Theoretical Investigation of Iridium Complex with Aggregation-Induced Emission Properties.

The mechanism of aggregation-induced emission (AIE) for the bis(1-(2,4-difluorophenyl)-1H-pyrazole)(2-(20-hydroxyphenyl)-2-oxazoline)iridium(III) complex, denoted as Ir(dfppz)2(oz), was investigated with use DFT and the TD-DFT level of theory. The mechanism of radiationless deactivation of the triplet state was elucidated. Such a mechanism requires an additional, photophysical triplet channel of the internal conversion (IC) type, which is activated as a result of intramolecular motion deforming the structure of the oz ligand and distorting the iridium coordination sphere. Formally, the rotational movement of the oxazoline relative to the C-C bond in the oz ligand is the main active coordinate that leads to the opening of the triplet channel. The rotation of the oxazoline group and the elongation of the Ir-Nox bond cause a transition between the luminescent, low-lying triplet state with a d/π→π* characteristic (T1(eq)), and the radiationless d→d triplet state (T1(Ir)). This transition is made possible by the low energy barrier, which, based on calculations, was estimated at approximately 8.5 kcal/mol. Dimerization, or generally aggregation of the complex molecules, blocks the intramolecular movement in the ligand and is responsible for a strong increase in the energy barrier for the T1(eq)⇝T1(Ir) conversion of triplet states. Thus, the aggregation phenomenon blocks the nonradiative deactivation channel of the excited states and, consequently, contributes to directing the photophysical process toward phosphorescence. The mechanism involved in locking the nonradiative triplet path can be called restricted access to singlet-triplet crossing (RASTC).

Health Behaviors and Health-Related Quality of Life in Female Medical Staff.

The aim of this study was to evaluate the relationship between the intensity of health behaviors and health-related quality of life in female mid-level medical staff. The study group consisted of 153 female mid-level medical staff members. The intensity of health behaviors was examined with the Polish version of Health Behavior Inventory. Health-related quality of life was verified with the Short Form Health Survey questionnaire (SF 36v2). Among the participants, 33% had low, 39% average, and 28% high intensity of health behaviors. The mental component of health-related quality of life was rated higher (83.3 ± 15.3 points) compared to the physical one. The lowest health-related quality of life was observed in the domain of "bodily pain", while the highest was found for the domain of "social functioning". Both the physical and mental components of health-related quality of life were significantly positively correlated with health behavior prevalence in all its categories. The post-hoc tests revealed the variation in physical and mental components of HRQoL according to the level of health behavior intensity.

Mechanical Modulation of the Solid-State Luminescence of Tricarbonyl Rhenium(I) Complexes through the Interplay between Two Triplet Excited States.

Mechanoresponsive luminescence (MRL) materials promise smart devices for sensing, optoelectronics and security. We present here the first report on the MRL activity of two ReI complexes, opening up new opportunities for applications in these fields. Both complexes exhibit marked solid-state luminescence enhancement (SLE). Furthermore, the pristine microcrystalline powders emit in the yellow-green region, and grinding led to an amorphous phase with concomitant emission redshift and shrinking of the photoluminescence (PL) quantum yields and lifetimes. Quantum chemical calculations revealed the existence of two low-lying triplet excited states with very similar energy levels, that is, 3 IL and 3 MLCT, having, respectively, almost pure intraligand (IL) and metal-to-ligand charge-transfer (MLCT) character. Transition between these states could be promoted by rotation around the pyridyltriazole-phenylbenzoxazole bond. In the microcrystals, in which rotations are hindered, the 3 IL state induces the prominent PL emission at short wavelengths. Upon grinding, rotation is facilitated and the transition to the 3 MLCT state results in a larger proportion of long-wavelength PL. FTIR and variable-temperature PL spectroscopy showed that the opening of the vibrational modes favours non-radiative deactivation of the triplet states in the amorphous phase. In solution, PL only arises from the 3 MLCT state. The same mechanism accounts for the spectroscopic differences observed when passing from crystals to amorphous powders, and then to solutions, thereby clarifying the link between SLE and MRL for these complexes.

Structure and electronic spectra of neutral and protonated forms of anticonvulsant drug lamotrigine.

In this work, the geometry, acid-base properties, pKa, electronic spectra, and fluorescence spectrum of anticonvulsant drug lamotrigine (LTG) are investigated with the DFT/TD-DFT method and PCM solvent model. Calculated transition with the B3LYP functional at 295 nm corresponds to experimental absorption transition at 306 nm in water. In acidic conditions, the computed maximum transition occurs at 249 nm, comparing with experimental one at 270 nm. The dependence of calculated transitions on density functional used and different solvents in PCM model was studied. The computed transition of fluorescence is at 435 nm, while experimental occurs at 370 nm. Maps of electrostatic potential (MEPs) for S0 and S1 reveal that the ground state of LTG is more polar than the first excited state. Structurally, in the excited state of LTG, the triazine ring is noticeably distorted. Graphical Abstract Molecular elecrostatic potentials for S0 and S1 states of the lamotrigine molecule.

Association Between Objectively Measured Physical Activity And Musculoskeletal Disorders, And Perceived Work Ability Among Adult, Middle-Aged And Older Women.

PURPOSE: The purpose of this study was to assess the relationship between objectively measured physical activity and perceived work ability and musculoskeletal disorders among adult, middle-aged, and older women. PATIENTS AND METHODS: This study used a cross-sectional design with a convenience sample of 348 women divided into 3 age groups: 30-49 years (n=111), 50-65 years (n=120), 66-75 years (n=117). Weekly physical activity was monitored using tri-axial accelerometer ActiGraph Gt3X. Perceived work ability was assessed using the standardized Work Ability Index (WAI) questionnaire. Information about the occurrence and intensity of musculoskeletal disorders was collected using standardized Nordic Musculoskeletal Questionnaire (NMQ) expanded by visual analog pain intensity scale (VAS). RESULTS: Regardless of age, women who met physical activity recommendations achieved higher scores in each part of the WAI, and also in the total WAI scores. However, the most significant differences were found in women aged 50-64 years, and included the following items: subjective work ability, work ability in relation to demands, work impairments, sick leave in the past year. Total WAI scores were also significantly higher in women aged 30-49 and 50-64 years who met PA recommendations in comparison to women who did not meet recommendations. Also, significant relations between the frequency of occurrence of musculoskeletal problems and meeting physical activity recommendations were found in women aged 50-64 years. Those who were more physically active reported less musculoskeletal problems in shoulders (p=0.006) and ankles/feet (p=0.018) regions. CONCLUSION: Adherence to Global Recommendations on Physical Activity for Health disseminated by WHO is related to better-perceived work ability among adult (30-49 years) and middle-aged (50-64 years) women. There is also a relationship between adherence to recommendations of physical activity and frequency and intensity of musculoskeletal pain among middle-aged women.

Mechanism of the photo-induced activation of CoC bond in methylcobalamin-dependent methionine synthase.

Methylcobalamin (MeCbl)-dependent enzyme methionine synthase (MetH), plays a critical role in the catalysis of methyl group transfer from methyltetrahydrofolate (CH3-H4folate) to homocysteine. It often performs a side reaction to generate cob(II)alamin through photolysis of the organometallic CoC σ bond. A hybrid QM/MM method has been applied to explore the photochemistry of MeCbl-bound MetH. The photolytic properties of MeCbl inside MetH are mediated by its manifold of low-lying excited states. The corresponding potential energy surfaces (PESs) of the electronically excited S1 state has been constructed as a function of axial bond lengths to elucidate the mechanism of photo-induced activation of CoC bond inside the enzyme. The analysis of the S1 PES has revealed that the two different electronic states of the S1 PES, namely metal-to-ligand charge transfer (MLCT) and the ligand field (LF), are relevant to the photodissociation of the CoC bond. There are two possible pathways identified, Path A and Path B, that connect the MLCT to LF state that represent possible photodissociation mechanisms. In the case of MetH, one possible photodissociation pathway (Path B) was identified based on the energetics of the MLCT and LF states. The energetically accessible Path B involves the initial detachment of the Co-NIm bond followed by a subsequent displacement of the CoC bond prior to the formation of cob(II)alamin / CH3 radical pair (RP). The photochemical data of base-on MeCbl in solution was compared with the computed result of MeCbl-bound MetH to understand the effect of the enzymatic environment on the photolytic properties of MeCbl.

Off to the Races: Comparison of Excited State Dynamics in Vitamin B12 Derivatives Hydroxocobalamin and Aquocobalamin.

Ultrafast time-resolved spectroscopy was used to study the photochemistry of hydroxocobalamin (HOCbl) and aquocobalamin (H2OCbl+) in solution. Spectroscopic measurements and TD-DFT simulations provide a consistent picture of the spectroscopy and photochemistry. Excitation of H2OCbl+ results in formation of an excited state followed by rapid internal conversion to the ground state (0.35 ± 0.15 ps) through an S1/S0 seam at a slightly elongated Co-O bond length and a significantly elongated Co-NIm bond length. In contrast, the initial elongation of the axial bonds in HOCbl is followed by contraction to an excited state minimum with bonds slightly shorter than those in the ground state. Internal conversion to the ground state follows on a picosecond time scale (5.3 ± 0.4 ps). For both compounds, photodissociation forming cob(II)alamin and hydroxyl radicals (∼1.5% yield) requires excitation to highly excited states. Dissociation is mediated by competition between internal conversion to the S1 surface and prompt bond cleavage.

Photolytic Properties of Antivitamins B12.

Antivitamins B12 represent an important class of vitamin B12 analogues that have gained recent interest in several research areas. In particular, 4-ethylphenylcobalamin (EtPhCbl) and phenylethynylcobalamin (PhEtyCbl) exemplify two such antivitamins B12 which have been characterized structurally and chemically. From a spectroscopic point of view, EtPhCbl is photolabile with a very low quantum yield of photoproducts, while PhEtyCbl is incredibly photostable. Herein, DFT and TD-DFT computations are provided to explore the photolytic properties of these compounds to shed light on the electronic properties that are indicative of these differences. Potential energy surfaces (PESs) were constructed to investigate the mechanisms of photodissociation leading to radical pair (RP) formation and the mechanisms of deactivation to the ground state. The S1 PESs for each antimetabolite contain two energy minima, one being the metal-to-ligand charge transfer (MLCT) and another the ligand-field (LF) state. There are two possible pathways for photodissociation that can be identified for EtPhCbl but only one (path B) is energetically feasible and involves the lengthening of the Co-NIm bond through the MLCT region followed by the lengthening of the Co-C bond through the LF region. For PhEtyCbl, there is not an energetically favorable path for photolysis; rather, internal conversion (IC) is the significantly preferred photophysical event.

Photodissociation of ethylphenylcobalamin antivitamin B12.

Biologically active forms of cobalamins are crucial cofactors in biochemical reactions and these metabolites can be inhibited by their structurally similar analogues known as antivitamins B12. Phenylethynylcobalamin (PhEtyCbl) or 4-ethylphenylcobalamin (EtPhCbl) exemplify recently synthesized and structurally characterized antivitamins B12. Herein, DFT and TD-DFT studies of EtPhCbl are provided to explore its photochemical behavior, which may lead to design of arylcobalamins that can be used as therapeutic agents in light activated drug applications. To understand the photolability of EtPhCbl, a potential energy surface (PES) for the photodissociation of the Co-C bond was constructed. The S1 PES contains two energy minima, one being metal-to-ligand charge transfer (MLCT) and another the ligand-field (LF) state. There are two possible pathways for photodissociation: the first pathway (path A) involves initially lengthening the Co-C bond from the MLCT minimum and then elongation of Co-NIm while the second pathway (path B) involves the lengthening of the Co-NIm bond through the MLCT region followed by the lengthening of the Co-C bond through the LF region. It is shown that photodissociation involving path A is not energetically favorable whereas preferable photodissociation of the Co-C bond involves path B.

Mechanism of Co-C photodissociation in adenosylcobalamin.

A mechanism of Co-C bond photodissociation in the base-on form of adenosylcobalamin (AdoCbl) was investigated by time-dependent density functional theory (TD-DFT). The key mechanistic step involves singlet radical pair (RP) generation from the first electronically excited state (S1). To connect TD-DFT calculations with ultra-fast excited state dynamics, the potential energy surface (PES) of the S1 state was constructed using Co-C and Co-NIm axial coordinates. The S1 PES can be characterized by two minima separated by a seam resulting from the crossing of two surfaces, of metal-to-ligand charge transfer (MLCT) character near the minimum, and a shallow ligand field (LF) surface at elongated axial bond distances. Only one possible pathway for photolysis (path A) was identified based on energetic grounds. This pathway is characterized by the first elongation of the Co-C bond, followed by photolysis from an LF state where the axial base is partially detached. A new perspective on the photolysis of AdoCbl is then gained by connecting TD-DFT results with available experimental observations.

The role of spin-orbit coupling in the photolysis of methylcobalamin.

The photolysis of the methylcobalamin cofactor (MeCbl) in its base-off form was investigated by considering the extent of spin-orbit coupling (SOC). Triplet Co-C photodissociation pathways previously invoked at the density functional theory level using Landau-Zener theory were further validated with ab initio calculations that combine SOC based on multi-state second order perturbation theory. It was determined that SOC is feasible between singlet and triplet states at elongated Co-C distances, leading to photodissociation from the state having dominant σ(dz(2)) character, by either direct coupling with the lowest singlet states or by crossing with SOC mixed triplets.

Photolytic properties of cobalamins: a theoretical perspective.

This Perspective Article highlights recent theoretical developments, and summarizes the current understanding of the photolytic properties of cobalamins from a computational point of view. The primary focus is on two alkyl cobalamins, methylcobalamin (MeCbl) and adenosylcobalamin (AdoCbl), as well as two non-alkyl cobalamins, cyanocobalamin (CNCbl) and hydroxocobalamin (HOCbl). Photolysis of alkyl cobalamins involves low-lying singlet excited states where photodissociation of the Co-C bond leads to formation of singlet-born alkyl/cob(ii)alamin radical pairs (RPs). Potential energy surfaces (PESs) associated with cobalamin low-lying excited states as functions of both axial bonds, provide the most reliable tool for initial analysis of their photochemical and photophysical properties. Due to the complexity, and size limitations associated with the cobalamins, the primary method for calculating ground state properties is density functional theory (DFT), while time-dependent DFT (TD-DFT) is used for electronically excited states. For alkyl cobalamins, energy pathways on the lowest singlet surface, connecting metal-to-ligand charge transfer (MLCT) and ligand field (LF) minima, can be associated with photo-homolysis of the Co-C bond observed experimentally. Additionally, energy pathways between minima and seams associated with crossing of S1/S0 surfaces, are the most efficient for internal conversion (IC) to the ground state. Depending on the specific cobalamin, such IC may involve simultaneous elongation of both axial bonds (CNCbl), or detachment of axial base followed by corrin ring distortion (MeCbl). The possibility of intersystem crossing, and the formation of triplet RPs is also discussed based on Landau-Zener theory.

Electronically excited states of cob(ii)alamin: insights from CASSCF/XMCQDPT2 and TD-DFT calculations.

The low-lying excited states of cob(ii)alamin were investigated using time-dependent density functional theory (TD-DFT). The performance of TD-DFT calculations was further evaluated using CASSCF/XMCQDPT2, where both four-coordinate and five-coordinate models of cob(ii)alamin were considered. Dependence of electronic structure on the axial base was then investigated using TD-DFT. Consistent with previous benchmarks, the BP86 functional provides a reliable description of the electronically excited states. It was found that the dyz + π → dz(2) character of the D1 state increases with respect to the axial base distance, corresponding to a lowering in energy of anti-bonding dz(2) orbitals, leading to near a degeneracy between the ground, and D1 states in the base-off form.

Photostability of Hydroxocobalamin: Ultrafast Excited State Dynamics and Computational Studies.

Hydroxocobalamin is a potential biocompatible source of photogenerated hydroxyl radicals localized in time and space. The photogeneration of hydroxyl radicals is studied using time-resolved spectroscopy and theoretical simulations. Radicals are only generated for wavelengths <350 nm through a mechanism that involves competition between prompt dissociation and internal conversion. Characterization of the lowest-lying singlet potential energy surface provides insight into the photochemistry of hydroxocobalamin and other cobalamin compounds.

Mechanism of Co-C bond photolysis in methylcobalamin: influence of axial base.

A mechanism of Co-C bond photolysis in the base-off form of the methylcobalamin cofactor (MeCbl) and the influence of its axial base on Co-C bond photodissociation has been investigated by time-dependent density functional theory (TD-DFT). At low pH, the MeCbl cofactor adopts the base-off form in which the axial nitrogenous ligand is replaced by a water molecule. Ultrafast excited-state dynamics and photolysis studies have revealed that a new channel for rapid nonradiative decay in base-off MeCbl is opened, which competes with bond dissociation. To explain these experimental findings, the corresponding potential energy surface of the S1 state was constructed as a function of Co-C and Co-O bond distances, and the manifold of low-lying triplets was plotted as a function of Co-C bond length. In contrast to the base-on form of MeCbl in which two possible photodissociation pathways were identified on the basis of whether the Co-C bond (path A) or axial Co-N bond (path B) elongates first, only path B is active in base-off MeCbl. Specifically, path A is inactive because the energy barrier associated with direct dissociation of the methyl ligand is higher than the barrier of intersection between two different electronic states: a metal-to-ligand charge transfer state (MLCT), and a ligand field state (LF) along the Co-O coordinate of the S1 PES. Path B initially involves displacement of the water molecule, followed by the formation of an LF-type intermediate, which possesses a very shallow energy minimum with respect to the Co-C coordinate. This LF-type intermediate on path B may result in either S1/S0 internal conversion or singlet radical pair generation. In addition, intersystem crossing (ISC) resulting in generation of a triplet radical pair is also feasible.

Mechanism of Co-C bond photolysis in the base-on form of methylcobalamin.

A mechanism of Co-C bond photodissociation in the base-on form of the methylcobalamin cofactor (MeCbl) has been investigated employing time-dependent density functional theory (TD-DFT), in which the key step involves singlet radical pair generation from the first electronically excited state (S1). The corresponding potential energy surface of the S1 state was constructed as a function of Co-C and Co-Naxial bond distances, and two possible photodissociation pathways were identified on the basis of energetic grounds. These pathways are distinguished by whether the Co-C bond (path A) or Co-Naxial bond (path B) elongates first. Although the final intermediate of both pathways is the same (namely a ligand field (LF) state responsible for Co-C dissociation), the reaction coordinates associated with paths A and B are different. The photolysis of MeCbl is wavelength-dependent, and present TD-DFT analysis indicates that excitation in the visible α/ß band (520 nm) can be associated with path A, whereas excitation in the near-UV region (400 nm) is associated with path B. The possibility of intersystem crossing, and internal conversion to the ground state along path B are also discussed. The mechanism proposed in this study reconciles existing experimental data with previous theoretical calculations addressing the possible involvement of a repulsive triplet state.

[Physical recreational activity and musculoskeletal disorders in nurses]. / Rekreacyjna aktywnosc fizyczna i dolegliwosci miesniowo-szkieletowe pielegniarek.

BACKGROUND: The role of physical activity (PA) in the prevention and treatment of civilization diseases has been recognized by the medical society. Despite extensive knowledge and well-documented evidence of health aspects of PA, the identification and assessment of the PA level in various social and professional groups are still needed. The main goal of this research was to work out a preliminary assessment of possible relationship between recreational physical activity and reduced common musculoskeletal disorders in nurses. MATERIAL AND METHODS: The study included 93 nurses, aged 41.4+/-7.31, with body height of 164.4+/-7.04 and body weight of 64.5+/-10.8. The Nordic Musculoskeletal Questionnaire (NMQ) was applied to assess pain and the International Physical Activity Questionnaire (IPAQ) (long version) to assess the level of physical activity. The intergroup differences, due to the occurrence of pain and physical activity levels, were determined using the Mann Whitney test and the Kruskal Wallis test. To evaluate the significance of individual factors potentially influencing the onset of musculoskeletal pains, the Chi2 test for independence was performed. RESULTS: Over 70% of the examined nurses reported musculoskeletal complaints, mostly related with lower back pain. Taking up recreational activity, of at least moderate to vigorous physical activity (MVPA), reduces the risk of musculoskeletal disorders. CONCLUSION: It is most likely that recreational physical activity at appropriate parameters may prevent musculoskeletal disorders, especially in nurses with long work experience. However, this hypothesis needs to be verified by experimental studies with use of objective tools for the assessment of physical activity.

Mechanism of the S1 excited state internal conversion in vitamin B12.

To explain the photostability of vitamin B12, internal conversion of the S1 state was investigated using TD-DFT. The active coordinates for radiationless deactivation were determined to be elongated axial bonds, overcoming a 5.0 kcal mol(-1) energy barrier between the relaxed ligand-to-metal charge transfer (S1), and the ground (S0) states.

[The incidence of hypothyroidism symptoms and risk factors for cardiovascular events in subclinical hypothyroidism]. / Czestosc wystepowania objawów niedoczynnosci tarczycy oraz czynników ryzyka sercowo-naczyniowego w subklinicznej niedoczynnosci tarczycy.

UNLABELLED: The clinical significance of subclinical hypothyroidism (SH) has not been determined. There are different opinions with regard to symptoms and clinical consequences of SH as well as effectiveness of treatment. Aim of study was the analysis of incidence of hypothyroidism symptoms and selected cardiovascular risk factors in patients with SH in comparison to euthyroid individuals and the evaluation of the effect of treatment of SH on the above parameters. MATERIALS AND METHODS: Fifty patients were included in the study: 25 with SH, 25 in euthyreosis (C). The incidence of hypothyroidism symptoms and metabolic syndrome (MS), as well as total cholesterol (TCH), LDL, HDL triglycerides (TGL), glucose levels, values of systolic (SBP) and diastolic (DBP) blood pressure and the relationship between these factors and laboratory indexes of SH intensity were analyzed. Moreover, the risk of cardiovascular mortality (RCM) with the application of the HeartSCORE Risk Chart was evaluated. After a period of six months a similar analysis in the SH group was conducted; all the patients were administered L-thyroxin (mean dose +/- SD: 67.5 +/- 32.1 microg). RESULTS: The mean number of hypothyroidism symptoms was higher in SH than in C group (SH: 8.4 +/- 3.2 vs. C: 1.7 +/- 1.5, p < 0.0005). Normalization of TSH observed in 17 patients resulted in a decrease in the mean number of symptoms (9.1 +/- 2.8 vs. 5.9 +/- 2.9, p < 0.0001). There were not differences between groups in the incidence of the MS and MS components and also the RCM. However only in SH group a positive correlations between TSH and BMI, TSH and age, age and TCH and LDL levels and SBP DBP values and also between TSH and the RCM were noted. Normalization of TSH level resulted in a decrease in the RCM (p = 0.055). CONCLUSIONS: Treatment of SH might bring potential benefits; it might lessen symptoms and reduce the risk of cardiovascular mortality.

Redox potentials and protonation of the A-cluster from acetyl-CoA synthase. A density functional theory study.

Density functional theory (DFT/BP86) and the polarized continuum model (PCM/ε = 20) have been applied to perform calculations for the A-cluster of acetyl-CoA synthase enzyme. The geometry optimization was carried out for the oxidized, one- and two-electron reduced A-cluster as well as for A-cluster with ligands important in the catalytic cycle, i.e., H2O, CO, CH3, OH(-), and H(+). The electronic structure of the studied species (spin densities and NBO charges) was analyzed and the metal-metal interactions were investigated with the use of Wiberg bond indices (WBIs). The pKa values and the reduction potentials have been determined. On the basis of the calculations, the mechanism of PCET reductive activation of the A-cluster has been proposed for the methylation catalytic step.