Intramolecular Hydrogen Bridge Research Articles

Comprehensive Empirical Model of Substitution-Influence on Hydrogen Bonding in Aromatic Schiff Bases.

In this work, over 500 structures of tri-ring aromatic Schiff bases with different substitution patterns were investigated to develop a unified description of the substituent effect on the intramolecular hydrogen bridge. Both proximal and distal effects were examined using Density Functional Theory (DFT) in the gas phase and with solvent reaction field (Polarizable Continuum Model (PCM) and water as the solvent). In order to investigate and characterize the non-covalent interactions, a topological analysis was performed using the Quantum Theory of Atoms In Molecules (QTAIM) theory and Non-Covalent Interactions (NCI) index. The obtained results were summarized as the generalized, empirical model of the composite substituent effect, assessed using an additional group of simple ring-based Schiff bases. The composite substituent effect has been divided into separate increments describing the different interactions of the hydrogen bridge and the substituent: the classical substituent effect, involving resonance and induction mediated through the ring, steric increment based on substituent proximity to the bridge elements, and distal increment, derived from substitution on the distal ring.

How Substitution Combines with Non-Covalent Interactions to Modulate 1,4-Naphthoquinone and Its Derivatives Molecular Features-Multifactor Studies.

Substitution is well-known to modulate the physico-chemical properties of molecules. In this study, a combined, multifactor approach was employed to determine a plethora of substitution patterns using –Br and –O-H in 1,4-naphthoquinone and its derivatives. On the basis of classical Density Functional Theory (DFT), 25 models divided into three groups were developed. The first group contains 1,4-naphthoquinone and its derivatives substituted only by –Br. The second group consists of compounds substituted by –Br and one –O-H group. As a result of the substitution, an intramolecular hydrogen bond was formed. The third group also contains –Br as a substituent, but two –O-H groups were introduced and two intramolecular hydrogen bonds were established. The simulations were performed at the B97XD/6-311++G(2d,2p) level of theory. The presence of substituents influenced the electronic structure of the parent compound and its derivatives by inductive effects, but it also affected the geometry of the 2 and 3 groups, due to the intramolecular hydrogen bonding and the formation of a quasi-ring/rings. The static DFT models were applied to investigate the aromaticity changes in the fused rings based on the Harmonic Oscillator Model of Aromaticity (HOMA). The OH stretching was detected for the compounds from groups 2 and 3 and further used to find correlations with energetic parameters. The evolution of the electronic structure was analyzed using Hirshfeld atomic charges and the Substituent Active Region (cSAR) parameter. The proton reaction path was investigated to provide information on the modulation of hydrogen bridge properties by diverse substitution positions on the donor and acceptor sides. Subsequently, Car–Parrinello Molecular Dynamics (CPMD) was carried out in the double-bridged systems (group 3) to assess the cooperative effects in double –O-H-substituted systems. It was determined that the –O-H influence on the core of the molecule is more significant than that of –Br, but the latter has a major impact on the bridge dynamics. The competitive or synergic effect of two –Br substituents was found to depend on the coupling between the intramolecular hydrogen bridges. Thus, the novel mechanism of a secondary (cooperative) substituent effect was established in the double-bridged systems via DFT and CPMD results comparison, consisting of a mediation of the bromine substitutions’ influence by the cooperative proton transfer events in the hydrogen bridges.

Non-Covalent Forces in Naphthazarin—Cooperativity or Competition in the Light of Theoretical Approaches

Non-covalent interactions responsible for molecular features and self-assembly in Naphthazarin C polymorph were investigated on the basis of diverse theoretical approaches: Density Functional Theory (DFT), Diffusion Quantum Monte Carlo (DQMC), Symmetry-Adapted Perturbation Theory (SAPT) and Car-Parrinello Molecular Dynamics (CPMD). The proton reaction paths in the intramolecular hydrogen bridges were studied. Two potential energy minima were found indicating that the proton transfer phenomena occur in the electronic ground state. Diffusion Quantum Monte Carlo (DQMC) and other levels of theory including Coupled Cluster (CC) employment enabled an accurate inspection of Potential Energy Surface (PES) and revealed the energy barrier for the proton transfer. The structure and reactivity evolution associated with the proton transfer were investigated using Harmonic Oscillator Model of Aromaticity - HOMA index, Fukui functions and Atoms In Molecules (AIM) theory. The energy partitioning in the studied dimers was carried out based on Symmetry-Adapted Perturbation Theory (SAPT) indicating that dispersive forces are dominant in the structure stabilization. The CPMD simulations were performed at 60 K and 300 K in vacuo and in the crystalline phase. The temperature influence on the bridged protons dynamics was studied and showed that the proton transfer phenomena were not observed at 60 K, but the frequent events were noticed at 300 K in both studied phases. The spectroscopic signatures derived from the CPMD were computed using Fourier transformation of autocorrelation function of atomic velocity for the whole molecule and bridged protons. The computed gas-phase IR spectra showed two regions with OH absorption that covers frequencies from 2500 cm to 2800 cm at 60 K and from 2350 cm to 3250 cm at 300 K for both bridged protons. In comparison, the solid state computed IR spectra revealed the environmental influence on the vibrational features. For each of them absorption regions were found between 2700–3100 cm and 2400–2850 cm at 60 K and 2300–3300 cm and 2300–3200 cm at 300 K respectively. Therefore, the CPMD study results indicated that there is a cooperation of intramolecular hydrogen bonds in Naphthazarin molecule.

Highly Selective Ortho-Directed Dicarboxylation of Cyclopentadiene by Methylcarbonates and CO2 or COS - First Insight into Co-ordination Chemistry of New Ambident Ligands.

This research presents the highly regioselective syntheses of 1,2‐dicarboxylated cyclopentadienide salts [Cat]2[C5H3(CO2)2H] by reaction of a variety of organic cation methylcarbonate salts [Cat]OCO2Me (Cat=NR4 +, PR4 +, Im+) with cyclopentadiene (CpH) or by simply reacting organic cation cyclopentadienides Cat[Cp] (Cat=NR4 +, PR4 +, Im+) with CO2. One characteristic feature of these dianionic ligands is the acidic proton delocalized in an intramolecular hydrogen bridge (IHB) between the two carboxyl groups, as studied by 1H NMR spectroscopy and XRD analyses. The reaction cannot be stopped after the first carboxylation. Therefore, we propose a Kolbe‐Schmitt phenol‐carboxylation related mechanism where the acidic proton of the monocarboxylic acid intermediate plays an ortho‐directing and CO2 activating role for the second kinetically accelerated CO2 addition step exclusively in ortho position. The same and related thiocarboxylates [Cat]2[C5H3(COS)2H] are obtained by reaction of COS with Cat[Cp] (Cat=NR4 +, PR4 +, Im+). A preliminary study on [Cat]2[C5H3(CO2)2H] reveals, that its soft and hard coordination sites can selectively be addressed by soft Lewis acids (Mo0, Ru2+) and hard Lewis acids (Al3+, La3+).

Study of the polymorphic states of chloral hydrate by 35Cl NQR relaxometry

In this article the results of an experimental study of the molecular crystal of chloral hydrate in α - and β -forms by 35Cl NQR relaxometry method with using of inverse Laplace transformation are presented. The results indicate the presence of intramolecular hydrogen bridge bonds of two chlorine atoms of C-Cl3 groups with hydrogen of hydroxyl groups. An analysis of the spin-lattice relaxation times shows that the mobility of all chlorine atoms increases upon the transition from the unstable β - form of chloral hydrate to the stable α – form.

The Intramolecular Hydrogen Bond N-H···S in 2,2'-Diaminodiphenyl Disulfide: Experimental and Computational Thermochemistry.

The intramolecular hydrogen bond of the N-H···S type has been investigated sparingly by thermochemical and computational methods. In order to study this interaction, the standard molar enthalpies of formation in gaseous phase of diphenyl disulfide, 2,2'-diaminodiphenyl disulfide and 4,4'-diaminodiphenyl disulfide at T = 298.15 K were determined by experimental thermochemical methods and computational calculations. The experimental enthalpies of formation in gas-phase were obtained from enthalpies of formation in crystalline phase and enthalpies of sublimation. Enthalpies of formation in crystalline phase were obtained using rotatory bomb combustion calorimetry. By thermogravimetry, enthalpies of vaporization were obtained, and by combining them with enthalpies of fusion, the enthalpies of sublimation were calculated. The Gaussian-4 procedure and the atomization method were applied to obtain enthalpies of formation in gas-phase of the compounds under study. Theoretical and experimental values are in good agreement. Through natural bond orbital (NBO) analysis and a topological analysis of the electronic density, the intramolecular hydrogen bridge (N-H···S) in the 2,2'-diaminodiphenyl disulfide was confirmed. Finally, an enthalpic difference of 11.8 kJ·mol-1 between the 2,2'-diaminodiphenyl disulfide and 4,4'-diaminodiphenyl disulfide was found, which is attributed to the intramolecular N-H···S interaction.

Effect of intramolecular hydrogen bonding of α, ω–diamines on the structure and exchange affinity of 18–crown–6-amine host-guest complexes in gas phase: A collision cross section measurements by ion mobility spectrometry

The effect of intramolecular hydrogen bonding on the thermodynamics of the host–guest interactions have been investigated through the gas phase exchange studies of protonated normal primary amines and α,ω–diamines with ammonium ion in 18–crown–6 (18C6) cavity using ion mobility spectrometry (IMS). The cross sectional areas were calculated for α, ω–diamines and normal primary amines in free and complex form. The results showed that protonated α, ω–diamines have more compact structure than that of the protonated normal primary amines in the free forms. This is attributed to the formation of intramolecular hydrogen bridges in protonated α, ω–diamines. In addition, we found that 18C6 attachment prevents from the formation of intramolecular hydrogen bond in α, ω–diamines. The exchange reactions were also investigated for different amines and diamines. The values of the standard molar enthalpy change for exchange reactions were obtained from temperature dependence of exchange constants (Kex) of complexes using the Van’t Hoff plots. The results show that the tendency of diamines to interaction with 18C6 is lower than the normal amines due to the intramolecular hydrogen bond formation. The Kex of diamines to interaction with 18C6 follows the order 1,2–diaminoethane (1,2–DAE)>1,3–diaminopropane (1,3–DAP)>1,5–diaminopentane (1,5–DAP)>1,4–diaminobutane (1,4–DAB). This trend indicates that the most stable intramolecular hydrogen bond is formed in 1, 4–DAB through the formation six-member cycles.

Toward ab initio potential energy surface for paclitaxel: a baccatin III conformational study

AbstractThe ab initio conformational energy profile of baccatin III, the diterpene part of paclitaxel, a natural, taxoid anticancer agent, has been investigated using medium‐size basis sets including an electron correlation method (MP2/DFT). By exploiting the internal coordinates using random search methods, 39 conformers of baccatin III were found. The most stable conformer, competing with its 13‐C rotamers, was shown to have three intramolecular hydrogen bonds of 1, 7 and 13 hydroxyls to the carbonyl oxygen atoms of 2‐benzoate and 10‐ and 4‐acetate ester groups, respectively. The results of the polarizable continuum model (PCM) used to account for the dielectric effect of the environment show that in water, the delicate balances between intramolecular hydrogen bridges and general conformational preferences are conserved, at least in the absence of explicit solvent molecules. Copyright © 2016 John Wiley & Sons, Ltd.

Coordination Properties of Perfluoroethyl- and Perfluorophenyl-Substituted Phosphonous acids, R(f)P(OH)2.

Phosphinic acids, R(f)P(O)(OH)H (R(f)=CF3, C2F5, C6F5), turned out to be excellent preligands for the coordination of phosphonous acids, R(f)P(OH)2. Addition of C2F5P(O)(OH)H to solid PtCl2 under different reaction conditions allows the isolation and full characterization of the mononuclear complexes [ClPt{P(C2F5)(OH)O}{P(C2F5)(OH)2}2] and [Pt{P(C2F5)(OH)O}2{P(C2F5)(OH)2}] containing hydrogen-bridged [R(f)P(OH)O](-) and R(f)P(OH)2 units. Further deprotonation of [Pt{P(C2F5)(OH)O}2{P(C2F5)(OH)2}2] leads to the formation of the dianionic platinate, [Pt{P(C2F5)(OH)O}4](2-), revealing four intramolecular hydrogen bridges. With PdCl2 the dinuclear complex [Pd2(μ-Cl)2{[P(C2F5)(OH)O]2H}2] was isolated and characterized. The Cl(-) free complex [Pd{P(C2F5)(OH)O}2{P(C2F5)(OH)2}2] was also prepared and deprotonated to the dianionic palladate, [Pd{P(C2F5)(OH)O}4](2-). Both compounds were characterized by NMR spectroscopy, IR spectroscopy, and X-ray analyses. In addition, the C6F5 derivatives [ClPt{P(C6F5)(OH)O}{P(C6F5)(OH)2}2] and [Pd2(μ-Cl)2{[P(C6F5)(OH)O]2H}2] as well as the CF3 derivative [Pd2(μ-Cl)2 {[P(CF3)(OH)O]2H}2] were synthesized and fully characterized. Phosphonous acid complexes are inert towards air and moisture and can be stored for several months without decomposition. The catalytic activity of the palladium complexes in the Suzuki cross-coupling reaction between 1-bromo-3-fluorobenzene and phenyl boronic acid was demonstrated.

Sterically Congested 5-Diphenylphosphinoacenaphth-6-yl-silanes and -silanols

The synthesis and characterization of the 5-diphenylphosphinoacenaphth-6-yl-silanes 5-Ph2P-Ace-6-SiMe2H (1), 5-Ph2P(S)-Ace-6-SiMe2H (1S), 5-Ph2P(Se)-Ace-6-SiMe2H (1Se), and 5-Ph2P-Ace-6-SiMe2Cl (2) as well as of the 5-diphenylphosphinoacenaphth-6-yl-silanols 5-Ph2P-Ace-6-SiMe2OH (3), 5-Ph2P(O)-Ace-6-SiMe2OH (3O), 5-Ph2P(S)-Ace-6-SiMe2OH (3S), and 5-Ph2P(Se)-Ace-6-SiMe2OH (3Se) are reported. Due to steric congestion in the bay area, the substituents in peri-positions are affected by repulsion, out-of-plane deflection, and distortion of the spatial arrangement to various extents. The peri-interaction energy associated with the steric congestion of these and a number of previously known reference compounds was computationally estimated with a set of isodesmic reactions. The organo-H-silanes 1, 1S, and 1Se possess very weak intramolecular hydrogen bridges of the types Si–H···P and Si–H···E═P (E = S, Se), whereas the organosilanols 3O, 3S, and 3Se contain medium-strength hydrogen bonds of the type Si–OH···E═P ...

Molecular Design of a Porphyrin Dimer with Features of P-Type and N-Type Heterojunctions by Chiral l-Glutamic Acid Induced Action

The structural features of chiral porphyrin dimers (CPDs) were studied by using UV–vis, 1H NMR, and XPS. These data illustrated that the intramolecular hydrogen bridge was formed, and the amidogen as the bridge of the intramolecular electron transfer promotes electron–hole separations in CPDs. The surface photovoltaic response of sandwich cells composed of CPDs was measured with the surface photovoltage spectrum (SPV) and electric-field-induced surface photovoltage spectroscopy (EFISPS). The surface photovoltaic signs show the CPD has features of not only the p-type but also n-type heterojunction.

The synthesis, characterization, and electrochemistry of molecular cobaloxime/organocobaloxime: catalysts for cycloaddition of carbon dioxide and epoxides

The new cobaloxime (1), organocobaloxime (2), and their intramolecular hydrogen (O–H⋯O) bridges replaced by Cu(II)-containing multinuclear cobaloximes (3–10) were synthesized and characterized by elemental analysis, 1H and 13C NMR spectra, FT-IR spectra, UV–vis spectra, LC-MS spectra, molar conductivity measurements, melting point measurements, and magnetic susceptibility measurements. Their electrochemical properties were investigated using cyclic voltammetric techniques in DMSO solution. The cobaloxime or organocobaloxime (1, 2) were used as precursors, replacing intramolecular O–H⋯O bridges, forming multinuclear complexes (3–10). Then, these compounds were used as homogeneous catalysts for cyclic carbonate synthesis from carbon dioxide (CO2) and epoxides. In the catalytic experiments, dimethyl amino pyridine (DMAP) was used as co-catalyst, since DMAP was a more active base with higher yield compared to other Lewis bases. It is not necessary to use solvent according to catalytic test results, important in green chemistry.

Synthese und Koordinationsverhalten neuer Schiffscher Basen aus 3-Formylacetylaceton und natürlichenL-Aminosäuren

Three novel chiral Schiff Base ligands (H2L) were prepared from the condensation reaction of 3-formyl acetylacetone with the amino acids L-alanine, L-phenylalanine, and L-threonine. X-ray single crystal analyses revealed that the Schiff Base compounds exist as enamine tautomers in the solid state. The molecular structure of the compounds is stabilized by an intramolecular hydrogen bridge between the enamine NH function and a carbonyl oxygen atom of the pentandione residue. Treatment of the ligands H2L with copper(II) actetate in the presence of pyridine led to the formation of copper complexes [CuL(py)]. In each of the complexes the copper atoms adopt a distorted square-pyramidal coordination. Three of the basal coordination sites are occupied by the doubly deprotonated Schiff Bases L2– which act as tridentate chelating O, N, O-ligands. The remaining coordination sites are occupied by a pyridine ligand at the base and a carboxyl oxygen atom of a neighboring complex at the apical position. The latter coordination is responsible for a catenation of the complexes in the solid state.

The multinuclear cobaloxime complexes-based catalysts for direct synthesis of cyclic carbonate from of epichlorohydrin using carbon dioxide: Synthesis and characterization

The novel examples of dicobaloxime [(dmgH)2ClCo-(4,4′-bpy)-CoCl(dmgH)2] (1), organodicobaloxime [(dmgH)2PhCH2Co-(4,4′-bpy)-CoCH2Ph(dmgH)2] (2), and the intramolecular hydrogen (O–H⋯O) bridges were replaced Cu(II) containing multinuclear cobaloxime complexes [{dmgCu(NN)}2ClCo-(4,4′-bpy)-CoCl{dmgCu(N—N)}2](ClO4)4 (3–9) were synthesized, characterized and used in direct synthesis cyclic carbonates from carbon dioxide and various epoxides. The dicobaloxime complex (1) was used as precursors for building the intramolecular hydrogen (O–H⋯O) bridges replaced Cu(II) ions containing complexes (3–9). All of compounds have been characterized by 1H and 13C NMR spectra, FT-IR spectra, UV–Vis spectra, elemental analysis, melting point measurements, LC-MS spectra, molar conductivity measurements, and magnetic susceptibility techniques. Among the nine metal complexes, complex (2) (bearing cobalt–carbon bound) displayed the higher catalytic efficient than other complexes (1 and 3–9) under the same catalytic conditions. The intramolecular hydrogen (O–H⋯O) bridges were replaced Cu(II) containing complexes (3–9) that bear the dimethyl glyoximate ligands and linked ligands exhibited much lower catalytic efficiencies as compared with complexes (1) and (2).

Theoretical and spectroscopic studies on molecular structure and hydrogen bonding of 1,2-bis (monochloroacetyl) cyclopentadiene

1,2-Bis (monochloroacetyl) cyclopentadiene (MCACP) was synthesized and its molecular structure, intramolecular hydrogen bonding, and vibrational frequencies were investigated by means of density functional theory (DFT) calculations, NMR, and IR spectroscopies. It was found that the most stable conformers are those stabilized by intramolecular hydrogen bridges. Calculations at the B3LYP level, using 6-31G(d,p), 6-311G(d,p), and 6-311++G(d,p) basis sets, have been carried out for understanding the strength of hydrogen bond. In addition, the energies of the stable chelated conformers and their corresponding open structures were obtained at the MP2/6-31G(d,p) level of theory. The harmonic vibrational wavenumbers of MCACP and its deuterated analogue were obtained at the B3LYP/6-311++G(d,p) level. 1H and 13CNMR spectra were recorded and 1H and 13C nuclear magnetic resonance chemical shifts of the molecule were calculated using the gauge independent atomic orbital (GIAO) method. The calculated geometrical parameters and relative energies show formation of a very strong intramolecular hydrogen bond that is consistent with the frequency shifts for OH/OD stretching, OH/OD out-of-plane bending, and O⋯O stretching modes and proton chemical shift. The rotation of terminal CH2Cl groups indicates existence of two stable conformers that their hydrogen bond energy was estimated to be, on average, about 75.6kJ/mol. The nucleus-independent chemical shift (NICS) data in the keto and enol forms indicated that in addition to differences in stability due to hydrogen bonding, differing stability also arises from the aromaticity increase of cyclopentadene (CP) ring in the chelated forms.

Nitrogen and carbon CPMAS NMR investigations of keto–enol tautomerism in asymmetric o-hydroxy Schiff bases

The five Schiff bases obtained by condensation of dehydroacetic acid, p-phenylenediamine and derivatives of salicylaldehyde were investigated by 13C and 15N CPMAS NMR methods to find the structure of intramolecular hydrogen bridges. Additionally the 15N NMR spectra in CDCl3 were done. The results obtained in the solid state and in solution were compared with the X-ray previously published for some of investigated compounds. The relatively small influence of substituent in salicylaldehyde unit on proton position was found as well as only small difference in the hydrogen bridges structure in both phases, solution and solid state, which is in contrast with results acquired for Schiff bases obtained from simple aliphatic amines.

Formation of Melamium Adducts by Pyrolysis of Thiourea or Melamine/NH4Cl Mixtures

Pyrolysis of prominent precursor compounds for the synthesis of carbon nitride type materials (e.g., melamine, thiourea) have been studied in detail. Molecular adducts containing monoprotonated melamium C(6)N(11)H(10)(+) and melaminium HC(3)N(3)(NH(2))(3)(+) ions, respectively, have been identified as intermediates. The adduct C(6)N(11)H(10)Cl·0.5NH(4)Cl was obtained by the reaction of melamine C(3)N(3)(NH(2))(3) with NH(4)Cl at 450 °C. During the pyrolysis of thiourea, guanidinium thiocyanate was initially formed and subsequently the melamium thiocyanate melamine adduct C(6)N(11)H(10)SCN·2C(3)N(3)(NH(2))(3) was isolated at 300 °C. A second melaminium thiocyanate melamine adduct with the formula HC(3)N(3)(NH(2))(3)SCN·2C(3)N(3)(NH(2))(3) represents an intermediary reaction product that is best accessible at low pressures. The crystal structures of the compounds were solved by single-crystal XRD. Unequivocal proton localization at the C(6)N(11)H(10)(+) ion was established. A typical intramolecular and interannular hydrogen bridge and other characteristic hydrogen-bonding motifs were identified. Additionally, the adducts were investigated by solid-state NMR spectroscopy. Our study provides detailed insight into the thermal condensation of thiourea by identifying and characterizing key intermediates involved in the condensation process leading to carbon nitride type materials. Furthermore, factors promoting the formation of melamium adduct phases over melem are discussed.

Indigo stability: an ab initio study

This work shows that indigo's high stability can be attributed both to the large π conjugation inside the molecule and to intra- and intermolecular hydrogen bonds. The theoretical investigation of indigo's electronic structure has been performed using high-level methods. To understand the interactions in solid state, calculations of the dimer system with both molecules in the same plane was carried out. In the monomer, two intramolecular hydrogen bridges between amino and carbonyl groups occupy positions that would otherwise be the most reactive ones for nucleophilic and electrophilic attacks. In the dimer, amino and carbonyl groups on different monomers form intermolecular multicentred non-linear hydrogen bonds in six-member rings, protecting again the same reactive centres and explaining the limited solubility of indigo. The addition of the free radical OH breaks the central C = C double bond, the conjugation and the hydrogen bridges as a first step. The Gibbs energy calculation favours the addition of OH radical over C1.

Hydrogen Peroxide Elimination from C4a-hydroperoxyflavin in a Flavoprotein Oxidase Occurs through a Single Proton Transfer from Flavin N5 to a Peroxide Leaving Group

C4a-hydroperoxyflavin is found commonly in the reactions of flavin-dependent monooxygenases, in which it plays a key role as an intermediate that incorporates an oxygen atom into substrates. Only recently has evidence for its involvement in the reactions of flavoprotein oxidases been reported. Previous studies of pyranose 2-oxidase (P2O), an enzyme catalyzing the oxidation of pyranoses using oxygen as an electron acceptor to generate oxidized sugars and hydrogen peroxide (H(2)O(2)), have shown that C4a-hydroperoxyflavin forms in P2O reactions before it eliminates H(2)O(2) as a product (Sucharitakul, J., Prongjit, M., Haltrich, D., and Chaiyen, P. (2008) Biochemistry 47, 8485-8490). In this report, the solvent kinetic isotope effects (SKIE) on the reaction of reduced P2O with oxygen were investigated using transient kinetics. Our results showed that D(2)O has a negligible effect on the formation of C4a-hydroperoxyflavin. The ensuing step of H(2)O(2) elimination from C4a-hydroperoxyflavin was shown to be modulated by an SKIE of 2.8 ± 0.2, and a proton inventory analysis of this step indicates a linear plot. These data suggest that a single-proton transfer process causes SKIE at the H(2)O(2) elimination step. Double and single mixing stopped-flow experiments performed in H(2)O buffer revealed that reduced flavin specifically labeled with deuterium at the flavin N5 position generated kinetic isotope effects similar to those found with experiments performed with the enzyme pre-equilibrated in D(2)O buffer. This suggests that the proton at the flavin N5 position is responsible for the SKIE and is the proton-in-flight that is transferred during the transition state. The mechanism of H(2)O(2) elimination from C4a-hydroperoxyflavin is consistent with a single proton transfer from the flavin N5 to the peroxide leaving group, possibly via the formation of an intramolecular hydrogen bridge.

Deprotonation of hydrogen bonded Schiff bases by three strong nitrogen bases

Three Schiff bases obtained from substituted salicylaldehydes and 2-hydroxy-1-naphthaldehyde and aliphatic amines were investigated in terms of possible withdrawal of tautomeric proton from intramolecular hydrogen bridge. Three strong nitrogen bases: 1,8-bis(dimethylamino)naphtalene (DMAN), 1,1,3,3-tetramethylguanidine (TMG) and 1,8-bis(tetramethylguanidino)naphthalene (TMGN) were used as deprotonating agents in acetonitrile solution at room temperature. In the specified conditions it was found that only in the case of 5-nitrosalicylaldehyde and isopropyl amine derivative this process could be performed using TMG and TMGN as a base. The other derivatives, where bridged proton is shifted to oxygen or nitrogen atom, do not undergo such reaction. The deprotonation process was monitored by nitrogen and proton NMR measurements.