The deprotonation and protonation equilibria of a hypericin derivative in aqueous solution

Summary A hypericin derivative ,'-appended at the methyl groups with two polyethylene glycol moieties (about 23 units long) and capped with acetyl groups was synthesized starting from emodin. This derivative proved to be soluble in water and was investigated by means of spectrophotometric titrations and electrophoresis experiments. Deprotonation at thebay-region hydroxyl group was observed atpK _a=1.6. This was followed by a second deprotonation step of aperi-hydroxyl group at apK _a value of 9.4. This derivative could be protonated at the carbonyl group characterized by apK _a value of –5.7. FrompK _a determinations in water-ethanol mixtures the correspondingpK _a values of hypericin itself determined in such mixtures were extrapolated to the aqueous phase. This resulted in estimatedpK _a values of 1.8, 9.2, and –6.

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Deprotonierungs- und Protonierungsgleichgewichte eines Hypericinderivates in wäßriger Lösung

Zusammenfassung Ein an den Methylgruppen von Hypericin mit endständig acetylierten Polyethylenglykolketten (ungefähr 23 Einheiten lang) ,'-disubstituiertes Derivat wurde ausgehend von Emodin synthetisiert. Dieses Derivat ist wasserlöslich, und es wurde mit Hilfe von spektrophotometrischen Titrationen und Elektrophorese untersucht. Die Deprotonierung derbay-Hydroxylgruppe erfolgt beipK _a=1.6. Diese wird von einem zweiten Deprotonierungsschritt an einerperi-Hydroxylgruppe bei einempK _a-Wert von 9.4 gefolgt. Dieses Derivat konnte an der Carbonylgruppe protoniert werden, was durch einenpK _a-Wert von –5.7 charakterisiert ist. Ausgehend vonpK _a-Messungen in Wasser-Ethanol-Mischungen wurden die entsprechendenpK _a-Werte auch für das Hypericin selbst in wäßriger Phase extrapoliert. Dies führte zu geschätztenpK _a-Werten von 1.8, 9.2 und –6.

     

Conformational and electronic properties of a microperoxidase in aqueous solution: a computational study.

A theoretical study of the conformational properties of a small heme peptide in aqueous solution is carried out by classical, long-timescale molecular dynamics simulations. The electronic properties of this species, that is, the relative energies of its excited electronic states and the redox potential, are reproduced and related to the conformational behavior using the perturbed matrix method and basic statistical mechanics. Our results show an interesting coupling between the conformational transitions and the electronic properties. These investigations, beyond the biophysically relevant results addressing the long-standing question of the actual role of the enzyme structure on the enzyme activity, are also of some methodological interest since they offer a further computational perspective for including the electronic degrees of freedom into the modeling of rather complex molecular systems.     

A radiotracer study of adsorption on activated carbon cloth from aqueous solution

A study has been made on the effect of pH upon the equilibrium adsorption capacity of triethyl phosphate, dimethyl phosphate and orthophosphate on to activated carbon cloth. It is shown that for molecular phosphates no dependence upon pH exists, whilst the adsorption of ionic phosphates exhibit a strong pH dependence. These adsorption trends may be explained in terms of pKa values, ionic strength and the surface charge of the activated carbon cloth is aqueous solution.     

A computational study of intramolecular proton transfer in gaseous protonated glycine

The minimum energy paths for intramolecular proton transfer between the amino nitrogen and carbonyl oxygen atoms in gaseous protonated glycine were estimated at the Hartree-Fock (HF) and second-order M?ller-Plesset Perturbation (MP2) levels of theory. Potential energy profiles and their associated reactant, transition state, and product species calculated at the MP2/6-31G* level were shown to differ significantly from those obtained at the HF/6-31G* level. Effects of electron correlation and basis functions on the calculated geometries and energies of relevant species were examined at the HF, MP2, MP4, CCSD, and B3LYP levels using the 6-31G*, 6-31G**, 6-31+G**, 6-311+G**, 6-31+G(2d,2p), 6-311+G(3df,2p), cc-pVDZ, aug-cc-pVDZ, and cc-pVTZ basis sets. The HF and MP2 optimized levels with the 6-31G*, 6-31G**, 6-31+G**, and 6-311+G** bases were used to calculate the thermodynamic and kinetic properties of the proton transfer reaction at 298.15 K and 1 atm, which include enthalpy, entropy, Gibbs free energy, equilibrium constant, potential energy barriers, tunneling transmission coefficients, and rate constants. Results indicate that the proton in a carbonyl O-protonated glycine undergoes a rapid migration to the amino nitrogen atom, while the reverse process is extremely unfavorable. The objective of this work is to develop practical theoretical procedures for studying proton transfer reactions in amino acids and peptides and to assemble physical data from these model calculations for future references.     

Enantioselective organocatalytic intramolecular Diels-Alder reactions: a computational study

The diastereo- and enantioselectivity obtained experimentally by Christmann in the amine-catalyzed intramolecular Diels-Alder reaction of α,β-unsaturated carbonylic compounds were fully rationalized using density functional theory methods at the PBE1PBE/6-311+G** level. A polarizable continuum model was used to describe solvent effects. The selectivity is induced in the cyclization step, and while the enantioselectivity results from the syn/anti orientation around the C-N enamine bond, the diastereoselectivity mainly results from the syn/anti configuration of the substituents in the forming cyclopentane ring. The remarkable reaction rate experimentally observed when an external protic acid is used is attributed to the strong decrease in the activation energy of all steps needed for the enamine formation, while the external acid marginally influences the cyclization step. When hydrogen-bond-donor catalysts are used, the formation of one hydrogen bond in the cyclization step inverts the configuration and reduces the selectivity. The different behavior between dialdehydes and ketoaldehydes is suggested to be resulting from different reaction rates in the catalyst elimination step.     

Removal of 2.4-dichloro phenoxyacetic acid from aqueous solution by adsorption on activated carbon. A kinetic study

The sorption of 2.4-dichloro phenoxyacetic acid (2.4-D) on two different activated carbons was determined using the batch equilibration technique. The calculated slopes of the Freundlich sorption isotherms were significantly less than 1. The (K) values were higher for the activated carbon which has the higher specific surface, and increased with NaCl concentration. The rate of attaining equilibrium of 2.4-D increased with a decrease in absorbent concentration. Dynamic modelling of the adsorption showed that a first order reversible kinetic model was followed for the adsorption process. The overall rate constant K′, the adsorption rate K₁, the desorption rate constant K₂, and the equilibrium constant K_c for the adsorption process were calculated.     

Aminium cation radical of glycylglycine and its deprotonation to aminyl radical in aqueous solution

The photochemical reaction between glycylglycine and triplet 4-carboxybenzophenone has been investigated using time-resolved chemically induced dynamic nuclear polarization (CIDNP). It is shown that the mechanism of the peptide reaction with triplet excited carboxybenzophenone is electron transfer from the amino group of the peptide, leading to the formation of an aminium cation radical that deprotonates to a neutral aminyl radical. Simulation of the CIDNP kinetics leads to an estimation of the paramagnetic relaxation time for the alpha-protons at the N-terminus at 20 to 40 mus with the best-fit value of 25 mus.     

Electrochemical study on the keto-enol tautomerization of p-hydroxyphenylpyruvic acid in aqueous solution

The keto-enol tautomerization of p-hydroxyphenylpyruvic acid (pHPP) in aqueous solutions and the complexation reaction between enolic pHPP and boric acid have been studied by electrochemical techniques including linear sweep voltammetry (LSV), pulse voltammetry, and cyclic voltammetry (CV), combining with UV spectrometry. Electrochemical techniques reveal that in aqueous solution, there are two tautomers of pHPP: enolic form and ketonic form; the former exists mainly in freshly prepared pHPP solution, and the latter exists mainly in equilibrium solution. Both enolic and ketonic pHPP are electroactive. The electrochemical oxidation of enolic pHPP gives rise to two anodic waves, I(a) and II(a), while the electrochemical oxidation of ketonic pHPP only results in the observation of the second wave II(a). The oxidation process I(a) is revealed to be associated with the quasi-reversible, two-electron two-proton oxidation of "C=C"group at the side chain of enolic pHPP, and the oxidation process II(a) is proposed to result from the irreversible oxidation of phenolic hydroxyl group. It is observed that in aqueous solution, enolic pHPP can quickly complex with boric acid to yield enol-borate complex that can also oxidize at a glassy carbon electrode to yield an anodic wave.     

Spectroscopic and optimization modeling study of nitrous acid in aqueous solution

Nitrous acid (HONO) and the nitrite ion represent a particularly important conjugate pair of trace species with regard to heterogeneous behavior within the bulk, and on the surface, of aqueous atmospheric dispersions: this role results from their chemical reactivity, photolysis pathways, solubility, and ambient concentration levels. The actual ratio of NO(2)(-): HONO in solution is determined by the pH and the nitrous acid dissociation constant (pK(a)) which is generally quoted in the literature as 3.27 at 298 K. However there is much disagreement in published works as to the exact value, which should be used in model calculations relevant to the atmosphere. Furthermore even though the nitrite ion is known to absorb solar radiation in the 300-400 nm region and represents a dominant source of *OH radicals in surface seawater, large variations in the measured molar decadic absorption coefficients, epsilon, for nitrite ions (and aqueous HONO) are evident in the literature. In the current study, using a UV-vis spectrometric approach with careful baseline subtraction, the relevant epsilon values for the nitrite ion were determined to be 8.16 +/- 0.08 M(-1) cm(-1) for the npi transitions at 290 nm and 22.1 +/- 0.22 M(-1) cm(-1) at 354 nm. For HONO, the wavelength maximum for the strongest vibronic band in solution was found at 372 nm with an epsilon value of 60.52 +/- 0.6 M(-1) cm(-1). Using the Henderson-Hasselbalch equation and the above data, a value of 2.8 +/- 0.1 is therefore reported here for the pK(a) of nitrous acid. A Newton-Gauss method was then employed to solve a set of nonlinear equations defining the chemical speciation model for HONO in solution using an algorithm written in FORTRAN 90. A model based on a simple one-step protonation worked well for intermediate pHs (6-3) but departed from the experimental observations in highly acidic media. A two-step equilibrium model involving the nitroacidium ion, H(2)ONO(+), gave a much closer fit in the very acidic region, while having little or no effect on the pH 6-3 section of the profile.     

Theoretical study of the kojic acid structure in gas phase and aqueous solution

Density functional calculations at the B3LYP/6‐311++G** level have been performed to determine the ground‐state conformational preference for kojic acid, a widely used skin‐whitening, antibrowning, and antibacterial agent. It is found that the gas phase consists almost entirely of the 5‐hydroxy‐2‐(hydroxymethyl)‐4H‐pyran‐4‐one tautomer, although several rotamers of this are prevalent. In aqueous solution, however, other tautomers are also present. The validity of the calculations is confirmed by the observed FTIR, NMR, and UV–vis spectra, which show good correspondence with the theoretical spectra. The electronic interactions are interpreted in terms of charge and bond order analysis as well as the composition of the HOMO and LUMO. The calculations show that kojic acid has partial aromatic character and is a good nucleophile. © 2011 Wiley Periodicals, Inc. Int J Quantum Chem, 2011     

Insight into the adsorption of dyes onto chitin in aqueous solution: An experimental and computational study

This study aimed to get an insight into the adsorption of three synthetic dyes onto chitin using experimental and computational approaches. The successful preparation of α-chitin was confirmed using the Fourier Transform Infrared (FTIR) and X-ray Diffraction (XRD). In addition, the presence of porous and fiber on the surface of the extracted chitin was revealed by the Scanning Electron Microscopy (SEM) analysis. The extracted α-chitin was then used as an adsorbent to remove synthetic dyes, namely Malachite green, Basic red 18, and Alizarin yellow R. The kinetic study showed that the adsorption of dyes was well-described using a pseudo-second-order model, whereas the isotherm adsorption obeyed the Freundlich model. The Frontier Molecular Orbital (FMO) revealed several locations of dyes and chitin molecules that are potentially active sites for adsorption. The adsorption trend could be related to the Highest Occupied Molecular Orbital (HOMO) – Lowest Unoccupied Molecular Orbital (LUMO) energy gap and electrophilicity index of the dyes. The Conductor-like Model for Real Solvent (COSMO-RS) model demonstrated, for the first time, that several interactions occurred during the adsorption of dyes onto α-chitin. For the Malachite green and Basic Red 18, the Van der Waals forces of the dyes controlled its adsorption behavior. In contrast, the hydrogen bonding interaction governed the adsorption behavior of Alizarin yellow R dye onto α-chitin. The gathered insight from this work might guide us better to understand the molecular level of dyes–chitin interactions and, ultimately, to design adsorbents to remove synthetic dyes from wastewater.     

Complexation of uranium(VI) with aromatic acids in aqueous solution: a combined computational and experimental study

The complexes of uranium(VI) with salicylhydroxamate, benzohydroxamate, and benzoate have been investigated in a combined computational and experimental study using density functional theory methods and extended X-ray absorption fine structure spectroscopy, respectively. The calculated molecular structures, relative stabilities, as well as excitation spectra from time-dependent density functional theory calculations are in good agreement with experimental data. Furthermore, these calculations allow the identification of the coordinating atoms in the uranium(VI)-salicylhydroxamate complex, i.e. salicylhydroxamate binds to the uranyl ion via the hydroxamic acid oxygen atoms and not via the phenolic oxygen and the nitrogen atom. Carefully addressing solvation effects has been found to be necessary to bring in line computational and experimental structures, as well as excitation spectra.     

New insights on the nature of the chemical species involved during the process of dopamine deprotonation in aqueous solution: theoretical and experimental study

Due to dopamine's chemical structure and the fact that it has three pKa values, its deprotonation process, in aqueous solution, may involve different chemical species. For instance, the first deprotonation step, from the fully protonated dopamine molecule (H3DA+) to the neutral one (H2DA), will result in zwitterionic species if a proton from one of the OH groups in the catechol ring is lost or into a neutral species if the proton is lost from the amino group. Given that the interaction of such a product with its environment will be quite different depending on its nature, it is very important, therefore, to have an accurate knowledge of which is the dopamine chemical species that results after each deprotonation step. In order to gain a better understanding of dopamine chemistry and to establish a plausible dopamine deprotonation pathway, the optimized geometries of the aforementioned species were calculated in this work by means of the density functionals theory (B3LYP/6-311+G(d,p)) in both cases: in vacuo and with solvent effect, to assess, among other theoretical criteria, the proton affinities of the different dopamine species. This permitted us to propose the following reaction pathway: [reaction in text]. Moreover, the calculations of the chemical shift (NMR-GIAO) modeling the effect of the solvent with a continuum method (PCM) was in agreement with the 13C NMR experimental spectra, which confirmed even further the proposed deprotonation pathway.     

Excited-state hydrogen bonding and deprotonation of esculetin in solution: a DFT/TDDFT study

The combined density functional theory (DFT) and time-dependent density functional theory (TDDFT) method was used to study the electronic spectral properties of different deprotonated forms of esculetin. By comparing the experimental absorption and fluorescence bands with the calculated electronic spectra, it is evidently demonstrated that the minor absorption and fluorescence bands observed at slightly longer wavelengths than the principal bands in experiments are predominantly from the de-H3 form of the esculetin monomer. Furthermore, we clarified the relationship between electronic spectral shifts and electronic excited-state intramolecular hydrogen bonding changes: the strengthening of intramolecular hydrogen bond can induce an electronic spectral blueshift while the intramolecular hydrogen bond weakening can result in an electronic spectral redshift.     

Spectroscopic and computational studies of aqueous ethylene glycol solution surfaces

The combination of Monte Carlo, ab initio, and DFT computational studies of ethylene glycol (EG) and EG-water hydrogen-bonding complexes indicate that experimental vibrational spectra of EG and EG-water solution surfaces have contributions from numerous conformations of both EG and EG-water. The computed spectra, derived from harmonic vibrational frequency calculations and a theoretical Boltzmann distribution, show similarity to the experimental surface vibrational spectra of EG taken by broad-bandwidth sum frequency generation (SFG) spectroscopy. This similarity suggests that, at the EG and aqueous EG surfaces, there are numerous coexisting conformations of stable EG and EG-water complexes. A blue shift of the CH2 symmetric stretch peak in the SFG spectra was observed with an increase in the water concentration. This change indicates that EG behaves as a hydrogen-bond acceptor when solvated by additional water molecules. This also suggests that, in aqueous solutions of EG, EG-EG aggregates are unlikely to exist. The experimental blue shift is consistent with the results from the computational studies.     

Dynamic nature of the intramolecular electronic coupling mediated by a solvent molecule: a computational study

We present a combined Molecular Dynamics/Quantum Chemical study of the solvent-mediated electronic coupling between an electron donor and acceptor in a C-clamp molecule. We characterize the coupling fluctuations due to the solvent motion for different solvents (acetonitrile, benzene, 1,3-diisopropyl-benzene) for the charge separation and the charge recombination processes. The time scale for solvent-induced coupling fluctuation is approximately 0.1 ps. The effect of these fluctuations on the observed rate is discussed using a recently developed theoretical model. We show that, while the microscopic charge transfer process is very complicated and its computational modeling very subtle, the macroscopic phenomenology can be captured by the standard models. Analyzing the contribution to the coupling given by different solvent orbitals, we find that many solvent orbitals mediate the electron transfer and that paths through different solvent orbitals can interfere constructively or destructively. A relatively small subset of substrate-solvent configurations dominate contributions to solvent-mediated coupling. This subset of configurations is related to the electronic structure of the C-clamp molecule.     

Chiral diamines 4: a computational study of the enantioselective deprotonation of Boc-pyrrolidine with an alkyllithium in the presence of a chiral diamine

The enantioselective deprotonation of N-Boc-pyrrolidine (1) with i-PrLi-(-)-sparteine has been studied at theoretical levels up through B3P86/6-31G. Four low-energy intermediate complexes involving i-PrLi-(-)-sparteine and 1 were located via geometry optimizations; two of these complexes would lead to abstraction of the pro-S hydrogen from 1, and the other two complexes would lead to loss of the pro-R hydrogen. The lowest-energy intermediate complex was found to lead to loss of the pro-S hydrogen as observed experimentally. Transition states for the deprotonations were located using the synchronous transit-guided quasi-Newton method. The calculated activation enthalpy for transfer of the pro-S hydrogen within the lowest-energy intermediate complex, 10.8 kcal/mol, is reasonable for a reaction that occurs at a relatively low temperature, and the calculated kinetic hydrogen isotope effect is in agreement with experimental data. The lower enantioselectivity observed experimentally for deprotonation of 1 using t-BuLi-(-)-sparteine is attributed to a transition-state effect due to increased steric interaction engendered by the bulky t-BuLi. Replacement of the tert-butoxycarbonyl group in 1 by a methoxycarbonyl is predicted to result in a slower deprotonation with somewhat decreased enantioselectivity. Asymmetric deprotonation of 1 using i-PrLi in combination with the C(2)-symmetric diamine, (S,S)-1,2-bis(N,N-dimethylamino)cyclohexane, was calculated to be much less selective than is the deprotonation mediated by (-)-sparteine as observed experimentally. The relative energies of the intermediate complexes were fairly well-reproduced by ONIUM calculations in which the sparteine ligand less its nitrogen atoms was treated by molecular mechanics and the remainder of the complex was treated by quantum mechanics.     

Light-controlled single-walled carbon nanotube dispersions in aqueous solution

We have succeeded in dispersing single-walled carbon nanotubes (SWNTs) into an aqueous solution of poly(ethylene glycol)-terminated malachite green derivative (PEG-MG) through simple sonication. It was found that UV exposure caused reaggregation of these predispersed SWNTs in the same aqueous medium, as adsorbed PEG-MG photochromic chains could be effectively photocleavaged from the nanotube surface. The observed light-controlled dispersion and reaggragation of SWNTs in the aqueous solution should facilitate the development of SWNT dispersions with a controllable dispersity for potential applications.     

Aluminum speciation in biological environments. The deprotonation of free and aluminum bound citrate in aqueous solution

Citrate is the main low mass molecule chelator of aluminum in serum, and knowledge of the interaction mode of this organic molecule with this cation is necessary to understand aluminum speciation in biosystems. However, the 1?∶?1 complexation of citric acid to Al(iii) is a complex process due to the myriad of coordination sites and protonation states of this molecule. Moreover, due to the acidic character of the complex, its entire experimental characterization is elusive. The system is also challenging from a computational point of view, due to the difficulties in getting a balanced estimation of the large range of solvation free energies encountered for the different protonation states of a multiprotic acid in both situations, complexed and uncomplexed with a trivalent cation. Herein, the deprotonation process of the free citric acid in solution and that interacting with Al(iii) have been investigated considering all possible coordination modes and protonation states of the citric acid. All the structures were optimized in solution combining the B3LYP density function method with the polarizable continuum IEFPCM model. In addition, different schemes have been employed to obtain reliable solvation energies. Taking into account the most stable isomer of each protonation state, the pK(a) values were computationally estimated for the free citric acid and that interacting with Al(iii), showing a good agreement with the experimental data. All these results shed light on how the deprotonation process of the citric acid takes place, and show that Al(iii) not only increases the acidity of the molecule, but also changes qualitatively the deprotonation pattern of the citric acid. This information is highly relevant to understand aluminum speciation in biological environments, for which citrate is the main low molecular weight chelator, and responsible for its cellular in-take.