Investigation of substituent effect on O-C bond dissociation enthalpy of methoxy group in meta- and para-substituted anisoles.

This paper is focused on the theoretical investigation of O-C Bond Dissociation Enthalpy (BDE) of methoxy OCH3 group in 15 meta- and 15 para-substituted anisoles in gas phase, non-polar environment, and water. Density Functional Theory (DFT) calculations were carried out using M06-2X functional and 6-311++G(d,p) basis set. Obtained BDEs were correlated with Brown and Okamoto σp+ and Hammett σm constants representing commonly used descriptors of electron-donating or electron-withdrawing substituent effect. Obtained linear dependences allow the prediction of substituent effect on BDE using σp+ and σm constants. Calculated reaction enthalpies were also compared with available experimental and theoretical ab initio G4 values. Found results suggest that employed method may provide reliable thermochemistry data for demethylation of naturally occurring (poly)phenolic compounds, as well. In all studied environments, substituent induced changes in O-C BDE can be considered equal to those observed for the dissociation of phenolic O-H bond of substituted phenols.

Degradation Mechanisms of 4,7-Dihydroxycoumarin Derivatives in Advanced Oxidation Processes: Experimental and Kinetic DFT Study.

Coumarins represent a broad class of compounds with pronounced pharmacological properties and therapeutic potential. The pursuit of the commercialization of these compounds requires the establishment of controlled and highly efficient degradation processes, such as advanced oxidation processes (AOPs). Application of this methodology necessitates a comprehensive understanding of the degradation mechanisms of these compounds. For this reason, possible reaction routes between HO• and recently synthesized aminophenol 4,7-dihydroxycoumarin derivatives, as model systems, were examined using electron paramagnetic resonance (EPR) spectroscopy and a quantum mechanical approach (a QM-ORSA methodology) based on density functional theory (DFT). The EPR results indicated that all compounds had significantly reduced amounts of HO• radicals present in the reaction system under physiological conditions. The kinetic DFT study showed that all investigated compounds reacted with HO• via HAT/PCET and SPLET mechanisms. The estimated overall rate constants (koverall) correlated with the EPR results satisfactorily. Unlike HO• radicals, the newly formed radicals did not show (or showed negligible) activity towards biomolecule models representing biological targets. Inactivation of the formed radical species through the synergistic action of O2/NOx or the subsequent reaction with HO• was thermodynamically favored. The ecotoxicity assessment of the starting compounds and oxidation products, formed in multistage reactions with O2/NOx and HO•, indicated that the formed products showed lower acute and chronic toxicity effects on aquatic organisms than the starting compounds, which is a prerequisite for the application of AOPs procedures in the degradation of compounds.

Phenolic acids and their carboxylate anions: Thermodynamics of primary antioxidant action.

Phenolic acids represent naturally occurring antioxidants and play important role in free radicals scavenging. In this work, we have studied thermodynamics of the first step of primary antioxidant action for phenolic OH groups of benzoic and cinnamic acid derivatives, and their carboxylate anions. M06-2X/6-311++G(d,p) reaction enthalpies related to Hydrogen Atom Transfer (HAT), Single Electron Transfer - Proton Transfer (SET-PT), and Sequential Proton-Loss Electron-Transfer (SPLET) mechanisms were computed for model non-polar environment (benzene) and aqueous solution. The effect of acid structure on found reaction enthalpies was investigated, as well. For HAT, representing relevant reaction path in both environments, the lowest O-H bond dissociation enthalpies, BDE, were found for sinapic acid (347 kJ mol-1 in benzene and 337 kJ mol-1 in water). With two exceptions, carboxylate anions show lower BDEs than parent acids. In aqueous solution, enthalpies of the first step of SPLET from phenolic OH groups are low (135-199 kJ mol-1). It indicates thermodynamic feasibility of the mechanism for acids, as well as their carboxylate anions. Although enthalpies of electron transfer from dianions formed after successive deprotonations of carboxyl and phenolic groups in water are usually higher than BDEs, differences are within 25 kJ mol-1. Demethylation of OCH3 groups may affect radical scavenging activity of studied substances due to O-CH3 BDE considerably lower (230-269 kJ mol-1) in comparison to O-H ones.

Guaiacol oxidation: theoretical insight into thermochemistry of radical processes involving methoxy group demethylation.

Guaiacol (2-methoxyphenol) is naturally occurring phenolic compound essential in various research areas. Oxidative transformation of guaiacol can lead to the formation of various products, including 1,3-benzodioxole or ortho-quinone. Therefore, this study is focused on the investigation of the reaction enthalpies of experimentally observed guaiacol oxidation pathways in gas-phase, as well as in non-polar environment and aqueous solution. Corresponding Density Functional Theory (DFT) calculations were carried out using two hybrid functionals (M06-2X and B3LYP-D3). All reaction enthalpies, as well as Gibbs free energies, were also calculated using composite ab initio G4 method. M06-2X and G4 results show mutual agreement and the best accordance with available experimentally determined reaction enthalpies. Obtained Gibbs free reaction energies indicate that formation of ortho-quinone is thermodynamically preferred to formation of 1,3-benzodioxole at 298 K in studied environments. Moreover, all computational methods confirm that the reaction enthalpy of methoxy group demethylation, i.e. O-C bond dissociation enthalpy (BDE), is substantially lower in comparison to the enthalpy of hydrogen atom transfer from phenolic OH group. In the case of phenoxide anion of guaiacol, which can be formed in ionization supporting solvents, O-C BDE shows further significant decrease, exceeding 50 kJ mol-1, in comparison to parent molecule.HIGHLIGHTSReaction enthalpies and Gibbs free energies of individual steps of guaiacol transformation to 1,3-benzodioxole or ortho-quinone are studied in three environments.M06-2X functional and composite ab initio G4 methods provide reliable O-H and O-C bond dissociation enthalpies.Dissociation enthalpy of methoxy group O-C bond is lower by ca. 100 kJ mol-1 in comparison to phenolic O-H bond.Phenoxide anion of guaiacol shows substantially lower O-C BDE than parent molecule.

Antioxidant action of deprotonated flavonoids: Thermodynamics of sequential proton-loss electron-transfer.

Despite the intensive research on radical scavenging action of flavonoids, a systematic study of the thermochemistry for their mono-deprotonated species in aqueous solution is still missing. In this work, reaction enthalpies related to Sequential Proton-Loss Electron-Transfer (SPLET) mechanism were theoretically investigated for all mono-deprotonated forms of nine flavonoids: apigenin, luteolin, fisetin, kaempferol, quercetin, taxifolin, tricetin, tricin and cyanidin. Differences in reaction enthalpies of the first and the second deprotonation can be lower than 10 kJ mol-1, when two successive deprotonations occur in different aromatic rings of the molecule. For neutral flavonoids, thermodynamically preferred deprotonation sites are 4'-OH and 7-OH groups. In cyanidin (cation in native form), preferred second deprotonation site is 5-OH group. In the case of the formation of the preferred dianions, reaction enthalpies of the second proton loss are not affected by the structural distinctions between the flavonoids. In aqueous solution, deprotonated flavonoids show higher tendency to enter SPLET mechanism in comparison to Hydrogen Atom Transfer (HAT) or electron transfer.

From phenols to quinones: Thermodynamics of radical scavenging activity of para-substituted phenols.

Radical scavenging activity and subsequent oxidation resulting in quinone products represent one of the important features of phenols occurring in plants and other biological systems. However, corresponding thermochemistry data can be still considered scarce. For phenol and 25 para-substituted phenols, we investigate the thermodynamics of the individual reaction steps, including three subsequent hydrogen atom transfers, as well as hydroxyl HO radical addition, leading to final ortho-quinone formation. The substituent and solvent effect of water on corresponding reactions enthalpies is elucidated. Solvent enhances substituent induced changes in the investigated reaction enthalpies. The reliability of employed computational methods for the thermodynamics of hydrogen atom donating ability of studied phenols and catechols is assessed, too. Obtained linear equations enable estimation of studied reaction enthalpies from Hammett constants of substituents.

Thermodynamics of radical scavenging of symmetric carotenoids and their charged species.

For nine symmetric natural carotenoids, a comprehensive thermodynamics study of processes associated with their radical scavenging activity is proposed. We have investigated the hydrogen atom transfer (HAT) from the parent carotenoid, mono-radical species, radical cations and radical anions. Electron transfer and proton transfer reactions were also studied. Terminal units and carbon atoms in their vicinity were identified as thermodynamically favoured reaction sites of the HAT mechanism. Rhodoxanthin, canthaxanthin and astaxanthin, as strong antioxidants, without any pro-oxidative effect, were found to have bond dissociation enthalpies (BDE) higher than 300 kJ mol-1 and the most negative electron affinities. The electron transfer to a carotenoid is exothermic, while other studied reactions are endothermic. In solvent, the electron transfer reactions may be preferred instead of hydrogen atom transfer.

Theoretical study of the thermodynamics of the mechanisms underlying antiradical activity of cinnamic acid derivatives.

The role of antiradical moieties (catechol, guaiacyl and carboxyl group) and molecular conformation in antioxidative potency of dihydrocaffeic acid (DHCA) and dihydroferulic acid (DHFA) was investigated by density functional theory (DFT) method. The thermodynamic preference of different reaction paths of double (2H+/2e-) free radical scavenging mechanisms was estimated. Antiradical potency of DHCA and DHFA was compared with that exerted by their unsaturated analogs - caffeic acid (CA) and ferulic acid (FA). Cis/trans and anti-isomers of studied cinnamic acid derivatives may scavenge free radicals via double processes by involvement of catechol or guaiacyl moiety. Carboxyl group of syn-isomers may also participate in the inactivation of free radicals. Gibbs free energies of reactions with various free radicals indicate that syn-DHCA and syn-DHFA, colon catabolites that could be present in systemic circulation in low µM concentrations, have a potential to contribute to health benefits by direct free radical scavenging.

Pathological burst fracture in the cervical spine with negative red flags: a 12-year follow-up.

In 2004, a 61-year-old male presented to a chiropractic clinic complaining of neck pain after hearing a 'crunch' when getting out of bed that morning. The initial history intake and physical examination identified no red flags or indications for the patient's pain, with the exception of traction being pain-provoking. Conventional radiographs were ordered, which identified a pathological burst fracture of the fourth cervical vertebra. This Imaging Case Review (ICR) is to provide clinicians with a follow-up to the patient's care and current state.

En 2004, un homme de 61 ans se présente à une clinique de chiropratique en se plaignant de douleur cervicale après avoir entendu un craquement en se levant du lit le matin même. Au début, les antécédents et l'examen physique n'ont pas permis de déceler de signal d'alerte ou d'indication expliquant la douleur du patient, sauf pour la traction qui provoquait de la douleur. On a procédé à des radiographies traditionnelles qui ont décelé une fracture-éclatement pathologique de la quatrième vertèbre cervicale. Cet examen de cas d'imagerie a pour but de fournir aux cliniciens un suivi des soins prodigués au patient et de son état actuel.

Pathological burst fracture in the cervical spine with negative red flags: a case report.

OBJECTIVE: To report on a case of a pathological burst fracture in the cervical spine where typical core red flag tests failed to identify a significant lesion, and to remind chiropractors to be vigilant in the recognition of subtle signs and symptoms of disease processes. CLINICAL FEATURES: A 61-year-old man presented to a chiropractic clinic with neck pain that began earlier that morning. After a physical exam that was relatively unremarkable, imaging identified a burst fracture in the cervical spine. INTERVENTION & OUTCOMES: The patient was sent by ambulance to the hospital where he was diagnosed with multiple myeloma. No medical intervention was performed on the fracture. SUMMARY: The patient's initial physical examination was largely unremarkable, with an absence of clinical red flags. The screening tools were non-diagnostic. Pain with traction and the sudden onset of symptoms prompted further investigation with plain film imaging of the cervical spine. This identified a pathological burst fracture in the C4 vertebrae.

OBJECTIF: Présenter un cas de fracture-éclatement pathologique dans la colonne cervicale où les tests de base pour révéler des signes alarmants n'ont pas réussi à identifier une lésion significative, et rappeler les chiropraticiens à être vigilants dans la reconnaissance des signes et symptômes subtils des processus pathologiques. CARACTÉRISTIQUES CLINIQUES: Un homme âgé de 61 ans s'est présenté à une clinique de chiropratique avec une douleur cervicale qui a commencé tôt le matin. Après un examen physique relativement banal, l'imagerie a révélé une fracture-éclatement du rachis cervical. INTERVENTION ET RÉSULTATS: L'ambulance a transporté le patient à l'hôpital où il a reçu un diagnostic de myélome multiple. Aucune intervention médicale n'a été effectuée sur la fracture. RÉSUMÉ: L'examen physique initial du patient était banal et sans signes alarmants cliniques. Les outils de dépistage n'ont pas pu diagnostiquer. La douleur avec la traction et l'apparition soudaine de symptômes ont incité un examen plus approfondi avec l'imagerie par radiographie du rachis cervical. Cela a révélé une fracture-éclatement pathologique dans la vertèbre C4.

Acoustic assessment of speech privacy curtains in two nursing units.

Hospitals have complex soundscapes that create challenges to patient care. Extraneous noise and high reverberation rates impair speech intelligibility, which leads to raised voices. In an unintended spiral, the increasing noise may result in diminished speech privacy, as people speak loudly to be heard over the din. The products available to improve hospital soundscapes include construction materials that absorb sound (acoustic ceiling tiles, carpet, wall insulation) and reduce reverberation rates. Enhanced privacy curtains are now available and offer potential for a relatively simple way to improve speech privacy and speech intelligibility by absorbing sound at the hospital patient's bedside. Acoustic assessments were performed over 2 days on two nursing units with a similar design in the same hospital. One unit was built with the 1970s' standard hospital construction and the other was newly refurbished (2013) with sound-absorbing features. In addition, we determined the effect of an enhanced privacy curtain versus standard privacy curtains using acoustic measures of speech privacy and speech intelligibility indexes. Privacy curtains provided auditory protection for the patients. In general, that protection was increased by the use of enhanced privacy curtains. On an average, the enhanced curtain improved sound absorption from 20% to 30%; however, there was considerable variability, depending on the configuration of the rooms tested. Enhanced privacy curtains provide measureable improvement to the acoustics of patient rooms but cannot overcome larger acoustic design issues. To shorten reverberation time, additional absorption, and compact and more fragmented nursing unit floor plate shapes should be considered.

A theoretical study on the enthalpies of homolytic and heterolytic N-H bond cleavage in substituted melatonins in the gas-phase and aqueous solution.

In this paper, the study of melatonin and 60 meta- and ortho-substituted melatonins is presented. The reaction enthalpies related to the hydrogen atom transfer (HAT), single electron transfer - proton transfer (SET-PT) and sequential proton loss electron transfer (SPLET) have been calculated using DFT/B3LYP method in gas-phase and water. Results show that electron-withdrawing substituents increase the bond dissociation enthalpy (BDE), ionization potential (IP) and electron transfer enthalpy (ETE), while electron-donating ones cause a rise in the proton dissociation enthalpy (PDE) and proton affinity (PA). In ortho position, substituents show larger effect on reaction enthalpies than in meta position. In comparison to gas-phase, water attenuates the substituent effect on all reaction enthalpies. Results show that IP and BDE values can be successfully correlated with the indolic N-H bond length after electron abstraction, R(N-H(+*)), and the partial charge on the indolyl radical nitrogen atom, q(N). Furthermore, calculated IP and PA values for meta and ortho substituted melatonins show linear dependence on the energy of the highest occupied molecular orbital (E(HOMO)) of studied molecules in the two environments. SPLET represents the thermodynamically preferred mechanism in water.

On the radical scavenging activity of isoflavones: thermodynamics of O-H bond cleavage.

We have performed Density Functional Theory B3LYP/6-311++G** calculations of reaction enthalpies of antioxidant action mechanisms for nine isoflavones. O-H bond dissociation enthalpies, ionization potentials, proton dissociation enthalpies, proton affinities and electron transfer enthalpies related to Hydrogen Atom Transfer (HAT), Single Electron Transfer-Proton Transfer (SET-PT) and Sequential Proton-Loss Electron-Transfer (SPLET) mechanisms were investigated in gas- and solution-phases. Studies on the radical scavenging ability of isoflavones, contrary to various flavonoids, are still scarce. Thus, understanding of its thermodynamics can be considered beneficial. The selection of isoflavones (daidzein, formononetin, genistein, biochanin A, prunetin, 6-hydroxydaidzein, glycitein, orobol and santal) enables us to evaluate the effects of various structural features, such as the presence of methoxy (4'-OMe, 6-OMe, 7-OMe) and hydroxy (3'-OH, 5-OH, 6-OH) groups, on studied reaction enthalpies. The obtained results show that HAT can be attributed predominantly to the B ring, while SPLET takes place preferentially in the A ring, as was also indicated in experimental works.

Density functional theory (B3LYP) study of substituent effects on O-H bond dissociation enthalpies of trans-resveratrol derivatives and the role of intramolecular hydrogen bonds.

In this paper, 23 substituents with various electron-donating and electron-withdrawing characters were placed in available positions of trans-resveratrol in order to study their effect on the three O-H bond dissociation enthalpies (BDEs) via density functional theory (DFT) with Becke three-parameter exchange and Lee-Yang-Parr correlation (B3LYP). It has been found that the mutual positions of substituents and OH groups affect investigated BDEs substantially. Formation of strong intramolecular hydrogen bonds and suitable spin density distributions in several radicals result in low BDEs. Calculated BDEs have been correlated with Hammett constants, selected geometry parameters, and charge on phenoxy radical oxygen q(O). Found dependences are satisfactorily linear.

Theoretical study of structure, electronic properties, and photophysics of cyano-substituted thiophenes and terthiophenes.

In this paper, quantum chemical calculations for various cyano derivatives of thiophene and terthiophenes at the density functional theory (DFT) and ab initio Møller-Plesset (MP2) levels of theory are presented. In the case of the studied terthiophenes, CN groups located in the central part of the molecule lead to a preference of cis-cis geometry over trans-trans conformation. For alpha-substituted dicyano terthiophene, the investigation of torsional dependences shows that the highest energy barrier occurs at the perpendicular orientation of the aromatic rings. On the other hand, the dicyano substitution in the central part of terthiophene molecule exhibits the lowest energy barrier. Excitation energies were calculated using time-dependent density functional theory (TD-DFT). The obtained theoretical results show that the CN groups in alpha and beta positions have a distinct effect on the excitation energies and corresponding oscillator strengths. A CN group located in the alpha position causes a larger bathochromic shift than a CN group in the beta position. Besides, a CN group in the beta position has negligible influence on the position of the first absorption maximum.

DFT/B3LYP study of the substituent effect on the reaction enthalpies of the individual steps of single electron transfer-proton transfer and sequential proton loss electron transfer mechanisms of phenols antioxidant action.

The reaction enthalpies related to the individual steps of two phenolic antioxidants action mechanisms, single electron transfer-proton transfer (SET-PT) and sequential proton loss electron transfer (SPLET), for 30 meta and para-substituted phenols (ArOH) were calculated using DFT/B3LYP method. These mechanisms represent the alternative ways to the extensively studied hydrogen atom transfer (HAT) mechanism. Except the comparison of calculated reaction enthalpies with available experimental and/or theoretical values, obtained enthalpies were correlated with Hammett constants. We have found that electron-donating substituents induce the rise in the enthalpy of proton dissociation (PDE) from ArOH+* radical cation (second step in SET-PT) and in the proton affinities of phenoxide ions ArO- (reaction enthalpy of the first step in SPLET). Electron-withdrawing groups cause the increase in the reaction enthalpies of the processes where electron is abstracted, i.e., in the ionization potentials of ArOH (first step in SET-PT) and in the enthalpy of electron transfer from ArO- (second step in SPLET). Found results indicate that all dependences of reaction enthalpies on Hammett constants of the substituents are linear. The calculations of liquid-phase reaction enthalpies for several para-substituted phenols indicate that found trends hold also in water, although substituent effects are weaker. From the thermodynamic point of view, entering SPLET mechanism represents the most probable process in water.

Impulsive personality traits in male pedophiles versus healthy controls: is pedophilia an impulsive-aggressive disorder?

Pedophilia is characterized by sexual attraction to prepubescent children. Despite the extensive literature documenting the pervasive and pernicious effects of childhood sexual abuse, there is surprisingly little psychiatric literature on pedophilia and its etiology remains enigmatic. In recent years, the psychiatric literature on the phenomenology, neurobiology, and treatment of impulsive-aggressive disorders has grown significantly. As some investigators have conceptualized pedophilia as an impulsive-aggressive disorder, it is of interest whether recent advances in the study of impulsive-aggressive disorders might shed light on pathological mechanisms underlying pedophilia. In the following study, 20 male subjects with a DSM-IV diagnosis of pedophilia, heterosexual type were recruited from an outpatient facility for sexual offenders and compared to 24 demographically similar control subjects. Groups were compared on three personality instruments--the Millon Clinical Multiaxial Inventory-II (MCMI-II), the Temperament and Character Inventory (TCI), and the Dimensional Assessment of Personality Impairment-Questionnaire (DAPI-Q)--to assess for select impairment in impulsive-aggressive personality traits. Pedophiles showed severe and pervasive personality impairment relative to controls. Although there was evidence of impulsivity, the findings do not suggest a predominance of impulsive-aggressive traits, and in fact provide evidence of inhibition, passive-aggression, and harm avoidance. The notion of "compulsive-aggression" in pedophilia is proposed.