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European Journal of Pharmaceutical... Oct 2016The knowledge of the speciation of fluoroquinolones is of great actuality for the implications on the activity, bioavailability and pharmacokinetics. Literature reports...
The knowledge of the speciation of fluoroquinolones is of great actuality for the implications on the activity, bioavailability and pharmacokinetics. Literature reports a number of contrasting evaluations on the existence of tautomeric forms of mono-protonated species, described by a set of protonation micro-constants. Here the protonation sequence and the related protonation constants of four representative molecules are evaluated by a combined potentiometric-spectrophotometric method. The experimental observations necessary to differentiate between a protonation scheme represented by macro-constants alone, and the one that requires the introduction of a micro-protonation scheme, are clearly delineated based on a careful analysis of experimental data and of simulated models. The role of the medium was investigated and UV-vis spectra in water- methanol solution were analyzed. The existence of the zwitterionic species alone at physiological pH in water, and an increase of the relative amount of the neutral species with the lipophilicity of the medium were remarked. This surely affects the bioavailability of FQs, with the increase of the neutral species when the molecules approach the local lipophilic environment close to the cellular membranes. NMR studies allowed the attribution of the protonation sites of the different forms. Quantum chemical evaluation of all the possible existent forms with different protonation degrees and in different sites strongly substantiates the experimental results. The study of the relevant frontier molecular orbitals completed the detailed theoretical characterization of the species.
Topics: Anti-Bacterial Agents; Fluoroquinolones; Potentiometry; Protons; Spectrophotometry
PubMed: 27586021
DOI: 10.1016/j.ejps.2016.08.053 -
The Journal of Chemical Physics Jan 2014The CC2 (second order approximate coupled cluster method) has been applied to investigate protonation effect on electronic transition energies of 2-pyridone (2PY),...
The CC2 (second order approximate coupled cluster method) has been applied to investigate protonation effect on electronic transition energies of 2-pyridone (2PY), 2-pyridone dimer, and micro-solvated 2-pyridone (0-2 water molecules). The PE profiles of protonated 2-pyridone (2PYH(+)) as well as monohydrated 2PYH(+) at the different electronic states have been investigated. The (1)πσ∗ state in protonated species (2PYH(+)) is a barrier free and dissociative state along the O-H stretching coordinate. In this reaction coordinate, the lowest lying (1)πσ∗ predissociates the bound S1((1)ππ∗) state, connecting the latter to a conical intersection with the S0 state. These conical intersections lead the (1)ππ∗ state to proceed as predissociative state and finally direct the excited system to the ground state. Furthermore, in presence of water molecule, the (1)πσ∗ state still remains dissociative but the conical intersection between (1)πσ∗ and ground state disappears. In addition, according to the CC2 calculation results, it has been predicted that protonation significantly blue shifts the S1-S0 electronic transition of monomer, dimer, and microhydrated 2-pyridone.
Topics: Dimerization; Electrons; Models, Molecular; Protons; Pyridones; Quantum Theory; Water
PubMed: 24437885
DOI: 10.1063/1.4859255 -
Journal of Oleo Science 2013Hydrogen bonding between surfactant molecules plays an important role in self-assembly formation. For long alkyl chain amine oxide surfactants, the specific protonation...
Hydrogen bonding between surfactant molecules plays an important role in self-assembly formation. For long alkyl chain amine oxide surfactants, the specific protonation degree dependence of some solution properties has been considered to be due to hydrogen bonding between protonated and deprotonated species. In addition to this type of hydrogen bonding, we introduced a pyridyl group into an alkylamine oxide molecule as a new hydrogen-bonding site. The pyridyl group has three different structural isomers based on the position of the substituent. An amine oxide group in pyridylamine oxides was preferentially protonated. In addition, protonation of the pyridyl group revealed a pronounced substituent position effect on the critical micelle concentration, micellar size, and solubilization of oil-soluble dye into micelles. The intermolecular or intramolecular hydrogen bond formation could be controlled by altering the substituent position.
Topics: Amines; Hydrogen Bonding; Molecular Structure; Oxides; Protons; Pyridines; Solutions; Surface-Active Agents
PubMed: 23470439
DOI: 10.5650/jos.62.123 -
The Journal of Physical Chemistry. B Jul 2020Proteins involved in proton-/electron-transfer processes often possess "functional" aspartates/aspartic acids (Asp) with variable protonation states. The mechanism of...
Proteins involved in proton-/electron-transfer processes often possess "functional" aspartates/aspartic acids (Asp) with variable protonation states. The mechanism of Asp protonation-deprotonation within proteins is unclear. Two questions were asked-the possible types of determinants responsible for Asp protonation-deprotonation and the spatial arrangements of the determinants leading to selective stabilization. The questions were analyzed using nine different solvent models, which scanned the complete protein dielectric range, and four protein models, which illustrated the spatial arrangements around Asp, termed as "molecular association". The methods employed were quantum chemical calculations and constant pH simulations. The types of the determinants identified were charge-charge interaction, H bonding, dipole-π interaction, extended electronic conjugation, dielectric effect, and solvent accessibility. All solvent-exposed Asp [buried fraction (BF) less than 0.5] were aspartates, and buried Asp were either aspartic acids or aspartates, each having a different "molecular association". The exposed aspartates were stabilized via a H-bonding network with bulk water, buried aspartates via salt bridge or, minimum, two intramolecular H bonds, and buried aspartic acids via, minimum, one intramolecular H bond. An "acid-alcohol pair" (involving Ser/Thr/Tyr) was a common determinant to any "functional" buried aspartate/aspartic acid. Higher energy "molecular associations" observed within proteins compared to those within water, presumably, indicated easy molecular restructuring and alteration of the Asp protonation states during a protein-mediated proton/electron transfer.
Topics: Aspartic Acid; Electron Transport; Hydrogen Bonding; Protein Conformation; Protons; Water
PubMed: 32484348
DOI: 10.1021/acs.jpcb.0c02629 -
ELife Dec 2021Anion channelrhodopsin from (ACR1) has Asp234 (3.2 Å) and Glu68 (5.3 Å) near the protonated Schiff base. Here, we investigate mutant ACR1s (e.g., E68Q/D234N)...
Anion channelrhodopsin from (ACR1) has Asp234 (3.2 Å) and Glu68 (5.3 Å) near the protonated Schiff base. Here, we investigate mutant ACR1s (e.g., E68Q/D234N) expressed in HEK293 cells. The influence of the acidic residues on the absorption wavelengths was also analyzed using a quantum mechanical/molecular mechanical approach. The calculated protonation pattern indicates that Asp234 is deprotonated and Glu68 is protonated in the original crystal structures. The D234E mutation and the E68Q/D234N mutation shorten and lengthen the measured and calculated absorption wavelengths, respectively, which suggests that Asp234 is deprotonated in the wild-type ACR1. Molecular dynamics simulations show that upon mutation of deprotonated Asp234 to asparagine, deprotonated Glu68 reorients toward the Schiff base and the calculated absorption wavelength remains unchanged. The formation of the proton transfer pathway via Asp234 toward Glu68 and the disconnection of the anion conducting channel are likely a basis of the gating mechanism.
Topics: Anions; Biological Transport; Channelrhodopsins; Cryptophyta; HEK293 Cells; Humans; Mutation; Protons
PubMed: 34930528
DOI: 10.7554/eLife.72264 -
Journal of the American Chemical Society Jul 2012Our investigation of the phenylalanine/serine (Phe/Ser) protonated dimer suggests that the intermolecular interaction between the two amino acids is more complex than...
Our investigation of the phenylalanine/serine (Phe/Ser) protonated dimer suggests that the intermolecular interaction between the two amino acids is more complex than could have been anticipated from previous studies of similar systems. Isomer-specific infrared (IR) spectra, recorded at an internal temperature of ~10 K, demonstrate the presence of at least five isomers with nonzwitterionic structures. Moreover, isotopic substitution experiments provide evidence for different protonation sites among these isomers.
Topics: Dimerization; Isomerism; Phenylalanine; Protons; Serine; Spectrophotometry, Infrared
PubMed: 22708822
DOI: 10.1021/ja3023708 -
Journal of Mass Spectrometry : JMS Mar 2022The current research is constructed for considering the chemical ionization and dissociation of perindopril in the positive mode of corona discharge ion mobility...
The current research is constructed for considering the chemical ionization and dissociation of perindopril in the positive mode of corona discharge ion mobility spectrometry. Four product ion peaks are observed in the ion mobility spectrum of perindopril erbumine at the cell temperature of 473 K. These peaks are assigned through the obtained intensity variation analysis in the ion mobility spectra over the elapsed time accompanied by the calculations backed by the validated density functional theory (DFT). In this regard, the most stable ionic species associated with each peak and the corresponding reliable generation pathways are found by the well-confirmed meta hybrid density functional method, M06-2X. The peaks are assigned to the protonated perindopril and its dissociation products, including counter ion and the related fragment ions. However, the structures of the neutral perindopril in the gas phase are thoroughly assessed to find a more stable one. The predicted chemical ionization products by the theory are in excellent agreement with our presented experiment here. Theoretical evaluations demonstrated that the production of a fragment by dissociation process occurs when perindopril gets a proton from the ionization region. Also, without protons, there is no dissociation process. Therefore, our mechanism investigated here is the proton transfer one. All possible sites of perindopril are considered theoretically for protonation along with their possible reactions. In addition to the computed PES, the assigned ions for obtained spectra are confirmed by the computed equilibrium constants and rate constants. Our theoretical results show that the peak of the main fragment is for M-CH CH OH produced by a reaction pathway involving no barrier. This study opens new perspectives in interpreting large molecules spectra for future studies.
Topics: Ion Mobility Spectrometry; Ions; Perindopril; Protons
PubMed: 35233864
DOI: 10.1002/jms.4814 -
Journal of the American Chemical Society May 2012A model system for biological Rieske clusters that incorporates bis-benzimidazolate ligands ((Pr)bbim)(2-) has been developed ((Pr)bbimH(2) =...
A model system for biological Rieske clusters that incorporates bis-benzimidazolate ligands ((Pr)bbim)(2-) has been developed ((Pr)bbimH(2) = 4,4-bis(benzimidazol-2-yl)heptane). The diferric and mixed-valence clusters have been prepared and characterized in both their protonated and deprotonated states. The thermochemistry of interconversions of these species has been measured, and the effect of protonation on the reduction potential is in good agreement to that observed in the biological systems. The mixed-valence and protonated congener [Fe(2)S(2)((Pr)bbim)((Pr)bbimH)](Et(4)N)(2) (4) reacts rapidly with TEMPO or p-benzoquinones to generate diferric and deprotonated [Fe(2)S(2)((Pr)bbim)(2)](Et(4)N)(2) (1) and 1 equiv of TEMPOH or 0.5 equiv of p-benzohydroquinones, respectively. The reaction with TEMPO is the first well-defined example of concerted proton-electron transfer (CPET) at a synthetic ferric/ferrous [Fe-S] cluster.
Topics: Benzimidazoles; Benzoquinones; Cyclic N-Oxides; Electron Spin Resonance Spectroscopy; Electron Transport; Iron Compounds; Iron-Sulfur Proteins; Ligands; Magnetic Resonance Spectroscopy; Models, Molecular; Protons
PubMed: 22519585
DOI: 10.1021/ja3019324 -
Journal of Molecular Graphics &... Nov 2016Placing electrical charges on nanomaterials is a means to extend their functional capabilities in nanoelectronics and sensoring applications. This paper explores the...
Placing electrical charges on nanomaterials is a means to extend their functional capabilities in nanoelectronics and sensoring applications. This paper explores the effect of charging nitrogen bases cytosine (Cyt) and adenine (Ade) via protonation on their noncovalent interaction with carbon nanotubes (CNT) using quantum chemical calculations performed at the M05-2X/6-31++G** level of theory alongside with a molecular graphics method. It is shown that the protonation of the bases causes threefold increase of the interaction energy in the CNT·Cyt·H and СNT·Ade·H complexes as compared to the CNT complexes formed with neutral bases. There is also some shortening of the base-CNT distance by ca 0.13Ǻ. The visualization of the electrostatic potential distribution with the molecular graphics reveals that the positive potential due to the protonated bases extends to a cylindrical domain of the nanotube segment adjacent to the base binding site. Furthermore, subtraction of the electrostatic potential maps of the protonated bases from the maps of their complexes with CNTs reveals an area of negative potential on the CNT surface, which reflects the location of the adsorbed base. The positive charge transfer of ca 0.3 e from the protonated bases to the CNT strengthens the interaction in the CNT·Cyt·H and СNT·Ade·H complexes. The analysis of the frontier orbitals shows that the LUMOs of the complexes mainly reside on the CNT, while the HOMOs spread over both components of each complex. The observed effects may facilitate the design of nanomaterials involving nitrogen bases and CNTs.
Topics: Adenine; Cytosine; Models, Molecular; Nanotubes, Carbon; Protons; Static Electricity; Thermodynamics
PubMed: 27684527
DOI: 10.1016/j.jmgm.2016.09.009 -
Chemistry (Weinheim An Der Bergstrasse,... Dec 2014The proton-induced electron-transfer reaction of a Cu(II) μ-thiolate complex to a Cu(I) -containing species has been investigated, both experimentally and...
The proton-induced electron-transfer reaction of a Cu(II) μ-thiolate complex to a Cu(I) -containing species has been investigated, both experimentally and computationally. The Cu(II) μ-thiolate complex [Cu(II) 2 (L(Me) S)2 ](2+) is isolated with the new pyridyl-containing ligand L(Me) SSL(Me) , which can form both Cu(II) thiolate and Cu(I) disulfide complexes, depending on the solvent. Both the Cu(II) and the Cu(I) complexes show reactivity upon addition of protons. The multivalent tetranuclear complex [Cu(I) 2 Cu(II) 2 (LS)2 (CH3 CN)6 ](4+) crystallizes after addition of two equivalents of strong acid to a solution containing the μ-thiolate complex [Cu(II) 2 (LS)2 ](2+) and is further analyzed in solution. This study shows that, upon addition of protons to the Cu(II) thiolate compound, the ligand dissociates from the copper centers, in contrast to an earlier report describing redox isomerization to a Cu(I) disulfide species that is protonated at the pyridyl moieties. Computational studies of the protonated Cu(II) μ-thiolate and Cu(I) disulfide species with LSSL show that already upon addition of two equivalents of protons, ligand dissociation forming [Cu(I) (CH3 CN)4 ](+) and protonated ligand is energetically favored over conversion to a protonated Cu(I) disulfide complex.
Topics: Copper; Crystallography, X-Ray; Disulfides; Electron Transport; Ligands; Molecular Structure; Organometallic Compounds; Protons; Solvents
PubMed: 25339345
DOI: 10.1002/chem.201403918