Pi Hydrogen Research Articles

A C‐linked Glycomimetic in the Gas Phase and in Solution: Synthesis and Conformation of the Disaccharide Manα(1,6)‐C‐ManαOPh

The effect of carbon is subtle but sweet: The flexible C-linkage in the newly synthesised C-glycosyl mimetic, Manalpha(1,6)-C-ManalphaOPh allows OH--pi bonding, both in the gas phase and in aqueous solution. This interaction is absent in the O-linked disaccharide (see figure).The intrinsic conformational preference of a newly synthesised glycomimetic, the C-linked disaccharide Manalpha(1,6)-C-ManalphaOPh (1), has been determined in the gas phase at about 10 K by infrared ion dip spectroscopy coupled with density functional theory and ab initio calculations, and compared with its dynamical conformation in aqueous solution at 298 K by NMR spectroscopy. Comparisons are also made between these conformations and those of the corresponding O-linked disaccharide 2 in the gas phase and the C-linked disaccharide Manalpha(1,6)-C-ManalphaOMe (3) in the gas phase and in aqueous solution. The C- and O-linked disaccharides 1 and 2 present quite distinct conformational preferences in the gas phase: inter-glycosidic hydrogen bonding, seen in one of the two conformers populated in 2, is not seen in 1 which adopts a conformation (not populated in 2) with glycosidic dihedral angles (phi, psi, omega) of -72 degrees , 52 degrees and 66 degrees ; supported in part by an OH--pi hydrogen bond. This conformer is also strongly populated in an aqueous solution of 1 (and very weakly, of 3) together with a second conformer, with dihedral angles (phi, psi, omega) of about -60 degrees , 180 degrees and 60 degrees , not seen in the gas phase but by far the dominant conformer in an aqueous solution of 3. The C-disaccharide 1 was tested as a potential inhibitor, but displayed no significant inhibitory activity against Jack Bean alpha-mannosidase.

(2R,4S)-7-Bromo-2-phenyl-2,3,4,5-tetrahydro-1,4-epoxynaphtho[1,2-b]azepine, (2RS,4SR)-7-bromo-2-(4-chlorophenyl-2,3,4,5-tetrahydro-1,4-epoxynaphtho[1,2-b]azepine and (2RS,4SR)-2-(4-fluorophenyl)-2,3,4,5-tetrahydro-1,4-epoxynaphtho[1,2-b]azepine: hydrogen-bonded structures in two and three dimensions

(2R,4S)-7-Bromo-2-phenyl-2,3,4,5-tetrahydro-1,4-epoxynaphtho[1,2-b]azepine, C(20)H(16)BrNO, (I), exhibits evidence of a modest degree (ca 10%) of inversion twinning, while both (2RS,4SR)-7-bromo-2-(4-chlorophenyl)-2,3,4,5-tetrahydro-1,4-epoxynaphtho[1,2-b]azepine, C(20)H(15)BrClNO, (II), and (2RS,4SR)-2-(4-fluorophenyl)-2,3,4,5-tetrahydro-1,4-epoxynaphtho[1,2-b]azepine, C(20)H(16)FNO, (III), crystallize as genuine racemic mixtures. The molecules of (I) are linked into sheets by a combination of one C-H...O hydrogen bond and two C-H...pi(arene) hydrogen bonds, while those of (II) are linked into sheets of pi-stacked hydrogen-bonded chains. A combination of one C-H...O hydrogen bond and four independent C-H...pi(arene) hydrogen bonds links the molecules of (III) into a three-dimensional framework. The significance of this study lies in its finding, via comparison with the structures of some closely-related epoxybenzazepine analogues, of significant changes in crystal structures consequent upon small changes in the peripheral substituents.

Four 7-aryl-substituted pyrido[2,3-d]pyrimidine-2,4(1H,3H)-diones: similar molecular structures but different crystal structures

Molecules of 1,3-dimethyl-7-(4-methylphenyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione, C(16)H(15)N(3)O(2), (I), are linked by paired C-H...O hydrogen bonds to form centrosymmetric R(2)(2)(10) dimers, which are linked into chains by a single pi-pi stacking interaction. A single C-H...O hydrogen bond links the molecules of 7-(biphenyl-4-yl)-1,3-dimethylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione, C(21)H(17)N(3)O(2), (II), into C(10) chains, which are weakly linked into sheets by a pi-pi stacking interaction. In 7-(4-fluorophenyl)-3-methylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione, C(14)H(10)FN(3)O(2), (III), an N-H...O hydrogen bond links the molecules into C(6) chains, which are linked into sheets by a pi-pi stacking interaction. The molecules of 7-(4-methoxyphenyl)-3-methylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione, C(15)H(13)N(3)O(3), (IV), are also linked into C(6) chains by an N-H...O hydrogen bond, but here the chains are linked into sheets by a combination of two independent C-H...pi(arene) hydrogen bonds.

Competition between π and σ hydrogen bonds and conformational probing of 2-orthofluorophenylethanol by low-and high-resolution electronic spectroscopy

The flexible model molecule 2-orthofluorophenylethanol has been investigated by laser-induced fluorescence, and low- and high-resolution resonance-enhanced two-photon ionization spectroscopy in combination with high-level ab initio quantum chemistry calculations. One dominant conformation has been identified in the cold molecular beam corresponding to the most stable theoretically predicted gauche structure stabilized by an intramolecular OH...pi hydrogen bond. A tentative assignment of a higher-lying gauche conformer present in the molecular beam separated by high potential barriers from the most stable one has been made. The missing other higher-energy theoretically predicted conformations most likely relax to the most stable ones during the process of the adiabatic expansion. The good agreement between the experimental and theoretical results demonstrates that even in the case of a substitution with an electronegative atom at the ortho position, bringing about a significant redistribution of the electron density in the benzene ring and providing a convenient binding site for the formation of a competing OH...F sigma hydrogen bond, the nonclassical OH...pi bond remains the preferred binding motif for the most stable conformer.

Tracing dynamic self-disassociation behavior of pyrrole with novel T-shaped hydrogen bonding

Near infrared spectroscopy (NIR) and two-dimensional correlation spectroscopy (2Dcos) were employed to study the dynamic self-disassociation behavior of hydrogen bonds in neat liquid pyrrole during heating. Two regions (7000-6430 cm(-1) for NH-related vibrational overtones and 6200-6100 cm(-1) for CH-related vibrational overtones and combination modes) are the focus of this paper, whose integral absorption temperature dependence exhibited a continuous convex variation. Two-dimensional correlation analysis has discerned the sequence of change of different aggregated species of pyrrole. Additionally, we carefully investigated the band shift phenomenon of N-H...pi hydrogen bonding in pyrrole dimers, and assigned this band shift as the result of the transformation of pyrrole dimers from T-shaped geometry to antiparallel geometry.

Mass analysed threshold ionisation spectroscopy of flexible 2-para-fluorophenylethanol conformers with and without an intramolecular OH⋯π bond

The cationic state of the prototype flexible molecule 2-para-fluorophenylethanol has been investigated by combination of mass-analysed threshold-ionisation (MATI) spectroscopy and quantum chemistry ab initio density functional theory (DFT) calculations employing two different functionals: the B3LYP functional and the new hybrid functional M05. The MATI spectra measured via vibronic bands in the S1 intermediate state belonging to the most stable gauche conformer stabilised by an intramolecular OH...pi hydrogen bond are structureless, while the spectra recorded via bands of the anti conformer feature well-resolved peaks. This result is in a good accord with our theoretical predictions showing that upon ionisation, the anti conformer retains its structure, while the lowest-energy gauche conformer undergoes a significant structural change resulting in a break of the OH...pi bond. This and the good agreement between the measured band positions and the theoretically predicted frequencies for the cationic anti conformer confirm the conformational assignment. The result for the cation provides clear evidence for the existence of a nonclassical intramolecular OH...pi hydrogen bond if the electron density in the aromatic ring is sufficiently high as is the case only for the neutral molecule.

A theoretical study on unusual intermolecular T-shaped X–H...π interactions between the singlet state HB=BH and HF, HCl, HCN or H2C2

The unusual T-shaped X-H...pi hydrogen bonds are found between the B=B double bond of the singlet state HB=BH and the acid hydrogen of HF, HCl, HCN and H2C2 using MP2 and B3LYP methods at 6-311++G(2df,2p) and aug-cc-pVTZ levels. The binding energies follow the order of HB=BH...HF>HB=BH...HCl>HB=BH...HCN>HB=BH...H2C2. The hydrogen-bonded interactions in HB=BH...HX are found to be stronger than those in H2C=CH2...HX and OCB identical withBCO...HX. The analyses of natural bond orbital (NBO) and the electron density shifts reveal that the nature of the T-shaped X-H...pi hydrogen-bonded interaction is that much of the lost density from the pi-orbital of B=B bond is shifted toward the hydrogen atom of the proton donor, leading to the electron density accumulation and the formation of the hydrogen bond. The atoms in molecules (AIM) theory have also been applied to characterize bond critical points and confirm that the B=B double bond can be a potential proton acceptor.

FourN7-alkoxybenzyl-substituted 4,5,6,7-tetrahydro-1H-pyrazolo[3,4-b]pyridine-5-spiro-1′-cyclohexane-2′,6′-diones: hydrogen-bonded supramolecular structures in zero, one, two or three dimensions

3-tert-Butyl-7-(4-methoxybenzyl)-4',4'-dimethyl-1-phenyl-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-b]pyridine-5-spiro-1'-cyclohexane-2',6'-dione, C(31)H(37)N(3)O(3), (I), 3-tert-butyl-7-(2,3-dimethoxybenzyl)-4',4'-dimethyl-1-phenyl-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-b]pyridine-5-spiro-1'-cyclohexane-2',6'-dione, C(32)H(39)N(3)O(4), (II), 3-tert-butyl-4',4'-dimethyl-7-(3,4-methylenedioxybenzyl)-1-phenyl-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-b]pyridine-5-spiro-1'-cyclohexane-2',6'-dione, C(31)H(35)N(3)O(4), (III), and 3-tert-butyl-4',4'-dimethyl-1-phenyl-7-(3,4,5-trimethoxybenzyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-b]pyridine-5-spiro-1'-cyclohexane-2',6'-dione ethanol 0.67-solvate, C(33)H(41)N(3)O(5) x 0.67C(2)H(6)O, (IV), all contain reduced pyridine rings having half-chair conformations. The molecules of (I) and (II) are linked into centrosymmetric dimers and simple chains, respectively, by C-H...O hydrogen bonds, augmented only in (I) by a C-H...pi hydrogen bond. The molecules of (III) are linked by a combination of C-H...O and C-H...pi hydrogen bonds into a chain of edge-fused centrosymmetric rings, further linked by weak hydrogen bonds into supramolecular arrays in two or three dimensions. The heterocyclic molecules in (IV) are linked by two independent C-H...O hydrogen bonds into sheets, from which the partial-occupancy ethanol molecules are pendent. The significance of this study lies in its finding of a very wide range of supramolecular aggregation modes dependent on rather modest changes in the peripheral substituents remote from the main hydrogen-bond acceptor sites.

Hydrogen-bonded chains of rings in 3-tert-butyl-1-phenyl-7-(4-trifluoromethylbenzyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-b]pyridine-5-spiro-1′-cyclohexane-2′,6′-dione and 3-tert-butyl-7-(4-methoxybenzyl)-1-phenyl-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-b]pyridine-5-spiro-1′-cyclohexane-2′,6′-dione

In each of 3-tert-butyl-1-phenyl-7-(4-trifluoromethylbenzyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-b]pyridine-5-spiro-1'-cyclohexane-2',6'-dione, C(29)H(30)F(3)N(3)O(2), (I), and 3-tert-butyl-7-(4-methoxybenzyl)-1-phenyl-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-b]pyridine-5-spiro-1'-cyclohexane-2',6'-dione, C(29)H(33)N(3)O(3), (II), the reduced pyridine ring adopts a half-chair conformation. The molecules of compound (I) are linked by two C-H...O hydrogen bonds to form a C(5)C(5)[R(1)(2)(8)] chain of rings, while in compound (II), two C-H...O hydrogen bonds link the molecules into a C(6)C(7)[R(2)(2)(11)] chain of rings, which is further reinforced by a C-H...pi hydrogen bond. The significance of this study lies in its observation of significant differences in hydrogen-bonded structures consequent upon very minor changes in remote substituents.

Structure-Directed Reversion in the π-Facial Stereoselective Alkylation of Chiral Bicyclic Lactams

The reversal of the pi-facial diastereoselectivity observed in the benzyl bromide alkylation of the enolate of phenylglycinol-derived oxazolopiperidone is examined by means of theoretical calculations and experimental assays. When the angular carbon adopts an R configuration, the endo addition is intrinsically favored due to the lower torsional strain induced in the TS, but for the reaction with benzyl bromide, which affords the exo product. This reversal is attributed to the formation of a C-H...pi hydrogen bond between the C-H unit of the C8a angular position and the benzene ring of the alkylating reagent. A similar secondary interaction explains the stereochemical reversion observed in the benzyl alkylation of the enolate of oxazolopyrrolidinone. These findings point out that the delicate balance between factors that dictate the diastereoselectivity in the alkylation of chiral byciclic lactams can be unexpectedly altered by weak secondary interactions. The results presented here provide valuable guidelines to tune the selective preparation of enantiopure bioorganic and pharmaceutical compounds.

The basicity of unsaturated hydrocarbons as probed by hydrogen-bond-acceptor ability: bifurcated N-H+ ...pi hydrogen bonding.

The competitive substitution of the anion (A(-)) in contact ion pairs of the type [Oct3NH+]B(C6F5)4 (-) by unsaturated hydrocarbons (L) in accordance with the equilibrium Oct3NH+...A(-) + nL right arrow over left arrow [Oct3NH+...Ln]A(-) has been studied in CCl4. On the basis of equilibrium constants, K, and shifts of nuNH to low frequency, it has been established that complexed Oct3NH...+Ln cations with n=1 and 2 are formed and have unidentate and bifurcated N--H+...pi hydrogen bonds, respectively. Bifurcated hydrogen bonds to unsaturated hydrocarbons have not been observed previously. The unsaturated hydrocarbons studied include benzene and methylbenzenes, fused-ring aromatics, alkenes, conjugated dienes, and alkynes. From the magnitude of the redshifts in the N--H stretching frequencies, Delta nuNH, a new scale for ranking the pi basicity of unsaturated hydrocarbons is proposed: fused-ring aromatics<or=benzene<toluene<xylene<mesitylene<durene<conjugated dienes approximately 1-alkynes<pentamethylbenzene<hexamethylbenzene<internal alkynes approximately cycloalkenes<1-methylcycloalkenes. This scale is relevant to the discussion of pi complexes for incipient protonation reactions and to understanding N--H+...pi hydrogen bonding in proteins and molecular crystals.

Three tetrahydro-1,4-epoxy-1-benzazepines carrying pendent heterocyclic substituents: supramolecular structures in zero, one or two dimensions

(2SR,4RS)-7-Fluoro-2-exo-(2-furyl)-2,3,4,5-tetrahydro-1H-1,4-epoxy-1-benzazepine, C(14)H(12)FNO(2), (I), crystallizes with Z' = 2 in the space group P2(1)/c. A combination of three C-H...O hydrogen bonds and one C-H...N hydrogen bond links the molecules into a complex chain of rings, and pairs of such chains are linked into a tube-like structure by two C-H...pi(arene) hydrogen bonds. There are no hydrogen bonds in the structure of racemic (2SR,4RS)-2-exo-(5-bromo-2-thienyl)-7-fluoro-2,3,4,5-tetrahydro-1H-1,4-epoxy-1-benzazepine, C(14)H(11)BrFNOS, (II), while the molecules of (2S,4R)-2-exo-(5-bromo-2-thienyl)-7-trifluoromethoxy-2,3,4,5-tetrahydro-1H-1,4-epoxy-1-benzazepine, C(15)H(14)BrF(3)NO(2)S, (III), are linked into sheets by a combination of two C-H...O hydrogen bonds and one C-H...pi(arene) hydrogen bond. The significance of this study lies in its observation of the wide variation in the patterns of supramolecular aggregation, consequent upon modest changes in the peripheral substituents.

2-tert-Butyl-5-methyl-7,8-dihydro-6H-cyclopenta[e]pyrazolo[1,5-a]pyrimidine: molecular stacks built from C—H...π(pyrazole) hydrogen bonds and π–π stacking interactions

In the title compound, C(14)H(19)N(3), the bond distances within the heterocyclic portion of the molecule indicate incomplete pi delocalization. The molecules are linked into stacks by a combination of two C-H...pi(pyrazole) hydrogen bonds and two independent pi-pi stacking interactions between inversion-related pyrimidine rings. The significance of this study lies in its observation of significant differences in both molecular conformation and supramolecular aggregation between the title compound, an example of a 2-alkylpyrazolo[1,5-a]pyrimidine, and some analogous 2-arylpyrazolo[1,5-a]pyrimidines.

A centrosymmetric polymorph of chloridotris(triphenylphosphine-κP)copper(I) at 150 K

This study characterizes a new polymorph of the title compound, [CuCl(C18H15P)3], and analyses the influence of the extensive network of weak hydrogen-bonding interactions in the generation of this different crystal structure. The compound crystallizes in the centrosymmetric space group C2/c with two crystallographically independent molecules per asymmetric unit, in contrast with the previously determined polymorph which crystallizes in the noncentrosymmetric space group P3 with three crystallographically independent molecules in the asymmetric unit, each with crystallographically imposed C3 symmetry [Gill, Mayerle, Welcker, Lewis, Ucko, Barton, Stowens & Lippard (1976). Inorg. Chem. 15, 1155-1168]. The geometries of the two molecules of the title compound are very similar, with each having an approximately tetrahedral coordination around the central Cu atom and approximate C(s) molecular symmetry. The molecules pack in chains parallel to the crystallographic b axis, connected by C-H...Cl and C-H...pi(phenyl) hydrogen bonds.

Superperiodic Assembly of 2,6-Diethynylpyridine through Weak Hydrogen Bonds at the 1-Phenyloctane/HOPG Interface

Regardless of the absence of alkyl chains and conventional hydrogen bonding sites as well as its small size, 2,6-diethynylpyridine forms an ordered array at the interface between 1-phenyloctane and highly oriented pyrolytic graphite (HOPG) under room temperature conditions, as revealed by scanning tunneling microscopy. We propose a model for the superperiodic molecular arrangement with reference to the bulk crystal structure, in which the surface pattern is governed by weak C-H...N and C-H...pi hydrogen bonds as well as the periodic potential of the underlying graphite surface.

Structure of the Phenylacetylene−Water Complex as Revealed by Infrared-Ultraviolet Double Resonance Spectroscopy

The structure of the phenylacetylene-water complex has been elucidated based on spectral shifts in electronic and vibrational transitions. Phenylacetylene forms a cyclic complex with water incorporating C-H...O and O-H...pi hydrogen bonds, which is different from both the benzene-water and acetylene-water complexes, even though phenylacetylene combines the features of both benzene and acetylene. Formation of such a complex can be rationalized on the basis of cooperativity between the two sets of hydrogen bonds.

Hydrogen-bonded chains of rings in 1-(4-chloroanilinomethyl)-5-(4-chlorophenyl)-1,3,5-triazinane-2-thione and hydrogen-bonded sheets in 1-anilinomethyl-5-phenyl-1,3,5-triazinane-2-thione

In 1-(4-chloroanilinomethyl)-5-(4-chlorophenyl)-1,3,5-triazinane-2-thione, C(16)H(16)Cl(2)N(4)S, there are two independent molecules in the asymmetric unit which form inversion dimers via two weak N-H...S hydrogen bonds. The dimers are then linked into C(9)C(14) chains by a C-H...S hydrogen bond and a C-H...Cl contact. In 1-(anilinomethyl)-5-phenyl-1,3,5-triazinane-2-thione, C(16)H(18)N(4)S, molecules are linked into complex sheets via a combination of N-H...S and C-H...pi hydrogen bonds.

N–H⋯π interactions in pyrroles: systematic trends from the vibrational spectroscopy of clusters

Pyrrole and some of its methylated derivatives are aggregated in a controlled way in pulsed supersonic jet expansions. The cluster N-H stretching dynamics is studied using FTIR and Raman spectroscopy. Dimers, trimers and tetramers can be differentiated. Systematic trends in the dimer N-H...pi interaction as a function of methyl substitution are identified and explored for predictions. Overtone jet absorption spectroscopy is used to extract anharmonicities for the N-H bond in different environments. The N-H anharmonicity constant increases by 10% upon dimerization. Bulk matrix shifts can be emulated by the formation of Ar-decorated clusters. The experimental results are expected to serve as benchmarks for an accurate ab initio characterization of the N-H...pi hydrogen bond.

8-tert-Butyl-7-(4-chlorophenyl)-10-phenyl-5,6-dihydro-10H-benzo[h]pyrazolo[3,4-b]quinoline

The title compound, C(30)H(26)ClN(3), crystallizes with Z' = 3 in the P\overline{1} space group. The three independent molecules have very similar, although not identical, conformations, with almost perfect screw-boat forms adopted by the non-aromatic carbocyclic rings. Four independent C-H...pi(arene) hydrogen bonds link the molecules into centrosymmetric six-component aggregates.

Conformation-Specific Spectroscopy and Photodissociation of Cold, Protonated Tyrosine and Phenylalanine

We present here ultraviolet and infrared spectra of protonated aromatic amino acids in a cold, 22-pole ion trap. Ultraviolet photofragmentation spectra of protonated tyrosine and phenylalanine show vibronically resolved bands corresponding to different stable conformers: two for PheH+ and four in the case of TyrH+. We subsequently use the resolved UV spectra to perform conformer-specific infrared depletion spectroscopy. Comparison of the measured infrared spectra to density functional theory calculations helps assign the geometry of the various conformers, all of which exhibit NH...pi hydrogen bonds and NH...O=C interactions, with the COOH group oriented either anti or gauche to the aromatic ring. In both molecules the majority of the observed fragments result from dissociation on an excited electronic state. In TyrH+, different conformers excited with practically the same energy exhibit different fragmentation patterns, suggesting that the excited-state dynamics depend upon conformation.