N-protonated Form Research Articles

PH-Dependent molecular switch based on Pv porphyrin

Water-soluble phosphorus(v) porphyrin with p-amino- phenoxy groups as axial ligands was obtained, and its photophysical and photochemical properties were investigated and rationalized using quantum chemical calculations. It was demonstrated that at pH ≥ 6.1 this porphyrin did not emit or generate singlet oxygen, whereas at pH ≤ 2.0 it completely converted into the N-protonated form, which exhibited fluorescence and the ability to generate singlet oxygen.

Unidirectional Double- and Triple-Hydrogen Rearrangement Reactions Probed by Infrared Ion Spectroscopy.

Unidirectional double-hydrogen (2H) and triple-hydrogen (3H) rearrangement reactions occur upon electron-ionization-induced fragmentation of trans-2-(4-N,N-dimethylaminobenzyl)-1-indanol (1), trans-2-(4-methoxybenzyl)-1-indanol (2), 4-(4-N,N-dimethylaminophenyl)-2-butanol (3), and related compounds, as reported some 35 years ago (Kuck, D.; Filges, U. Org. Mass Spectrom. 1988, 23, 643-653). These unusual intramolecular redox processes were found to dominate the mass spectra of long-lived, metastable ions. The present report provides independent evidence for the structures of the product ions formed by the 2H and 3H rearrangement in an ion trap instrument. The radical cations 1•+ and 3•+ as well as ionized 1-(4-N,N-dimethylaminophenyl)-5-(4-methoxyphenyl)-3-pentanol, 5•+, were generated by electrospray ionization from anhydrous acetonitrile solutions. The 2H and 3H fragment ions were obtained by collision-induced dissociation and characterized by IR ion spectroscopy and density functional theory calculations. Comparison of the experimental and calculated infrared ion spectra enabled the identification of the 2H rearrangement product ion, C9H14N+ (m/z 136), as an N,N-dimethyl-para-toluidinium ion bearing the extra proton ortho to the amino group, a tautomer which was calculated to be 31 kJ/mol less stable than the corresponding N-protonated form. The 3H rearrangement product ion, C8H13N•+ (m/z 123), formerly assumed to be a distonic ammonium ion bearing a cyclohexadienyl radical, was now identified as a conventional radical cation, ionized N,N-dimethyl-2,3-dihydro-para-toluidine. Thus, the 3H rearrangement represents an intramolecular transfer hydrogenation between a secondary alcohol and an ionized aromatic ring. Based on these structural assignments, more detailed mechanisms for the unidirectional 2H and 3H rearrangement reactions are proposed.

Effects of Aromatic Stabilization Energies on Photochromism of New Asymmetrical Azaindole‐Containing Diarylethenes

AbstractThree new asymmetrical diarylethenes containing an azaindole moiety and a variable heteroaryl ring have been synthesized. Their properties, such as photochromism, fatigue resistance, thermal stability, acidichromism, and fluorescence, were systematically investigated to elucidate the effects of aromatic stabilization energies (ASE) of the heteroaryl moieties. The results indicated that thermal stability decreased with the increment of the aromatic stabilization energies of the variable heteroaryl rings in the order of thiazyl<thienyl<pyrrolyl. Moreover, the dual switching behaviors of these azaindole‐containing diarylethenes were also studied by the stimulation of acid/base and light. Addition of trifluoroacetic acid to the solutions of these diarylethenes resulted in obvious hypochromic shifts, and their N‐protonated forms also exhibited favorable photochromism.

Protomers of benzocaine: solvent and permittivity dependence.

The immediate environment of a molecule can have a profound influence on its properties. Benzocaine, the ethyl ester of para-aminobenzoic acid that finds an application as a local anesthetic, is found to adopt in its protonated form at least two populations of distinct structures in the gas phase, and their relative intensities strongly depend on the properties of the solvent used in the electrospray ionization process. Here, we combine IR-vibrational spectroscopy with ion mobility-mass spectrometry to yield gas-phase IR spectra of simultaneously m/z and drift-time-resolved species of benzocaine. The results allow for an unambiguous identification of two protomeric species: the N- and O-protonated forms. Density functional theory calculations link these structures to the most stable solution and gas-phase structures, respectively, with the electric properties of the surrounding medium being the main determinant for the preferred protonation site. The fact that the N-protonated form of benzocaine can be found in the gas phase is owed to kinetic trapping of the solution-phase structure during transfer into the experimental setup. These observations confirm earlier studies on similar molecules where N- and O-protonation have been suggested.

Mechanistic insights into the catalysis of electrochemical proton reduction by a diiron azadithiolate complex.

Cyclic voltammetry experiments and DFT calculations allowed us to establish a complete mechanism of the catalysis of electrochemical proton reduction by [Fe2(μ-SCH2N(H)CH2S)(CO)6] (Fe-adt) in acetonitrile. The proposed mechanism is fully consistent with the observed dependence of the voltammetric responses on the strength of the acid used as a proton source. Addition of moderately strong acids, such as CCl3CO2H (pK(a) = 10.7) or HOTs·H2O (pK(a) = 8.6), triggers the occurrence of new reduction events at potentials less negative than the reduction of Fe-adt, therefore ascribed to reduction of the protonated forms of the complex. Reduction of the N-protonated form seems to favor a tautomerization reaction leading to a Fe-H intermediate. On the other hand, addition of weak acids, such as ClCH2CO2H (pK(a) = 15.3), leads to direct protonation on the diiron site subsequently to reduction of the catalyst. A better understanding of the mechanism of proton reduction by the biologically relevant Fe-adt derivative could impact the design of improved catalysts inspired by FeFe-hydrogenase.

A Mechanistic Study of the Spontaneous Hydrolysis of Glycylserine as the Simplest Model for Protein Self‐Cleavage

A common feature of several classes of intrinsically reactive proteins with diverse biological functions is that they undergo self-catalyzed reactions initiated by an N→O or N→S acyl shift of a peptide bond adjacent to a serine, threonine, or cysteine residue. In this study, we examine the N→O acyl shift initiated peptide-bond hydrolysis at the serine residue on a model compound, glycylserine (GlySer), by means of DFT and ab initio methods. In the most favorable rate-determining transition state, the serine COO(-) group acts as a general base to accept a proton from the attacking OH function, which results in oxyoxazolidine ring closure. The calculated activation energy (29.4 kcal mol(-1) ) is in excellent agreement with the experimental value, 29.4 kcal mol(-1) , determined by (1) H NMR measurements. A reaction mechanism for the entire process of GlySer dipeptide hydrolysis is also proposed. In the case of proteins, we found that when no other groups that may act as a general base are available, the N→O acyl shift mechanism might instead involve a water-assisted proton transfer from the attacking serine OH group to the amide oxygen. However, the calculated energy barrier for this process is relatively high (33.6 kcal mol(-1) ), thus indicating that in absence of catalytic factors the peptide bond adjacent to serine is no longer a weak point in the protein backbone. An analogous rearrangement involving the amide N-protonated form, rather than the principle zwitterion form of GlySer, was also considered as a model for the previously proposed mechanism of sea-urchin sperm protein, enterokinase, and agrin (SEA) domain autoproteolysis. The calculated activation energy (14.3 kcal mol(-1) ) is significantly lower than the experimental value reported for SEA (≈21 kcal mol(-1) ), but is still in better agreement as compared to earlier theoretical attempts.

Conformational studies of diosgenyl 2-amino-2-deoxy-β-d-glucopyranosides at the PM3 and DFT levels of theory

Geometry optimizations at the PM3 level were performed for diosgenyl 2-amino-2-deoxy-β-d-glucopyranoside and its N-protonated form. Next, B3LYP/6-311++G∗∗ level geometry optimizations were carried out, albeit on a simpler model. The relative Gibbs free energies and geometry parameters are presented for the optimized structures. Conformational analysis concerning the clockwise (cw) and counterclockwise (ccw) arrangements of the OH groups as well as the three orientations of the NH2 and CH2OH groups was performed. Furthermore, a full scan of all the possible locations of the diosgenyl moiety in relation to the sugar ring in the target compounds was done. The PM3 optimization results indicate that diosgenyl 2-amino-2-deoxy-β-d-glucopyranoside exists as a mixture of many rotamers. Of these, ccw conformers as well as the −ac orientation of the aglycone (ca −100° for torsion angle ϕ) are preferred. In the case of the N-protonated glucoside one rotamer is dominant in the mixture (population>60%). Only the cw arrangement is stable in the protonated form, because of steric and electronic repulsion between the charged ammonium group and the hydrogen atom of the neighbouring 3-OH group. The gauche-trans (gt) orientation of the CH2OH group is favourable to both neutral and protonated forms of diosgenyl glucosides at the PM3 level. DFT studies also predict conformational mixtures for both neutral and protonated forms of simplified diosgenyl 2-amino-2-deoxy-β-d-glucopyranosides. These investigations showed unequivocally the preference for the ccw arrangement over cw, and that values of angle ϕ concur with the exo-anomeric effect. The B3LYP functional predicts the greater stability of the gt and tg orientations for the neutral and protonated analogues respectively. According to both PM3 and B3LYP calculations, torsion angle ψ has only a minor influence on the conformational energy. The importance of the geometry parameters affecting the stability of these conformers appears to be as follows: angle ϕ≈NH2/ccw/cw>gg/gt/tg>angle ψ.

Synthesis and photochromic properties of novel pyridine-containing diarylethenes

Abstract Three isomeric pyridine-containing diarylethenes were synthesized to study the effects of nitrogen atom position ( ortho , para , meta ) on their photochromic properties. Among these diarylethenes, the example with the nitrogen atom at the ortho -position of pyridine displayed the largest absorption maximum and molar absorption coefficients. The cyclization quantum yields increased in order of para meta ortho , whereas their cycloreversion quantum yields decreased in order of para > meta > ortho . Compared to the diarylethene with terminal phenyl ring, those with a terminal pyridine showed enhanced cyclization quantum yields and emission intensities. Moreover, these pyridine-containing diarylethenes exhibited multi-addressable switching behavior under the stimulation of both proton and light. Addition of trifluoroacetic acid to the solutions of the diarylethenes resulted in notable color change, and their N-protonated forms also possessed excellent photochromism. These results indicated that the nitrogen atom position played a pivotal role in the process of photoisomerization of the diarylethenes.

Transformations of the Vaska-type complex trans-[RhCl(CO)(PTA) 2] (PTA = 1,3,5-triaza-7-phosphaadamantane) during stepwise addition of HCl: Synthesis, characterization and crystal structure of trans-[RhCl 2(PTA)(PTAH)

The new aqua-soluble rhodium(I) complex trans-[RhCl 2(PTA)(PTAH)] ( 1) {PTAH = N-protonated form of 1,3,5-triaza-7-phosphaadamantane (PTA)} has been synthesized via the reaction of trans-[RhCl(CO)(PTA) 2] with aqueous HCl or N-chlorosuccinimide, or by the treatment of RhCl 3 with PTA. Compound 1 has been characterized by IR, 1H and 31P{H} NMR spectroscopies, ESI–MS(+), elemental and single crystal X-ray diffraction analyses, the latter showing a square planar {RhCl 2P 2} geometry. Besides, the stepwise addition of diluted HCl to an aqueous solution of trans-[RhCl(CO)(PTA) 2] has been monitored by 31P{ 1H} NMR and ESI–MS(+) techniques, allowing to detect a number of intermediate Rh(I) species.

Some physicochemical properties of the antitumor drug thiotepa and its metabolite tepa as obtained by density functional theory (DFT) calculations

Density functional theory (DFT) using the B3LYP functional was applied to elucidate the molecular properties of the antitumor drug thiotepa and its main metabolite tepa. Aqueous solvent effects were introduced using the conductor-like polarizable continuum model (CPCM). The protocol for calculating the pK (a) values obtained with different cavity models was tested on a series of aziridine and phosphoramide compounds. An efficient computational scheme has been identified that uses the CPCM model of solvation with a universal force field (UFF) cavity. The method has been used to evaluate the basicities of thiotepa and its metabolite. Our calculations show that the basicities of the aziridine moiety of thiotepa and tepa are dramatically reduced compared to free aziridine, indicating that highly acidic media are needed to produce substantial yields of the N-protonated form of the drug. Finally, the mechanisms of reaction of the drug and its metabolite are discussed based on our theoretical results. The calculations reproduce the experimental trends very satisfactorily.

Engineering Coordination and Supramolecular Copper−Organic Networks by Aqueous Medium Self-Assembly with 1,3,5-Triaza-7-phosphaadamantane (PTA)

The aqueous medium self-assembly reactions of copper(II) nitrate with 1,3,5-triaza-7-phosphaadamantane (PTA) as a main ligand and sodium azide or iodide as an auxiliary ligand lead to the new water-soluble Cu(I) coordination polymer [Cu(μ-N3)(μ-PTA)]n (1) and monomer [CuI(PTA)(PTAH)2]I2·H2O (2) (PTAH = N-protonated form of PTA), with the PTA cages exhibiting the rare P,N- or the conventional P-coordination mode, respectively. Another hydrosoluble P-bound PTA derivative [Cu(PTA)4](NO3)·6H2O (3) is furnished in the absence of any auxiliary ligand. The compounds have been characterized by IR and NMR spectroscopy, elemental and single crystal X-ray diffraction analyses which feature the formation of a unique one-dimensional (1D) coordination network in 1 composed of the {Cu2(μ-N3)2} cores and PTA spacers, as well as 1D (in 2) and three-dimensional (3D) (in 3) supramolecular structures built from multiple N−H···N (PTAH/PTA) and O−H···N (H2O/PTA) H-bonds, respectively. The study broadens the still limited use of PTA as a spacer or building block for crystal engineering of metal−organic coordination and supramolecular networks, their nature being also dependent on the type of auxiliary ligand. Compound 1 represents the first example of a copper coordination polymer with PTA.

Protophilicity, electrochemical property, and desulfurization of diiron dithiolate complexes containing a functionalized C 2 bridge with two vicinal basic sites

Two diiron dithiolate complexes [{μ-SC(NBn)CH(NHBn)S-μ}Fe 2(CO) 5L] (L = PPh 3, 2; P(Pyr) 3, 3) containing a functionalized C 2 bridge with two vicinal basic sites were prepared and characterized as models of the FeFe-hydrogenase active site. The molecular structures of 2 and its N-protonated form [( 2H N)(OTf)] were determined by X-ray analyses of single crystals. In the solid state of [( 2H N)(OTf)]. Each asymmetric unit contains a molecule of [( 2H N)(OTf)] and a molecule of water. The molecule of water is close to the iron atom of the [Fe(CO) 3] unit (Fe···O(H 2O), 4.199 Å). The complexes 2 and 3 are relatively protophilic. 31P NMR spectra and cyclic voltammograms show that they can be protonated by the mild acids CCl 3COOH and CF 3COOH. Electrochemical studies show that the first reduction peak of 3 at −1.51 V versus Fc +/Fc is 110 mV more positive than that (−1.62 V) found for the analogous diiron azadithiolate complex [{(μ-SCH 2) 2N(CH 2C 6H 5)}Fe 2(CO) 5P(Pyr) 3] ( 7). Protonation of 2 and 3 leads to the anodic shifts of 610–650 mV for the Fe IFe I/Fe IFe 0 reduction potentials. The shifts are apparently larger than that (450 mV) for protonation of 7. The reaction of the all-carbonyl complex [{μ-SC(NBn)CH(NHBn)S-μ}Fe 2(CO) 5L] with two equivalents of bis(diphenylphosphino)methane (dppm) in refluxing toluene affords a desulfurized complex [(μ-S)(μ-dppm) 2Fe 2(CO) 4] ( 6). The reaction process was studied. A dppm mono-dentate intermediate [{μ-SC(NBn)CH(NHBn)S-μ}Fe 2(CO) 5(κ 1-dppm)] ( 4) and a dppm μ-bridging species [{μ-SC(NBn)CH(NHBn)S-μ}Fe 2(CO) 4(μ-dppm)] ( 5) have been isolated and spectroscopically characterized.

Influence of a Pendant Amine in the Second Coordination Sphere on Proton Transfer at a Dissymmetrically Disubstituted Diiron System Related to the [2Fe]H Subsite of [FeFe]H2ase

Studies of the protonation of [Fe2(CO)4(kappa2-PNP)(mu-pdt)] (1; PNP = (Ph2PCH2)2NCH3) by HBF4.Et2O showed that the nature of the reaction product depends on whether the reaction is conducted in acetone or in dichloromethane. In acetone, an N-protonated form, 2, is isolated. Tautomerization of 2 in CH2Cl2 gives rise to a mu-hydride species 3. Variable-temperature NMR experiments have been performed to clarify the processes involved.

Competitive H-bonds in vacuo and in aqueous solution for N-protonated adrenaline and its monohydrated complexes

The conformational landscape of the N-protonated form of adrenaline (epinephrine in the U.S.) has been considered at both the B3LYP/6-31G* and 6-311++G** levels, with full geometry optimization in the gas phase and in aqueous solution, using the integral equation formalism for the polarizable continuum model (IEF-PCM). All stable orientations of the two catecholic hydroxy groups as well as the interconversion pathways between them have been taken into account. The dependence of the potential energy profile for the −[NH 2CH 3] + group rotation on the catechol ring and side-chain OH group orientation has been also examined. B3LYP/6-31G* stationary points have been confirmed with frequency calculations (at 310 K and 1 atm) allowing thermal corrections and IR spectra to be evaluated. Basis set effects do not alter the relative stability of the various forms that is maintained also when MP2 correlation corrections are included. The role of the internal structures either embedding in aqueous solution the conformers kept rigid at their in vacuo geometries or allowing the structure to relax has been examined at the IEF-PCM/B3LYP/6-31G* and 6-311++G** levels and compared to the IEF-PCM/MP2/6-31G* results. In vacuo the G1 conformers are favored with respect to the T and G2 ones, while in water the stability ordering changes, T becoming significantly more stable than both gauche forms. This occurs even for the gas-phase structures, including or not thermal corrections. The addition of a single water molecule to N-protonated adrenaline caused the intramolecular H-bond within the side chain to weaken till formation of two H-bonds with water. This fact, coupled to the strain relaxation, further stabilized the G1 and T conformers. The maximum intensity of the IR spectra increases in solution, especially for monohydrated adducts, where a significant red shift in the vibration of the NH involved in a H-bond to the water O is found.

B 12H 11-containing guanidinium derivatives by reaction of carbodiimides with H 3N–B 12H 11(1−). A new method for connecting boron clusters to organic compounds

The reaction of B 12H 11NH 3(1−) with carbodiimides can form guanidinium salts containing the boron cluster. Depending on the side chains of the carbodiimide, these derivatives of the B 12H 12(2−) cluster can be uncharged or can carry an overall positive or negative charge. This reaction allows the preparation of B 12 H 11 NH 3 - derivatives with aliphatic side chains, in contrast to the acylation reaction of B 12 H 11 NH 3 - and the formation of Schiff bases, both of which are successful only with aromatic acid chlorides or aromatic, respectively, α,β-unsaturated aldehydes. The acylation of B 12 H 11 NH 3 - with benzoyl chloride gives an N-protonated form of an imidoacid, carrying a single overall charge.

On the Applicability of Resonance Forms in Pyrimidinic Bases. II. QTAIM Interpretation of the Sequence of Protonation Affinities

The atomic properties of neutral and protonated forms of uracil and some model compounds, computed from B3LYP/6-31++G//B3LYP/6-31G charge densities with the QTAIM theory, indicate that sigma electron reorganization plays a significant role in the protonation processes. This reorganization is substantially different for O=C-C=C and O=C-C-X (X = N, O) units, involving transfers of electron population between all atoms in the first case but not across the C-X bond in the second unit. O-Protonation is basically favored over the N-protonation because of the lower electron population transferred to the proton. The stability sequence of N-protonated forms can be rationalized in terms of the closer position of the proton, when attached to N3, to regions of larger electron population (carbonyl groups).

Decomposition of protonated noradrenaline and normetanephrine assisted by NH2 migration studied by electrospray tandem mass spectrometry and molecular orbital calculations

As part of a research program on neurotransmitters in a biological fluid, the fragmentations characterising catecholamines protonated under electrospray ionisation (ESI) conditions, under low collision energy in a triple-quadrupole mass spectrometer, were investigated. The decompositions of protonated noradrenaline (VH) and normetanephrine (VIH) were studied. Both precursor ions eliminate first H2O at very low collision energy, and the fragmentations of [MH-H2O]+ occur at higher collision energy. The breakdown graphs of [MH-H2O]+ ions, with collision energy varying from 0-40 eV in the laboratory frame, are presented. [VIH-H2O]+ ions lose competitively NH3 and CH3OH. For [VH-H2O]+ the loss of NH3 is dominant while H2O is eliminated at very low abundance at all collision energies. All of these secondary fragmentations are followed at higher collision energies by elimination of CO. These fragmentations are interpreted by means of ab initio calculations up to the B3LYP/6-311+G(2d,2p) level of theory. The elimination of H2O requires first the isomerisation of N-protonated forms, chosen as energy references, to O-protonated forms. The isomerisation barriers are calculated to be lower than 81 kJ/mol above the N-protonated forms. The elimination of NH3 from [MH-H2O]+ requires first the migration, via a cyclisation, of the amine function from the linear chain to the aromatic ring in order to prevent the formation of unstable disubstituted carbocations in the ring. The barriers associated with the loss of NH3 are located 220 and 233 kJ/mol above VH and 219 kJ/mol above VIH. The energy barrier for the loss of ROH is located 236 and 228 kJ/mol above VH and VIH, respectively. The absence of ions corresponding to [VH-2H2O]+ is due to a parasitic mechanism with an activation barrier lower than 236 kJ/mol that leads to a stable species unable to fragment, thus preventing the second loss of H2O. Losses of CO following the secondary fragmentations involve activation barriers higher than 330 kJ/mol.

Ab Initio MR-CISD Study of Gas-Phase Basicity of Formamide in the First Excited Singlet State

MR-CISD and MR-CISD+Q calculations have been carried out to investigate geometries, energies, and electronic absorption spectra of formamide and its O- and N-protonated forms. The vertical excitation energies for formamide are in good agreement with available experimental data and with the results of best calculations reported so far. Analysis of the calculated electronic absorption spectra reveals that the lowest excited state in the parent molecule and in its N-protonated form corresponds to the n−π* valence excited state, whereas the O-protonated form shows the π−π* excited valence state as the lowest one. The second excited valence states in the neutral molecule and the N-protonated ion are the π−π* state, whereas it is the n−π* state for the O-protonated formamide. Adiabatic excitation energies are reported for the first excited valence state of all three species with structures optimized at the MR-CISD level. All structures exhibit strong deviation from planarity characterized by pyramidalization of the C and the N atoms and rotation of the NH2 with respect to the plane of the COH group. It appears that oxygen is the most basic site of formamide both in the ground state and in the first singlet excited state. Its calculated gas-phase basicity (GB) and proton affinity (PA) in the latter are smaller than in the ground state by 2.1 kcal mol-1 and 2.4 kcal mol-1, respectively. The difference in basicity between oxygen and nitrogen positions drops from 16 kcal mol-1 (ground state) to 6 kcal mol-1 (first singlet excited state). These results are analyzed within the Förster thermodynamic cycle.

Synthesis, structure and redox potentials of biologically active ferrocenylalkyl azoles

The syntheses, structures, electrochemical properties of the series of ferrocenylalkyl azoles, FcAlkAz, as well as the antitumor activity of ferrocenylmethyl benzimidazole ( 8) have been studied. Above mentioned compounds were investigated by the method of cyclic voltametry. All of them exhibited a reversible one-electron oxidation–reduction wave owing to the ferrocene–ferrocenium redox couple with a positive shift (0.50–0.65 V) compared with that of ferrocene (0.42 V). The X-ray determination of molecular structures of 1-(ferrocenylmethyl)imidazole ( 4), 1-(ferrocenylbenzyl)imidazole ( 7) and 1-(ferrocenylmethyl)bezimidazole ( 8) was carried out. Compound 4 with imidazolyl substituent was found to be present in N-protonated form. Antitumor activity of 1-(ferrocenylmethyl)benzimidazole ( 8) against some solid tumor models such as adenocarcinoma 755 (Ca755), melanoma B16 (B16) and Lewis lung carcinoma was studied. The antitumor activity of compound 8 was compared with cisplatin effectiveness against some experimental tumor systems.

Protonation of N-alkenylacrylamides

Protonation of N-alkenylacrylamides and medium effects on the protonation direction were studied theoretically (DFT calculations) and experimentally (IR spectroscopy). In crystal, N-alkenylacrylamide hydrochlorides exist in the O-protonated form in contrast to acrylamide hydrochloride which exists in the N-protonated form.