Bridging Proton Research Articles

Enthalpic Studies of Complex Formation between Carboxylic Acids and 1-Alkylimidazoles

The nature of the hydrogen bonding in complexes of alkylimidazoles and substituted carboxylic acids has been studied as a model of the hydrogen-bonding interaction of the proton bridging Nδ1 of His 57 and the β carboxyl group of Asp 102 in the active site of chymotrypsin. The interaction has been postulated to be a low barrier hydrogen bond (LBHB) in the enzyme and also in the model complexes which have a small ΔpKa. In the present study, enthalpies of complex formation, −ΔHformation, between alkylimidazoles (1-methyl, 1-n-butyl-, and 1-tert-butylimidazole) and a series of carboxylic acids were determined by adiabatic solution calorimetry in chloroform. In FTIR studies presented here, the concentration of LBHB present in these complexes was determined. For complexation between dichloropropionic acid and alkylimidazoles for which the ΔpKa is small in chloroform, the −ΔHformation values varied from 12 to 15 kcal/mol. Thus in enzymes, where ΔG is similar to ΔH, ΔGformation can be as high as −12 to −15 kcal/mol for LBHBs. If a weak hydrogen bond in the initial E·substrate complex with a ΔGformation of ≤−5 kcal/mol is converted to a low barrier hydrogen bond in the transition state, there will be 7−10 kcal/mol of energy available to lower the activation barrier and accelerate the reaction by 5−7 orders of magnitude.

Structures of arachno- and hypho-B(10) Clusters and Stability of Their Possible Lewis Base Adducts ([B(10)H(12)](2-), [B(10)H(12).L](2)(-), [B(10)H(12).2L](2)(-), [B(10)H(13)](-), [B(10)H(13).L](-), [B(10)H(12).2L]). An ab Initio/IGLO/NMR Investigation.

The [B(10)H(12)](2)(-) dianion has been shown by the ab initio/IGLO/NMR method to have a C(2) symmetric structure (26) derived from B(10)H(14) (17) by removing two opposite bridge protons. Adduct formation with one or two solvent molecules, suggested on the basis of experimental NMR investigations, does not take place. [B(10)H(12).nL](2)(-) (n = 1, 2) structures with various ligands are not bound (vs [B(10)H(12)](2)(-) and n L) and do not reproduce the experimental (11)B NMR chemical shifts. The [B(10)H(13)](-) structure (19), computed to have C(1) rather than C(s)() symmetry in solution (as in the solid state), also can be derived from B(10)H(14) (17) by removal of a bridging proton. In both the mono- (19) and the dianion (26), a bridging hydrogen can rearrange easily from B5/B6 to B9/B10 (barrier ca. 5 kcal mol(-)(1)) but not from B8/B9 to B9/B10 (barrier ca. 15 kcal mol(-)(1)). The recently proposed 6,6-(C(5)H(5)N)(2)B(10)H(12) structure is not supported computationally.

Experimental Observation of Excited-State Electron Transfer Quenching Involving Exchange-Coupled Dinuclear Fe(III) Complexes.

Bimolecular electron transfer quenching of the 3MLCT excited state of [Ru(dmb)3]2+ by dinuclear complexes of FeIII has been observed. Compounds of the general form [Fe2(μ-O(H))(μ-O2CCH3)2(Tp)2]n+ (Tp = hydrotris(1-pyrazolyl)borate) react following photoexcitation of [Ru(dmb)3]2+ with bimolecular quenching rate constants of kq = (7.1 ± 0.3) × 108 M-1 s-1 for Fe2O(O2CCH3)2(Tp)2 and (5.15 ± 0.15) × 109 M-1 s-1 for [Fe2(OH)(O2CCH3)2(Tp)2]+. It is suggested that the inferred difference in electron transfer rates may be related to the change in intramolecular Heisenberg exchange that accompanies protonation of the oxo bridge.

The [NHN] − homoconjugated anions: X-ray diffraction, IR and multinuclear MR studies

X-ray diffraction, IR and NMR studies are reported on chemically symmetric [NHN] − anions formed by 1,8-bis(4-toluenesulphonamido)naphthalene, 1,8-bis(trifluoroacetamido)naphthalene, 1,8-diamino-2,4,5,7-tetranitronaphthalene and di-4-nitroimidazolyl-5-sulphide after abstraction of a proton by means of the proton sponge (DMAN), and in the 2:1 adducts of 4,5-dicyanoimidazole and 2-amino-4,5-dicyanoimidazole with DMAN as well as in the conjugated tetrazole-tetrazolate anion. The anionic NHN − hydrogen bonds studied so far are markedly weaker as compared with NHN + cationic ones of similar geometry. They are characterized by an asymmetric, in the scale of vibrations, H-atom localization in the bridge with the protonic (NHN) − band located usually in the region 2600–3000 cm −1. The δ 1H value in acetonitrile of the bridge proton in [NHN] − anions studied until now is between 14.1 and 16.4 ppm, while that in protonated DMAN is 18.7 ppm. The studies on 15N chemical shift and 15N 1H coupling constant yielded additional information on the symmetry of [NHN] − bridges and localization of the bridge H-atom.

Highly diastereoselective formation of stable fulleroids

The highly regio- and diastereoselective formation of the cluster opened fulleroid isomers 12 via thermal decomposition of the corresponding pyrazolines 11 is reported. In the diastereomers 12 the protons of the monoalkylated methylene bridge are located above a six-membered ring and the bulkier alkyl groups above a five-membered ring. The corresponding methanofullerenes were not detected and the diastereomeric fulleroids 13 with the methylene bridge proton above a five-membered ring are formed only in traces. The pyrazoline 11a is the first example of a substituted pyrazolino[60]fullerene. The present experimental and computational investigations provide important information on the mechanism of this most fundamental cluster opening process in fullerene chemistry.

The contributions of secondary proton bridges to the catalytic power of the serine proteases

AbstractThe curvature of proton‐inventory functions (rate constants in mixtures of protium and deuterium oxides) for hydrolysis of substrates of varying structure by trypsins from four different sources has been used as a signal of transition‐state stabilization by a short, strong hydrogen bonds (“low‐barrier hydrogen bonds”) at the histidine‐aspartate site of the catalytic triad. Previous estimates suggested contributions as large as 85 kJ mol−1 but the current findings are consistent with contributions of no more than a few kJ mol−1.

The crystal stucture of the nitric acid adducts of triphenylarsine oxide and triphenylphosphine oxide

Molecular dimensions suggest that three crystal forms of the nitric acid adduct of triphenylarsine oxide have the bridging proton more closely associated with the As=O group than with the nitrate moiety, whereas the corresponding phosphorus compound has the proton more closely associated with the nitrate moiety. In all cases, strong hydrogen bonds are formed between the two moieties resulting in XO bonds (where X=As or P) intermediate in character between single and double bonds.

X-ray and NMR investigation of 25,27-dihydroxy-26,28-bis(diethoxyphosphoryloxy)-tert-butylcalix[4]arene in the1,2-alternate conformation

The crystal structure of 25,27-dihydroxy-26,28-bis(diethoxyphosphoryloxy)-tert-butylcalix[4]arene (1) (hexane solvate, 1:1) was determined by x-ray crystallography. The crystal data are P21/n, a = 12.652(1) Å, b = 12.564(2) Å, c = 18.781(4) Å, β = 105.56(1)°, V = 2876.0(8) Å3, Z = 2. In this complex the molecule adopts a 1,2-alternate conformation. Both the calixarene and hexane molecules are centrosymmetric. The phenol units in the asymmetric part of the calix are inclined with respect to the main macrocyclic plane by 115.46(6)° and 128.01(7)° for the phosphorylated and the non-phosphorylated ring, respectively. Self-inclusion of the ethyl chains in the half-cavities is observed. One intramolecular O—H…O and several intermolecular C—H…O hydrogen bonds are present. In the 1H NMR spectrum one average AX spin system for methylene bridge protons can be interpreted as fast (on the NMR time-scale) interconversion of non-phosphorylated phenol fragments. © 1998 John Wiley & Sons, Ltd.

Stereospecific interactions of chiral cobalt(III)-amine complexes with guanosine 5′-monophosphate

The interactions of two chiral cobalt(III)-amine complex cations, [Co(sep)] 3+ where sep = sepulchrate (1, 3, 6, 8,10,13,16,19-octaazabicyclo[6.6.6]eicosane), and [Co(tetren)(OH)] 2+ where tetren = tetraethylene-pentaamine (1,4,7,10,13-pentaazatridecane), with guanosine 5′-monophospbate (5′-GMP) were characterized in the solid state and in aqueous solution. 1H nuclear magnetic resonance (AMR,) studies show that interactions persist even in dilute solutions of this compound. The 1H NMR spectrum of the products formed when racemic [Co(sep)] 3+ reacts with β- d-5′-GMP reveals a splitting o the AB multiplet of the methylene bridge protons of [CO(sep)] 3+ into two AB multiplets of equal intensity. This is shown to be the result of the formation of the diastereomers [Λ-(+)-Co(sep)] 2(β- d-GMP) 3 and [δ-(−)-Co(sep)] 2(β- d-5′-GMP) 3. The phosphate is not involved in covalent bonding, but could be participating in hydrogen bonding. Fourier transform infrared data of solid [Co(sep)] 2(5′-GMP) 3 · 12H 20 suggest the possibility of hydrogen bonding of N-H sites on the cobalt ligands with N7 and 06 of the guanine base. The compound {[Co(tetren)] 2(5′-GMP)}(ClO 4) 4 · 6H 20 was synthesized and it was found that the phosphate was covalently bonded to the Co(III). The solid decomposes into [Co(tetren) (5′-GMP)] + in aqueous solution. Di-astereomer formation is observed in the 31P NMR when [Co(tetren)(5′-GMP)] + is formed in solution from racemic [Co(tetren)(OH)] 2+ and β- d-5′-GMP 2−, and 1H NMR reveals interactions between the etbylenic protons and guanine moiety. The K′ assoc for [Co(tetren (5′-GMP)] + is 0.17 ± 0.05. Molecular modeling was done and the structures determined correlated well with the experimental data. These Co(III)-amine complex ions illustrate the variety of highly specific interactions which can occur with biomolecules.

Strong hydrogen bonding in the gas phase: fluoromethane⋯hydronium versus fluoromethane⋯ammonium

The proton-bound heterodimers MeF⋯HOH 2 + and MeF⋯HNH 3 + are here reported for the first time. Ion structures have been characterized by collisionally-induced dissociation and their enthalpies of association computed ab initio at the MP4(SDQ)/6–311G ∗∗ 6D level as ΔH 450° = - 105.9 kJ mol −1 and ΔH 450° = − 71.0 ± 0.8 kJ mol −1, respectively. Complete equilibration between the latter species and its constituents has been demonstrated at a pressure of 0.48 Torr in the ion source: establishment of equilibrium at that pressure takes place on the 0.1 ms timescale at 190°C. Theoretical van't Hoff plots give ab initio entropies of association, which match the experimental value published for H 2O⋯HNH 3 +. The value for McF⋯HOH 2 + is ΔS 450° = − 103.0 J mol −1 K −1, but the entropy for MeF⋯HNH 3 + depends on how the ammonium rocking motions are considered in the large-amplitude limit. Viewing them as a pair of harmonic vibrations yields ΔS 450° = − 68.1 J mol −1 K −1, while looking at these degrees of freedom as a two-dimensional hindered internal rotor gives ΔS 450° = − 17.6 ± 1.1 or ΔS 450° = − 52.3 ± 1.1 J mol −1 K −1, depending on whether internal rotation is treated as completely coupled or completely uncoupled from external rotation. Analysis of calculated vibrational frequencies, electron densities, and rotational barriers leads to the conclusion that the large difference in entropy of association between MeF⋯HOH 2 + and MeF⋯HNH 3 + reflects the low degree of covalency in the ammonium-fluorine proton bridge and the comparative accessibility of purely electrostatic bonding orientations.

NHN]+ and [OHO]− hydrogen bonding in the adduct of 1,8-bis(dimethylamino)naphthalene (DMAN) with 1,8-dihydroxy-2,4-dinitronaphthalene (DHDNN)

X-Ray diffraction, IR and 1H NMR studies were performed on the 1:1 adduct of 1,8-bis(dimethylamino)naphthalene (DMAN) with 1,8-dihydroxy-2,4-dinitronaphthalene (DHDNN). The adduct crystallizes in the triclinic system, space group Pl̄, a = 9.911(2) Å, b = 11.212(2) Å, c = 11.194(2) Å, α = 68.95(2)°, β = 79.72(2)°, γ = 73.78(2)°, Z = 2. Both [NHN]+ and [OHO]− hydrogen bonds formed in the ion pairs are asymmetrical with lengths equal to 2.574(2) Å and 2.466(4) Å respectively. The [NHN]+ bridge shows a typical behaviour in the IR spectrum, i.e. a low-frequency absorption between 300 and 700 cm−1. The coupling of [OHO]− hydrogen bonds with the naphthalene π-electron system is so strong that no absorption related to the proton stretching vibrations can be detected in the high- and low-frequency regions. The 1H NMR chemical shifts for the [NHN]+ and [OHO]− bridge protons of 18.63 and 15.81 ppm respectively confirm the strong hydrogen bonds.

A 1H, 13C and 15N NMR study of 4-nitro-bis(dimenthylamino)naphthalene and its protonated form

1H, 13C and 15N data are reported for 4-nitro-bis(dimenthylamino)naphthalene (DMAN) 1 and its protonated form 2. The results obtained reveal the presence of an unsymmetrical [N–H–N] + structure for 2. Both the nitrogen shielding data and the observation of two values of 1J( 15N– 1H) and 3J( 1H– 1H) in the approximate ratio of 1:2 show that the bridging proton has a greater preference for N(8) than for N(1). © 1997 Elsevier Science B.V.

EPR study of the mixed-valent diiron sites in mouse and herpes simplex virus ribonucleotide reductases. Effect of the tyrosyl radical on structure and reactivity of the diferric center.

Reduction of ribonucleotide reductase (EC 1.17.4.1) R2 proteins in a frozen glycerol-buffer solution at 77 K by mobile electrons generated by gamma-irradiation produces EPR-detectable iron sites in mixed-valent Fe(II)/Fe(III) states. The primary EPR signals give information about the ligand arrangement of the diferric form of the iron site, whereas secondary signals observed after annealing of the sample show the effects of structural relaxation. In recombinant metR2 proteins (without free radical) from mouse and herpes virus type 1, the mixed-valent sites trapped at 77 K give rise to axial S = 1/2 EPR spectra with g values in the range 1.79-1.94, observable at temperatures up to 110 K. The spectra are assigned to mu-oxo-bridged dinuclear iron sites. In mouse metR2, the primary EPR spectrum is a mixture of two components. Annealing the R2 samples to 160-170 K transforms the primary EPR signals into rhombic spectra, characterized by gav < 1.8, and observable only below 25 K. These spectra are assigned to partially relaxed forms with a mu-hydroxo bridge, formed by protonation of the oxo bridge. Further annealing at 220 K produces new rhombic EPR spectra, which are closely similar with those observed and found to be stable after chemical reduction at room temperature. The EPR signal of the primary mixed-valent iron site in active mouse R2 protein with a tyrosyl radical also has two components. Both are different from those observed in metR2. In herpes simplex virus type 1 protein R2, one primary mixed-valent component was observed for the met protein. The dose-yield curve for the mixed-valent state in active mouse R2 is sigmoidal in shape, indicating that the tyrosyl radical is reduced by mobile electrons before the iron site. Kinetic experiments on the reduction by dithionite on mouse R2 without and with radical show a significantly enhanced rate for reduction of the iron site in the protein without radical. The results suggest that in active mouse R2 only complete diferric sites with neighboring radicals give rise to the mixed-valent spectra, and that these sites may exist in two structurally distinct forms. The results on the mouse R2 proteins confirm and extend previous results obtained on the Escherichia coli protein R2 showing that the presence of the tyrosyl radical significantly affects not only the structure but also the reactivity of the iron site.

Azide adducts of stearoyl-ACP desaturase: a model for μ-1,2 bridging by dioxygen in the binuclear iron active site

The stearoyl-acyl carrier protein Δ9 desaturase (Δ9D) uses an oxo-bridged diiron center to catalyze the NAD(P)H– and O2–dependent desaturation of stearoyl-ACP. Δ9D, ribonucleotide reductase, and methane monooxygenase have substantial similarities in their amino acid primary sequences and the physical properties of their diiron centers. These three enzymes also appear to share common features of their reaction cycles, including the binding of O2 to the diferrous state and the subsequent generation of transient diferric-peroxo and diferryl species. In order to investigate the coordination environment of the proposed diferric-peroxo intermediate, we have studied the binding of azide to the diiron center of Δ9D using optical, resonance Raman (RR), and transient kinetic spectroscopic methods. The addition of azide results in the appearance of new absorption bands at 325 nm and 440 nm (kapp≈3.5 s–1 in 0.7 M NaN3, pH 7.8). RR experiments demonstrate the existence of two different adducts: an η1–terminal structure at pH 7.8 (14N3– asymmetric stretch at 2073 cm–1, resolved into two bands with 15N14N2–) and a μ-1,3 bridging structure at pH<7 (14N3– asymmetric stretch at 2100 cm–1, shifted as a single band with 15N14N2–). Both adducts also exhibit an Fe–N3 stretching mode at ≈380 cm–1, but no accompanying Fe–O–Fe stretching mode, presumably due to either protonation or loss of the oxo bridge. The ability to form a μ-1,3 bridging azide supports the likelihood of a μ-1,2 bridging peroxide as a catalytic intermediate in the Δ9D reaction cycle and underscores the adaptability of binuclear sites to different bridging geometries.

Reversible on/off switching of [formula omitted] interactions in rhodathiaboranes with “anomalous” electron counts. Synthesis and molecular structure of [(Ph 3P 2N][1-dppe-1,2- closo-RhSB 9H 9

Reconsideration of the “rule-breaking” rhodathiaborane 8,8-(Ph 3P) 2-8,7- nido-RhSB 9H 10, its 9-OEt and dppe analogues, reveals the existence of agostic CH ⇀ Rh (from PPh 3) bonding which accounts for its molecular structure. Deprotonation [H(9, 10) bridging proton] “switches off” this agostic bonding and affords a closo cluster. This structural change is fully reversible on reprotonation.

Is cysteine residue important in FITC-sensitive ATP-binding site of P-type ATPases? A commentary to the state of the art.

Treatment of P-type ATPases (from mammalian sources) by fluorescein isothiocyanate (ITC) revealed the ITC label on a lysine residue that was than considered as essential for binding of ATP in the ATP-binding site of these enzymes. On the other hand, experiments with site directed mutagenesis excluded the presence of an essential Iysine residue that would be localized in the ATP binding sites of ATPases. Other previous studies, including those of ourselves, indicated that the primary site of isothiocyanate interaction may be the sulfhydryl group of a cysteine residue and this may be essential for binding of ATP. In addition considerable knowledge accumulated since yet also about the differences in stability of reaction product of isothiocyanates with SH- or NH2- groups. Based upon evaluation of the data available up to now, in present paper the following tentative roles for lysine and cysteine residues located in the ATP-binding site of P-type ATPases are proposed: The positively charged micro-domain of the lysine residue may probably attract the negatively charged phosphate moiety of the ATP molecule whereas the cysteine residue may probably be responsible for recognition and binding of ATP by creation of a proton bridge with the amino group in position 6 on the adenosine ring of ATP.

Synthesis, NMR and ultraviolet spectroscopy of [10] (N6,9)-6-aminopurinophane; calculation of the chemical shifts in the [n](N6,9)-6-aminopurinophane series

[10](N6,9)-6-Aminopurinophane was prepared via a Mitsunobu reaction involving 6-chloropurine and 10-azido-1-decanol. Reduction of the azido moiety to an amine allowed for subsequent cyclization to the cyclophane. N6-Nonyladenine, 9-nonyladenine, and N6,9-dinonyladenine were also prepared using the established chemistry. Heating the [10](N6,9)-6-aminopurinophane to 90 °C allowed for a complete assignment of the proton and carbon spectra, while cooling the sample to −77 °C revealed additional isomers likely due to the anti–syn isomerization about the N6—C6 bond. A variable temperature proton NMR study revealed a ΔGc≠ of 59.4 ± 5.5 kJ mol−1 associated with the interchange between the two major conformers. The ultraviolet spectra of the [n](N6,9)-6-aminopurinophane series show a bathochromic shift and a hypochromic effect in the transitions as the methylene chain length decreases (i.e., n = 10 to 9 to 8). The aminopurinophanes are used to assess the relative merits of a semi-empirical model that allows for the calculation of the chemical shifts of the methylene bridge protons. Keywords: synthesis of heterocyclophanes, variable temperature NMR, cyclophane conformational analysis, ultraviolet spectroscopy, calculation of chemical shift.

The role of the CC double bond in alcohol elimination from MH+ ions of unsaturated bicyclic esters upon chemical ionization

AbstractMethyl and ethyl endo‐ and exo‐bicyclo [2.2.2] oct‐5‐ene‐2‐carboxylates exhibit different mass spectral behaviour under i‐Bu‐chemical ionization (CI) conditions and upon collision‐induced dissociation (CID) of their MH+ IONS. The endo‐esters exhibit m/z 135 [MH  MeOH]+ and [MH  EtOH]+ ions, which are absent in the i‐Bu‐CI mass spectra of the exo‐isomers. This stereospecific behavior is explained in terms of the proton bridging requirement in the alcohol elimination from MH+ ions of esters. Such proton bridging between the alkoxycarbonyl group and the double bond is possible in the endo‐esters, but not in the exo‐isomers. Hydrogen‐deuterium exchange processes, observed in the CID spectra of the MD+ ion of the endo‐esters, support the proposed mechanistic pathway. Hydrogen bridging with the double bond also plays a role in the alcohol elimination processes of stereoisomeric bicyclo [2.2.2] oct‐5‐ene‐2,3‐dicarboxylates.

Comparison of gas‐phase basicities and ion–molecule reactions of aminobenzoic acids

AbstractFunctional group interactions and substituent effects of o‐, m‐ and p‐aminobenzoic acids were examined in a quadrupole ion trap by evaluation of proton‐transfer and methylene substitution reactions. An electron‐withdrawing carboxylic acid group can enhance or reduce the gas‐phase basicity of aniline depending on its location and ability to participate directly in proton bridging. In fact, the gas‐phase basicity of o‐aminobenzoic acid is enhanced by ∼ 7 kcal mol−1 relative to the meta and para isomers in which the substituents do not have cooperative functional group interactions. Collisionally activated dissociation studies of deuterium‐labeled ions provide evidence of proton migration from the amino group to the carboxylic acid group prior to fragmentation. Results of semi‐empirical molecular orbital calculations provided structures for the various protonated aminobenzoic acids. For o‐aminobenzoic acid, the proton bridges between the acid and amine groups.

1H and 13C NMR and FT-IR studies of the interaction between 1,8-bis(dimethylamino)naphthalene and 3,5-dichlorophenol

The 1H and 13C NMR spectra of the complex between 1,8-bis(dimethylamino)naphthalene and 3,5-dichlorophenol have been studied at temperatures between 30 °C and –70 °C in CD2Cl2 and at different acid to base concentration ratios. At a temperature of –60 °C a splitting of the 1H and 13C signals of DMAN and DMANH+ is observed. The protonation degree deduced from the NMR data and the intensity of the Bohlmann bands are in very good agreement. At a temperature below 8 °C, a splitting (2.6 Hz) of the methyl protons caused by spin–spin coupling with the (NHN)+ bridge protons is observed. Comparison with literature data and with the coupling constant determined in this work for protonated N,N-dimethylaniline suggest that the potential surface of the NHN+ cation includes two symmetrically situated wells between which fast proton migration takes place.