Three-center Hydrogen Research Articles

Molecular Structure of Complexes with Bifurcated Hydrogen Bond: I. N-(4-Methyl-2-nitrophenyl)acetamide

According to the results of HF/6-31G* and B3LYP/6-31G* nonempirical calculations, N-(4-methyl- 2-nitrophenyl)acetamide in the synperiplanar and antiperiplanar conformations gives stable complexes with protophilic solvents, which are stabilized by bifurcated (three-center) hydrogen bond. The complexes are characterized by (1) opposite variations of the interatomic distances and angles corresponding to intra- and intermolecular components of the bifurcated hydrogen bond, (2) extension of the intramolecular component and a more pronounced shortening of the intermolecular component with increase in the strength of the three-center H-complex, and (3) nonlinear and nonmonotonic relation between the NH stretching vibration frequency and the energy of complex formation.

UV resonance Raman and circular dichroism studies of a DNA duplex containing an A(3)T(3) tract: evidence for a premelting transition and three-centered H-bonds.

The presence of A(n) and A(n)T(n) tracts in double-helical sequences perturbs the structural properties of DNA molecules, resulting in the formation of an alternate conformation to standard B-DNA known as B'-DNA. Evidence for a transition occurring prior to duplex melting in molecules containing A(n) tracts was previously detected by circular dichroism (CD) and calorimetric studies. This premelting transition was attributed to a conformational change from B'- to B-DNA. Structural features of A(n) and A(n)T(n) tracts revealed by X-ray crystallography include a large degree of propeller twisting of adenine bases, narrowed minor grooves, and the formation of three-centered H-bonds between dA and dT bases. We report UV resonance Raman (UVRR) and CD spectroscopic studies of two related DNA dodecamer duplexes, d(CGCAAATTTGCG)(2) (A(3)T(3)) and d(CGCATATATGCG)(2) [(AT)(3)]. These studies address the presence of three-centered H-bonds in the B' conformation and gauge the impact of these putative H-bonds on the structural and thermodynamic properties of the A(3)T(3) duplex. UVRR and CD spectra reveal that the premelting transition is only observed for the A(3)T(3) duplex, is primarily localized to the dA and dT bases, and is associated with base stacking interactions. Spectroscopic changes associated with the premelting transition are not readily detectable for the sugar-phosphate backbone or the cytosine and guanosine bases. The temperature-dependent concerted frequency shifts of dA exocyclic NH(2) and dT C4=O vibrational modes suggest that the A(3)T(3) duplex forms three-centered hydrogen bonds at low temperatures, while the (AT)(3) duplex does not. The enthalpy of this H-bond, estimated from the thermally induced frequency shift of the dT C4=O vibrational mode, is approximately 1.9 kJ/mol or 0.46 kcal/mol.

D-Phenylglycinium perchlorate

In the title compound, C8H10NO2+·ClO4−, the phenyl­glycinium cation is linked to the perchlorate anion through a normal O—H⋯O [2.78 (2) A] hydrogen bond. The phenyl­glycinium cation and perchlorate anion are also held together by N—H⋯O hydrogen bonds. Chelated three-centered hydrogen bonds are observed involving the amino-N atom and the perchlorate-O atoms. The molecular aggregation of the hydro­philic zone at z = 1 \over 4 is sandwiched between two hydro­phobic zones.

β-Alaninium perchlorate

In the title compound, C3H8NO2+·ClO4−, a normal O—H⋯O hydrogen bond is observed which forms a dimer between the carboxyl­ic acid groups of two β-alaninium residues related by an inversion center. An intramolecular hydrogen bond is observed between the amino-N and carboxyl-O atoms. The amino-N atom is also involved in a three-centered hydrogen bond with O atoms of the perchlorate anion across the center of inversion, forming infinite chains.

Stable three-center hydrogen bonding in a partially rigidified structure.

The three-center hydrogen bond in diaryl amide 1 was examined by IR and 1H NMR spectroscopy, X-ray crystallography, and ab initio calculations. By comparing 1 with its structural isomers 2, 3 and 4, and with its conformational isomers 1a-c, it was found that the two two-center components of the three-center interaction reinforce each other, that is, the enhanced stability of the three-center hydrogen bond is a result of positive cooperativity between the two components. Substituents not involved in hydrogen bonding have little effect on the strength of the two- and three-center hydrogen bonds. To our knowledge, this is the first three-center hydrogen-bonding system that has been shown to exhibit positive cooperativity. Ab initio calculations of the geometries, vibrational modes, and 1H NMR chemical shifts also support the experimental findings. These results have provided a new insight into the three-center intramolecular hydrogen bonding in a partially rigidified structure and have provided a reliable motif for designing stably folded structures.

Synthesis, Stereochemistry, and Spin Transition of Heterometal Dinuclear Fe(II)–Cr(III) Complex Bridged by 3,5-Bis(pyridin-2-yl)-pyrazolate

Abstract We have synthesized and characterized a new heterometal dinuclear complex, [(nta)CrIII(μ-bpypz)FeII(picen)]BF4 (1), where nta = nitritotriacetate; bpypz− =3,5-bis(pyridin-2-yl)-pyrazolate; and picen = N,N′-bis-(2-pyridylmethyl)ethylenediamine. The X-ray structure of the Fe(II)–Cr(III)·H2O·3dmf demonstrated that this has a dinuclear structure with a highly distorted octahedron around a high-spin Fe(II) and intramolecular bifurcated three-centered hydrogen bonds between the carboxylate oxygens of the nta and an amine proton of the picen with an abnormal conformation. A magnetic susceptibility measurement and/or the Mössbauer spectra of 1 substantiated a gradual spin-transition from 130 K to 300 K in a heating process centered around 250 K with a small hysteresis dip in the Fe(II) complex. The spin-transition temperature of 1 is lower than that of the mononuclear complex, [FeII(picen)(Hbpypz)](BF4)2(2), resulting from the weaker ligand field of 1 with a distorted octahedron than that of 2.

Energetics and cooperativity in three-center hydrogen bonding interactions. II. Intramolecular hydrogen bonding systems

High level ab initio calculations have been carried out on a number of intramolecular two- and three-center H-bonding structures containing the amide motif, NHC=O. These structures serve as model systems for probing the stability of intramolecular three-center H bonds of the type A1HA2. Particular attention is given to cooperative effects in the three-center H-bonding structures. A systematic assessment of cooperativity for intramolecular H-bonding systems is presented.

Energetics and cooperativity in three-center hydrogen bonding interactions. I. Diacetamide-X dimers (X=HCN, CH3OH)

High level ab initio calculations are carried out on diacetamide–X (DA–X) dimers, X=HCN, CH3OH. The dimers are used as model systems to investigate the energetics and cooperative phenomomena in intermolecular three-center hydrogen-bond (H-bond) interactions relative to two-center H-bond interactions. The trans–trans conformer of diacetamide is chosen as a suitable model for intermolecular three-center H bonding where one H atom is interacting with two acceptor atoms. The proton–acceptor atoms are rigidly held in the same molecule. For both model systems, it is found that the calculated interaction energy per H bond is appreciably smaller in the three-center than in the two-center H-bond dimers, suggesting possibly a general characteristic of intermolecular three-center H bonds, namely, a negative cooperativity. More importantly, it is found that frequency shifts, intensity factors, bond lengths, and H1 nuclear magnetic resonance chemical shifts all support the energetic calculations in that the intermolecular three-center H-bond dimers exhibit marked negative cooperative effects. Despite the negative cooperativity, the three-center DA–HCN dimer is actually energetically favorable over the two-center counterpart, whereas the three-center DA–CH3OH dimer is energetically unfavorable over the two-center counterpart.

The first example of coexistence of the ketoamino–enolimino forms of diamine Schiff base naphthaldimine parts: the crystal and molecular structure of N,N′-bis(1-naphthaldimine)-o-phenylenediamine chloroform (1/1) solvate at 200 K

The N,N′-bis(1-naphthaldimine)-o-phenylenediamine chloroform (1/1) solvate was prepared from 2-hydroxy-1-naphthaldehyde and 1,2-phenylenediamine in a 2:1 molar ratio and characterized in solution and in the solid state using X-ray single crystal diffractometry, IR and NMR spectroscopy.The structure consists of three structural fragments: two planar, but not coplanar naphthaldimine moieties linked by phenyl ring that derived from o-phenylenediamine. The naphthaldimine fragments contain, along with naphthalene rings, six-membered pseudoaromatic chelate rings, formed by OH⋯N or NH⋯O intramolecular hydrogen bonds that retain planarity of the aldimine fragments.This structure is the first example of the coexistence of two different hydrogen bond types within Schiff base molecule, i.e. the one naphthaldimine part exists in the enolimino form (OH⋯N hydrogen bond of 2.5487(17) Å), while the other exists in the ketoamino form (NH⋯O hydrogen bond of 2.5706(19) Å). The different hydrogen bond types are related to the different π-electron density distribution within two parts. The amino hydrogen atom forms three-center intramolecular hydrogen bond, which includes the NH⋯O hydrogen bond of 2.5706(19) Å within the ketoamino part and also the NH⋯N bond of 2.7238(18) Å linking two naphthaldimine fragments of the molecule. IR and 1H and 13C NMR spectral data are consistent with revealed molecular structure in the solid state.

Hydrogen bonding: part 78. Ab initio molecular orbital study of intra- and intermolecular hydrogen bonding in choline and betaine and their compounds with HF and H2O

We previously prepared several compounds of the zwitterions [(CH3)3NCH2CH2O]0 (deprotonated choline, herein named cholaine) and [(CH3)3NCH2CO2]0 (betaine) and proposed structures based on infrared spectroscopy. We now examine these compounds with use of ab initio molecular orbital methods to further elucidate possible structure. These calculations demonstrate that: (1) cholaine and betaine both have internal CHO hydrogen bonds, and these are retained in some form in all other compounds. (2) Cholaine hydrate and hydrofluoride and betaine hydrofluoride monomers have covalent three-center hydrogen bonds between H2O or HF and negative zwitterion oxygen, and additional CHX hydrogen bonds to H2O oxygen or HF fluorine. (3) Cholaine monohydrate and cholaine hydrofluoride monohydrate form dimers of Ci symmetry which contain planar C2h (H2O·O)2 and (HOH·F)2 clusters. (4) Cholaine hydrofluoride forms head-to-tail dimers bound by intermolecular CHX hydrogen bonds; this arrangement could lead to extended linear structures in the solid state. (5) Betaine hydrofluoride, in contrast, forms a tightly bound discrete dimeric unit in which two molecules join in a head-to-head manner held together by five intermolecular hydrogen bonds and by the mutual proximities of negative fluorides to positive nitrogens.

L-Argininium dinitrate

In the title compound, C6H16N4O22+·2NO3 −, the diprotonated argininium mol­ecule is linked by a strong O—H⋯O [2.653 (7) A] hydrogen bond to the nitrate anion. The single-bonded O atom of the carboxyl group exhibits a very unusual cis conformation with respect to the α-amino N atom. Chelated three-centered hydrogen bonds are observed in the case of the Nα and N∊ atoms with the nitrate anions. The argininium mol­ecules are connected by type A, B and D interactions through nitrate anions.

Hydrogen Bonding in Chloroform Solutions of Ethylenedioxy Ethers. Spectroscopic Evidence of Bifurcated Hydrogen Bonds

Chloroform solutions of 1,4-dioxane, 1,2-dimethoxyethane, and diethylene glycol dimethyl ether were studied by means of IR absorption spectroscopy. The intensity of the C−D stretching band of a small amount of deuterated chloroform added to the solutions was used as a probe of the strength of hydrogen bonding between the ethers and chloroform. A two-component model, which assumes that the chloroform molecules can be classified as hydrogen bonded and non-hydrogen bonded, was used to interpret the variations of the intensity of the C−D stretching band on changing the concentration of chloroform. In the frame of this model, the hydrogen bonding was considered as a chemical reaction between the lone electron pairs of the ether oxygens and the chloroform molecules. As a result, the equilibrium constant of hydrogen bonding was estimated and the stoichiometry of the hydrogen bonded complexes of ethers and chloroform was revealed. It was found that the lone electron pairs of the ether oxygens do not participate equally well in hydrogen bonding with chloroform, most probably because of steric hindrance. The analysis of the experimental results also suggested that chloroform can form strong bifurcated hydrogen bonds with the neighboring oxygens of the open-chain ethers. The bifurcated three-centered hydrogen bonds were confirmed by ab initio molecular orbital calculations.

Solvatochromism of Heteroaromatic Compounds: VII. Bifurcate Hydrogen Bond in Solvatochromic Complexes of 2-(1,2,2-Tritricyanovinyl)pyrrole

IR and UV spectrosocopy and quantum chemistry were used to reveal a bifurcate (three-center) hydrogen bond in the complexes of 2-(1,2,2-tricyanovinyl)pyrrole with hydrogen-bond acceptors. In the gas phase and aprotic inert solvents this compound exists predominantly as the sp conformer stabilized by intra- molecular hydrogen bond involving an orthogonal π system of the nitrile group and the NH hydrogen. The formation of the three-center hydrogen bond with an aprotic protophilic solvent shifts the conformational equilibrium to the ap conformer. As the strength of the intermolecular hydrogen bond increases in the series nitromethane < acetonitrile < dioxane, the fraction of the ap conformer increases and becomes prevailing already in the moderately protophilic THF. Solvatochromism of the long-wave absorption band in the elec- tronic spectra of the sp and ap conformers was studied in detail.

Solvatochromism of Heteroaromatic Compounds: VIII. 2-(Tricyanovinyl)-5-phenylpyrrole

Rotational isomerism of 2-(tricyanovinyl)-5-phenylpyrrole and formation of complexes with a three-centered (bifurcational) hydrogen bond were studied by UV spectroscopy and quantum-chemical calculations. In the gas phase and in weakly and moderately protophilic media these compounds have mainly the syn-periplanar form stabilized by the intramolecular hydrogen bond involving the orthogonal π system of the nitrile group and the NH hydrogen atom. No intermolecular H complex is formed in such solvents. In tetrahydrofuran, cyclohexanone, pyridine, and some other media a complex conformational equilibrium is observed. Interaction with aliphatic alcohols, amides, dimethyl sulfoxide, and triethylamine results in stabilization of the H complex of the anti-periplanar conformer.

Cyclic dithiophosphate salts [Et3NH+[(OCH2CMe2CH2O)P(S)S]− and [Et3NH]+[CH2{6-t-Bu-4-Me-C6H4O}2P(S)S

X-ray structures of the cyclic dithiophosphate salts [Et3NH]+[(OCH2CMe2CH2O)P(S)(S)]− (1) and [Et3NH]+[CH2{6-t-Bu-4-Me-C6H4O}2P(S)S]− (2) have been determined. Crystal data for 1: Tetragonal, P42/m, a = 13.416(7), b = 13.416(2), c = 9.153(2) A, and Z = 4. Crystal data for 2 = Monoclinic, P21/c, a = 19.1112(17), b = 14.649(9), c = 22.7166(19) A, β = 102.883(7)°, and Z = 8. The six- and eight-membered rings in 1 and 2 have chair and boat-chair conformations respectively. Both of these compounds show weak N—H······S hydrogen bonds; interestingly, in 2 both two-center and three-center hydrogen bonds are observed in the solid state.

Anomalous stereochemistry of pyrazolato-3,5-dicarboxylato-bridged dinuclear chromate(III) complexes containing ethylenediamine-N,N'-dicarboxylates with entrapped unstable conformations: X-ray structure of Na[Cr2(eddp)(mu-pzdc)].6H2O.

Several new pyrazolato-3,5-dicarboxylato (pzdc) bridged dinuclear chromate(III) complexes containing linear tetradentate O-N-N-O type ligands were synthesized and structurally characterized. Among them, the X-ray structure of the eddp complex Na[Cr2(eddp)(mu-pzdc)].6H2O (eddp = ethylenediamine-N,N'-dipropionate) was determined to have a (sym-cis)-(unsym-cis) geometrical configuration with intramolecular three-center hydrogen bonds, entrapping the unfavored sym-cis configuration for the Cr(eddp) moiety as well as the favored unsym-cis one. As a pair of positional disorders, there were also found to be two conformational isomers with respect to the absolute configurations of the coordinated asymmetric nitrogen atom at the G (in-plane) ring for the unsym-cis moiety. Moreover, chiral pzdc-bridged dinuclear complexes with another type of O-N-N-O ligand, 1,2-cyclohexanediamine-N,N'-diacetate (cdda), were successfully synthesized, isolated, and characterized by column chromatographic behavior, elemental analysis, and chiroptical spectra. There were two diastereomers for Na[(R,R-cdda)Cr(mu-pzdc)Cr(S,S-cdda)] and only one isomer for Na[(R,R-cdda)Cr(mu-pzdc)Cr(R,S-cdda)] and Na[(R,R-cdda)Cr(mu-pzdc)Cr(edda)] (R,R- or S,S- and R,S-cdda = R,R-trans- or S,S-trans- and R,S-cis-1,2-cyclohexanediamine-N,N'-diacetate, and edda = ethylenediamine-N,N'-diacetate). From their circular dichroism (CD) spectra, these complexes could exhibit the delta-delta absolute configuration with ((sym-cis-R,R-cdda)-(unsym-cis-edda or S,S- or R,S-cdda)) geometrical configuration, indicating the abnormal eq-eq (N-Ceq) configuration for the R,R-cdda. The comparison among the CD spectra of the ((cdda)-(cdda)) complexes revealed that two diastereomers of the ((R,R-cdda)-(S,S-cdda)) complex correspond to the conformational isomers resulting from the difference in geometrical orientations of the secondary amine protons on two coordinated asymmetric nitrogen atoms with the opposite absolute configuration in the unsym-cis-S,S-cdda moiety. In a series of the pzdc-bridged Cr(III) complexes the anomalous conformations in two different geometrical configurations could be entrapped probably owing to stereognostic coordination through the intramolecular N-H...O hydrogen bond interaction.

Molecular structure and activity toward DNA of baicalein, a flavone constituent of the Asian herbal medicine "Sho-saiko-to".

Baicalein (5,6,7-trihydroxyflavone, 1) is of interest because of its broad spectrum of biological activity. It is a constituent of the east Asian herbal remedy, "Sho-saiko-to". The 3D structure of 1 was determined using X-ray diffraction. The compound exists in an almost planar conformation with a C-2-C-1' bond distance of 1.476(5) A. Hydrogen-bonding interactions predominate in the crystal structure. The position of the three hydroxyl groups maximizes intramolecular hydrogen bonding, and each of the hydroxyl hydrogen atoms is a donor in a three-center hydrogen bond. The carbonyl oxygen, O-4, is an acceptor in an intramolecular hydrogen bond (with OH-5). Two molecules of 1 exist as hydrogen-bonded dimers related by inversion center (-x + 1, -y, -z + 1). O-4 is also an acceptor in an intermolecular hydrogen bond with OH-6. The planarity of the flavone framework is dependent on structural and/or electronic forces that stabilize the negative charge on the exocyclic oxygen atom, O-4. Compound 1, therefore, is planar in any situation where forces can stabilize the negative charge on O-4. Consistent with this, UV absorbance studies performed on 1-DNA complexes with varying concentrations of 1 strongly suggest intercalation of 1 within the double helix, followed by possible interstrand cross-links.

Hydrogen bonding. Part 75. Infrared, titrametric and molecular orbital study of the structure, solubility and reaction with fluoride ion of 2,3-dicarboxypyrazine

2,3-Dicarboxypyrazine (2,3-H2DCPz), unlike 2,3-dicarboxypyridine (2,3-H2DCPy), does not exist as a zwitterion in the solid state. This is due to the remarkably low base strength of nitrogen in the pyrazine ring relative to that of pyridine. The decrease in the base strength of pyrazine relative to pyridine may result from greater disruption of the aromatic π-system of pyrazine on protonation than is the case with pyridine. We propose that 2,3-H2DCPz has a structure of Cs symmetry in the solid state in which one carboxyl group forms an internal hydrogen bond to carbonyl of adjacent carboxyl in the same molecule, and the second carboxyl forms an intermolecular hydrogen bond to carbonyl in an adjacent molecule. The monoanion in 2,3-NaHDCPz has a strong O–H–O covalent three-center hydrogen bond between carboxylate groups. When saturated solutions of 2,3-H2DCPz are treated with F−, one additional diacid molecule is taken into solution for each 1.5 F− added. As is the case with 2,3-H2DCPy, the high solubility and acid strength of 2,3-H2DCPz (pKa=2.87) leads to formation of the hydrogen-rich H2F3− ion instead of HF2−.

Mechanism of RNase T 1: concerted triester-like phosphoryl transfer via a catalytic three-centered hydrogen bond

Background: The microscopic events of ribonuclease (RNase) catalyzed phosphoryl transfer reactions are still a matter of debate in which the contenders adhere to either the classical concerted acid–base mechanism or a more sequential triester-like mechanism. In the case of RNase A, small thio-effects of the nonbridging oxygens have been invoked in favor of the classical mechanism. However, the RNase T 1 catalyzed transphosphorylation of phosphorothioate RNA is highly stereoselective. R P thio-substituted RNA is depolymerized 60 000 times faster than S P thio-substituted RNA by this enzyme, whereas the uncatalyzed cleavage of both substrates occurs at comparable rates. We combined site-directed mutagenesis in the RNase active site and stereospecific thio-substitution of an RNA substrate to probe the intermolecular interactions of the enzyme with the nonbridging pro- S P oxygen that bring about this stereoselectivity of RNase T 1. Results: Thio-substitution of the nonbridging pro- S P oxygen in the substrate afflicts chemical turnover but not ground state binding whereas thio-substitution of the nonbridging pro- R P oxygen does not affect the kinetics of RNase T 1. Site-directed mutagenesis of the catalytic base Glu58 impairs the enzyme’s ability to discriminate both phosphorothioate diastereomers. Glu58Ala RNase T 1 cleaves R P and S P phosphorothioate RNA with similar rates. The dependence of the pro- S P thio-effect on the presence of the Glu58 carboxylate evidences a strong rate-limiting interaction between the nonbridging pro- S P oxygen and the catalytic base Glu58 in the wild type enzyme. Conclusions: Based on these results, we put forward a new triester-like mechanism for the RNase T 1 catalyzed reaction that involves a three-centered hydrogen bond between the 2′-OH group, the nonbridging pro- S P oxygen and one of the carboxylate oxygens of Glu58. This interaction allows nucleophilic attack on an activated phosphate to occur simultaneously with general base catalysis, ensuring concerted phosphoryl transfer via a triester-like mechanism.

“N-Fused Porphyrin”: A New Tetrapyrrolic Porphyrinoid with a Fused Tri-pentacyclic Ring

The syntheses and X-ray structures of novel porphyrinoids, “N-fused porphyrins (NFPs)”, and their reactivity were described. NFP was spontaneously produced from the bromo-substituted N-confused tetraarylporphyrin in a pyridine solution at room temperature. X-ray diffraction analyses revealed that the porphyrinoid core containing a fused tri-pentacyclic ring is almost planar. The deviation from the mean plane of 4e‘, for example, was within 0.30 Å. The peripheral aryl substituents were tilted 50.4, 53.5, 64.4, and 12.4° relative to the porphyrin mean plane, respectively. The occurrence of a three-centered hydrogen bonding in the NFP core was inferred by the downfield shift of the inner NH signal (e.g., 8.48 ppm for 4e‘) in 1H NMR and the short distances (within 2.4−2.9 Å) among the inner core nitrogens, N2, N3, and N4. The optical absorption spectra of NFPs exhibit Soret-like transitions around 360, 500, and 550 nm and weak Q-like bands around 650, 700, 850, and 940 nm in CH2Cl2. The electrode process of 4e‘ showed the first oxidation at 0.08 V and reduction at −1.37 V (vs Fc/Fc+), which suggested the small energy gap attributed to the unusual long-wavelength absorption was mainly due to the rising of the HOMO energy level. The first-order rate constants (kf) for the transformation from NCPs to NFPs were largely affected by the substituents at the meso position, showing a good correlation with Hammet σ+ parameters. Moreover, the reverse reaction from NFPs to NCPs was observed in the CH2Cl2 solution by treating with a base. Dynamic ring inversion in the tetrapyrrolic porphyrin core is discussed.