ ²⁺ and FH₃ are found to be unstable. A binding energy of 30.7 kcal/mole is obtained for the hydrogen bond formation between the systems FH ₂ ⁺ and FH. In the minimum energy structure the central proton is situated midway between the two F atoms in a symmetrical single minimum potential. The general behavior of the potential curves of the di-solvated proton involving NH₃, OH₂, and FH as solvent molecules is discussed. In all these cases double minimum potentials are found, if the equilibrium separation between the heavy atoms is larger than approximately 2.4 Å, and single minimum potential for separations smaller than this value.     

Solvent effects upon the proton NMR linewidth in dimethylformamide

The NMR linewidth of the formyl proton in dimethylformamide has been studied in the neat liquid and twelve organic solvents. It varies by more than one order of magnitude which is referred to solvent viscosity changes and to the protonation of dimethylformamide. The data do not allow the distinction between N- and O-protonation without further knowledge of the solvent dependence of either the nitrogen-14 spin lattice relaxation time or the spin-spin coupling ²J(NH).     

Proton dissociation and transfer in hydrated phosphoric acid clusters

The dynamics and mechanisms of proton dissociation and transfer in hydrated phosphoric acid (H₃PO₄) clusters under excess proton conditions were studied based on the concept of presolvation using the H₃PO₄–H₃O⁺–nH₂O complexes (n = 1–3) as the model systems and ab initio calculations and Born–Oppenheimer molecular dynamics (BOMD) simulations at the RIMP2/TZVP level as model calculations. The static results showed that the smallest, most stable intermediate complex for proton dissociation (n = 1) is formed in a low local‐dielectric constant environment (e.g., ε = 1), whereas proton transfer from the first to the second hydration shell is driven by fluctuations in the number of water molecules in a high local‐dielectric constant environment (e.g., ε = 78) through the Zundel complex in a linear H‐bond chain (n = 3). The two‐dimensional potential energy surfaces (2D‐PES) of the intermediate complex (n = 1) suggested three characteristic vibrational and ¹H NMR frequencies associated with a proton moving on the oscillatory shuttling and structural diffusion paths, which can be used to monitor the dynamics of proton dissociation in the H‐bond clusters. The BOMD simulations over the temperature range of 298–430 K validated the proposed proton dissociation and transfer mechanisms by showing that good agreement between the theoretical and experimental data can be achieved with the proposed rate‐determining processes. The theoretical results suggest the roles played by the polar solvent and iterate that insights into the dynamics and mechanisms of proton transfer in the protonated H‐bond clusters can be obtained from intermediate complexes provided that an appropriate presolvation model is selected and that all of the important rate‐determining processes are included in the model calculations. © 2015 Wiley Periodicals, Inc.     

Analysis and applications of 13C NMR lanthanide induced shifts of 1,4-benzodiazepines

Lanthanide induced shifts using Yb(fod)₃ and Pr(fod)₃ were used for the signal assignments of the ¹³C spectra of the 1,4-benzodiazepines diazepam, desmethyldiazepam, prazepam and flurazepam, and for characterizing their solution conformation with respect to the substituents at N-1 and C-5. The phenyl substituent at C-5 is found to be nearly coplanar with the π-bond between C-5 and N-4, and the substituents at N-1 seem to be orientated towards the carbonyl group with dihedral angles of either 60° or 120° between the bonds N-1 and C-2 and C-12 and C-13. The metal ions seem to bind to O-2 with metal-oxygen distances between 0.19 and 0.26 nm and bond angles between 117° and 167°. Contact shifts induced by Pr(fod)₃ are slightly larger than obtained for Yb(fod)₃, whereas the latter reagent causes a stronger broadening.     

Nuclear magnetic resonance and stereochemistry of vincamone

The stereochemistry in solution of vincamone was deduced by proton magnetic resonance using the paramagnetic shifts reagent Eu(fod)₃. The lanthanide induced shift computer simulation suggests that, at room temperature, the indole group is nearly planar, the rings C and E assume the envelope conformation with N-4 and C-16 as flaps, the ring D is in the chair one and the ethyl side chain prefers a trans position with respect to C-15.     

A 13C-NMR spectral study of cellulose and glucopyranose dissolved in the NH3/NH4SCN solvent system

The ¹³C-NMR chemical shifts of a cellulose with a DP_w of 23 dissolved in the NH₃/NH₄SCN solvent system were found to be very similar to those of cellulose dissolved in DMSO (cellulose oligomers), in the LiCl/DMAC system and in the N-methylmorpholine N-oxide/DMSO system. It was concluded from this that cellulose does not react with the NH₃/NH₄SCN solvent. It was found, however, that glucose reacts with the solvent at C-1 to form β-D -glucopyranosy-lamine. Separation of this compound from the solvent resulted in another compound which was determined to be β,β-di-D -glucopyranosylamine. The compounds β-D -glucopyranosylamine, N-acetyl-2,3,4,6-tetra-O-acetyl-β-D -glucopyranosylamine, β,β-di-D -glucopyranosylamine, α,β-di-D -glucopyranosylamine, 2,3,4,6,2′,3′,4′,6′-octa-O-acetyl-α,β-di-D -glucopyranosylamine were all synthesized and the ¹³C-NMR chemical shifts of these compounds are reported. It was also found that for the low-DP cellulose sample which was used the reducing end group existed and had reacted with the solvent to form an amine at C-1.     

Unravelling the Reaction Mechanism for the Fast Photocyclisation of 2‐Benzoylpyridine in Aqueous Solvent by Time‐Resolved Spectroscopy and Density Functional Theory Calculations

A combined femtosecond transient absorption (fs‐TA) and nanosecond time‐resolved resonance Raman (ns‐TR³) spectroscopic investigation of the photoreaction of 2‐benzoylpyridine (2‐BPy) in acetonitrile and neutral, basic and acidic aqueous solvents is reported. fs‐TA results showed that the nπ* triplet 2‐BPy is the precursor of the photocyclisation reaction in neutral and basic aqueous solvents. The cis triplet biradical and the cis singlet zwitterionic species produced during the photocyclisation reaction were initially characterised by ns‐TR³ spectroscopy. In addition, a new species was uniquely observed in basic aqueous solvent after the decay of the cis singlet zwitterionic species and this new species was tentatively assigned to the photocyclised radical anion. The ground‐state conformation of 2‐BPy in acidic aqueous solvent is the pyridine nitrogen‐protonated 2‐BPy cation (2‐BPy‐NH⁺) rather than the neutral form of 2‐BPy. After laser photolysis, the singlet excited state (S₁) of 2‐BPy‐NH⁺ is generated and evolves through excited‐state proton transfer (ESPT) and efficient intersystem crossing (ISC) processes to the triplet exited state (T₁) of the carbonyl oxygen‐protonated 2‐BPy cation (2‐BPy‐OH⁺) and then photocyclises with the lone pair of the nitrogen atom in the heterocyclic ring. Cyclisation reactions take place both in neutral/basic and acidic aqueous solvents, but the photocyclisation mechanisms in these different aqueous solvents are very different. This is likely due to the different conformation of the precursor and the influence of hydrogen‐bonding of the solvent on the reactions.     

Nitrogen-15 n.m.r. studies of 13C, 15N labeled arginine

¹⁵N n.m.r. spectra of [¹³C-2, 3-¹⁵N₂-guanidino]arginine and [¹³C, ¹⁵N₂] urea were obtained in D₂O and H₂O at a variety of pH values both with and without proton decoupling. The effects of the proton exchange rate are readily observable in the proton coupled ¹⁵N spectra. When the guanidino group is deprotonated (pK = 12.5), the terminal nitrogens give a single resonance 6.6 ppm downfield of the protonated species, indicating a rapid tautomeric exchange. The observed NH and CN couplings are compared with calculated values, and good agreement is found for ¹J(CN) using a Blizzard–Santry type calculation. The ramifications of the proton exchange on ¹⁵N n.m.r. spectra of amino acids and peptides are discussed.