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We examined the static and dynamic characters of the red luminescence in the protein-Au(III) compounds, directly comparing multiple proteins: BSA, OVA, trypsin, and insulin. These four protein-Au(III) complexes showed a nearly identical excitation-emission pattern, not only the wavelength of luminescence (λem ∼ 640 nm). Lifetimes of the red luminescence shared a common value of ∼300 ns. Kinetics of the luminophore formation was consistently described by a Langmuir-type chemisorption of Au(III) for these proteins, coinciding with the protein conformation change at pH ∼ 10. These observations and the protein structural analyses support that the red luminophore formation involves Au(III) coordination to a common motif within these proteins.

Groundwater is one of the major resources to supply the agriculture and urban water demand. Vulnerability of groundwater resources due to chemical substances is a crucial concern for groundwater quality management. The different nitrogen compounds, especially nitrate, plays an important role in groundwater quality. In last two decades, the efficient approaches called soft computing (SC) models were used for assessing the groundwater pollution. This study aims to assess the applications of various SC models for simulating the groundwater pollution due to nitrate contamination. In this way, the past trends and current applications of those models and essential factors required for assessing the ground water quality are demonstrated. Ultimately, several research gaps and possible future research direction are proposed.

Sutures are essential to approximate tissues and enable healing by first intention until a wound regains its original tensile strength. The mechanical properties of sutures are well documented, but the effects of exposing sutures to skin preparation solutions used in surgery are not. This study was performed to investigate whether 2% chlorhexidine and 70% isopropyl alcohol skin preparation, commonly used prior to incision and prior to closure, has any effect on the mechanical properties of several commonly used surgical suture types. Four suture types were soaked in either 2% chlorhexidine and 70% isopropyl alcohol or Hartmann's solution for 5 minutes. All sutures were left to dry for 11 days before being tested to failure using an Instron 3367 tensile testing machine. Testing revealed significant differences in failure load, ultimate tensile stress, and Young's modulus between suture types (P

Monomeric organolithium (LiR) complexes could provide enhanced Li–C bond reactivity and suggest mechanisms for a plethora of LiR-mediated reactions. They are highly sought-after but remain a synthetic challenge for organometallic chemists. In this work, we report the synthesis and characterisation of a monomeric (trimethylsilyl)methyl lithium complex, namely [Li(CH2SiMe3)(κ3-N,N’,N”-Me6Tren)] (1), where Me6Tren is a tetradentate neutral amine ligand. The structure of 1 was comprehensively examined by single-crystal X-ray diffraction, variable temperature NMR spectroscopy and electron absorption spectrum. Complex 1 decomposes via ligand C–H and C–N activations to produce a Li amide complex 2. Preliminary reactivity studies of 1 reveal C=O insertion and C–H activation reaction patterns.

A small series of boranil complexes has been studied by fluorescence spectroscopy. Weakly fluorescent in most organic solvents at room temperature, the target compounds display bright emission in the crystalline phase. X-ray diffraction patterns obtained for single crystals indicate a distorted tetrahedral geometry around the O-B-N center with the boron atom being displaced from the plane of the heterobicyclic ring. Consideration of the various bond lengths in comparison with those of reference compounds indicates that the ancillary phenyl ring, bearing different para-substituents, does not make a prominent contribution to the molecular dipole moment in the solid state. Absorption and fluorescence spectra recorded for the crystals remain remarkably similar to those for liquid solutions and display large Stokes shifts. Proximity broadening is observed in one case. The nitrophenyl derivative exhibits additional absorption and emission bands unique to the solid state and could be indicative of an intermolecular charge-transfer transition. The optical properties are discussed in terms of the crystal packing diagrams.

The active vitamin D compound, 1,25-dihydroxyvitamin D3 (1,25D) is produced in skin cells following exposure to ultraviolet radiation (UV) from the sun. However, there are many harmful effects of UV which include DNA damage caused by direct absorption of UV, as well as that caused indirectly via UV-induced reactive oxygen species (ROS). Interestingly, 1,25D and analogs have been shown to reduce both direct and indirect UV-induced DNA damage in skin cells. This was accompanied by reductions in ROS and in nitric oxide products with 1,25D following UV. Moreover, following acute UV exposure, 1,25D has been demonstrated to increase p53 levels in skin, which would presumably allow for repair of cells with damaged DNA, or apoptosis of cells with irreparably damaged DNA. Previous studies have also shown that p53 reduces intracellular ROS. Furthermore, 1,25D has been shown to induce metallothioneins, which are potent free radical scavengers. In addition to these protective effects, 1,25D has been demonstrated to inhibit stress-activated c-Jun N-terminal kinases following UV exposure, and to increase levels of the stress-induced protein heme oxygenase-1 in a model of oxidative stress. Herein, we discuss the protective effects of 1,25D and analogs in the context of UV, oxidative stress and skin cancer.

The activation mechanism of the ErbB family of receptors is of considerable medical interest as they are linked to a number of human cancers, including an aggressive form of breast cancer. In the rat analogue of the human ErbB2 receptor, referred to as Neu, a point mutation in the transmembrane domain (V664E) has been shown to trigger oncogenic transformation. While the structural impact of this mutation has been widely studied in the past to yield models for the active state of the Neu receptor, little is known about the impact of cholesterol on its structure. Given previous reports of the influence of cholesterol on other receptor tyrosine kinases (RTKs), as well as the modulation of lipid composition in cancer cells, we wished to investigate how cholesterol content impacts the structure of the Neu transmembrane domain. We utilized high-resolution magic angle spinning solid-state NMR to measure 13C–13C coupling of selectively labelled probe residues in the Neu transmembrane domain in lipid bilayers containing cholesterol. We observe inter-helical coupling between residues that support helix–helix interactions on both dimerization motifs reported in the literature (A661-XXX-G665 and I659-XXX-V663). We further explore how changes in cholesterol concentration alter transmembrane domain interactions and the properties and mechanics of the bilayer. We interpret our results in light of previous studies relating RTK activity to cholesterol enrichment and/or depletion, and propose a novel model to explain our data that includes the recognition and binding of cholesterol by the Neu transmembrane domain through a putative cholesterol-recognition/interaction amino acid consensus sequence.\ud \ud

We revisit the prevailing hypothesis that the red fluorophore (λem = 640 nm) in the bovine serum albumin (BSA)–gold (Au) compound is a Au25 nanocluster. To examine the hypothesis, we investigated t...

Antibiotic resistance is a significant threat to human health, with natural products remaining the best source for new antimicrobial compounds. Antimicrobial peptides (AMPs) are natural products with great potential for clinical use as they are small, amenable to customization, and show broad‐spectrum activities. Lynronne‐1 is a promising AMP identified in the rumen microbiome that shows broad‐spectrum activity against pathogens such as methicillin‐resistant Staphylococcus aureus and Acinetobacter baumannii. Here we investigated the structure of Lynronne‐1 using solution NMR spectroscopy and identified a 13‐residue amphipathic helix containing all six cationic residues. We used biophysical approaches to observe folding, membrane partitioning and membrane lysis selective to the presence of anionic lipids. We translated our understanding of Lynronne‐1 structure to design peptides which varied in the size of their hydrophobic helical face. These peptides displayed the predicted continuum of membrane‐lysis activities in vitro and in vivo, and yielded a new AMP with 4‐fold improved activity against A. baumannii and 32‐fold improved activity against S. aureus., Here we describe the biophysical characterization of Lynronne‐1, an antimicrobial peptide found in the bovine rumen microbiome. We reveal the location of an amphipathic helix containing all six cationic residues, and observe lipid‐selective folding, membrane‐binding and lysis. Our structural data were used to design three variants with changes in the size of the hydrophobic helical face, one of which yielded 32‐fold improved activity in vivo.

The vitamin D hormone, 1,25dihydroxyvitamin D3 (1,25(OH)2D3), and related compounds derived from vitamin D3 or lumisterol as a result of metabolism via the enzyme CYP11A1, have been shown, when applied 24 hours before or immediately after UV irradiation, to protect human skin cells and skin from DNA damage due to UV exposure, by reducing both cyclobutane pyrimidine dimers (CPD) and oxidative damage in the form of 8‐oxo‐7,8‐dihydro‐2′‐deoxyguanosine (8‐OHdG). We now report that knockdown of either the vitamin D receptor or the endoplasmic reticulum protein ERp57 by small, interfering RNA (siRNA) abolished the reductions in UV‐induced DNA damage with 20‐hydroxyvitamin D3 or 24‐hydroxylumisterol3, as previously shown for 1,25(OH)2D3. Treatment with 1,25(OH)2D3 reduced oxygen consumption rates in UV‐exposed and sham‐exposed human keratinocytes and reduced phosphorylation of cyclic AMP response binding element protein (CREB). Both these actions have been shown to inhibit skin carcinogenesis after chronic UV exposure, consistent with the anticarcinogenic activity of 1,25(OH)2D3. The requirement for a vitamin D receptor for the photoprotective actions of 1,25(OH)2D3 and of naturally occurring CYP11A1‐derived vitamin D–related compounds may explain why mice lacking the vitamin D receptor in skin are more susceptible to UV‐induced skin cancers, whereas mice lacking the 1α‐hydroxylase and thus unable to make 1,25(OH)2D3 are not more susceptible. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

The reticulon family of integral membrane proteins are conserved across all eukaryotes and typically localize to the endoplasmic reticulum (ER), where they are involved in generating highly-curved tubules. We recently demonstrated that Reticulon-like protein B13 (RTNLB13) from Arabidopsis thaliana contains a curvature-responsive amphipathic helix (APH) important for the proteins’ ability to induce curvature in the ER membrane, but incapable of generating curvature by itself. We suggested it acts as a feedback element, only folding/binding once a sufficient degree of curvature has been achieved, and stabilizes curvature without disrupting the bilayer. However, it remains unclear whether this is unique to RTNLB13 or is conserved across all reticulons—to date, experimental evidence has only been reported for two reticulons. Here we used biophysical methods to characterize a minimal library of putative APH peptides from across the 21 A. thaliana isoforms. We found that reticulons with the closest evolutionary relationship to RTNLB13 contain curvature-sensing APHs in the same location with sequence conservation. Our data reveal that a more distantly-related branch of reticulons developed a ~ 20-residue linker between the transmembrane domain and APH. This may facilitate functional flexibility as previous studies have linked these isoforms not only to ER remodeling but other cellular activities.

International audience; The understanding of photoinduced ligand exchange mechanisms in polypyridyl ruthenium(II) complexes operating in aqueous solution is of crucial importance to rationalize their photoreactivity. Herein, we demonstrate that a synergetic use of ab initio molecular dynamics simulations and static calculations, both conducted at the DFT level, can provide a full understanding of photosubstitution mechanisms of a monodentate ligand by a solvent water molecule in archetypal ruthenium complexes in explicit water. The simulations show that the photoinduced loss of a monodentate ligand generates an unreactive 16-electron species in a hitherto undescribed pentacoordinated triplet excited state that converts, via an easily accessible crossing point, to a reactive 16-electron singlet ground state, which combines with a solvent water molecule to yield the experimentally observed aqua complex in less than 10 ps. This work paves the way for the rational design of novel photoactive metal complexes relevant for biological applications.

Susceptibility to photoimmune suppression and photocarcinogenesis is greater in male than in female humans and mice and is exacerbated in female estrogen receptor-beta knockout (ER-β-/-) mice. We previously reported that the active vitamin D hormone, 1,25-dihydroxyvitamin D3 (1,25(OH)2D) applied topically protects against ultraviolet radiation (UV)-induction of cutaneous cyclobutane pyrimidine dimers (CPDs) and suppression of contact hypersensitivity (CHS) in female mice. Here we compare these responses in female versus male Skh:hr1 mice, in ER-β-/- versus wild type C57BL/6 mice, and in female ER-blockaded Skh:hr1 mice. Induction of CPDs was significantly greater in male than female Skh:hr1 mice and was more effectively reduced by 1,25(OH)2D in female Skh:hr1 and C57BL/6 mice, than in male Skh:hr1 or ER-β-/- mice respectively. This correlated with reduced sunburn inflammation by 1,25(OH)2D in female but not male Skh:hr1 mice. Furthermore, although 1,25(OH)2D alone dose-dependently suppressed basal CHS responses in male Skh:hr1 and ER-β-/- mice, UV-induced immunosuppression was universally observed. In female Skh:hr1 and C57BL/6 mice, the immunosuppression was decreased by 1,25(OH)2D dose-dependently, but not in male Skh:hr1, ER-β-/- or ER-blockaded mice. These results reveal a sex bias in genetic, inflammatory and immune photoprotection by 1,25(OH)2D favoring female mice, that is dependent on the presence of ER-β.

International audience; Resistance switching properties of nanoscale junctions of spin crossover molecules have received recently much interest. In many cases, this property has been traced back to the variation of molecular orbital energies upon spin transition. However, one can also expect a substantial reorganization of the molecular structure due to charge localization, which calls for a better understanding of the relationship between the redox potential and the spin state of the molecule. To investigate this issue, we carried out a detailed density functional theory and variable temperature cyclic voltammetry investigation of the benchmark compound [Fe(HB(1,2,4-triazol-1-yl)3)2] in solution. We show that, for a correct thermodynamical picture, it is necessary to take into account the charge transfer-induced electronic and structural reorganization as well as spin equilibria in the oxidized and reduced species.

Peptide-based drugs combine advantages of larger biological therapeutics with those of small molecule drugs, but they generally display poor permeability and metabolic stability. Recently, we introduced a new type of peptide bond isostere, in which the backbone carbonyl is replaced with a 3-amino oxetane heterocycle, into short linear peptides with the aim of improving their therapeutic potential. In this study, we have explored the impact of oxetane modification on α-helical peptides to establish whether or not this modification is tolerated in this biologically important structural motif. The oxetane modification was introduced at two positions in a well-characterised helical peptide sequence, and circular dichroism and NMR spectroscopy were used to measure the resulting secondary structure content under different experimental conditions. Our data demonstrated that introduction of an oxetane into the peptide backbone results in a significant loss of helicity, regardless of where in the sequence the modification is placed. The molecular determinants of this destabilisation were then explored using steered molecular dynamics simulations, a computational method analogous to single molecule spectroscopy. Our simulations indicated that oxetane modification introduces a kink in the helical axis, alters the dihedral angles of residues up to three positions away from the modification, and disrupts the (i, i + 4) hydrogen bonding pattern characteristic of α-helices in favour of new, short-range hydrogen bonds. The detailed structural understanding provided in this work can direct future design of chemically modified peptides.

International audience; A complete mechanistic picture for the photochemical release of bpy from the archetypal complex [Ru(bpy)3]2+ is presented for the first time following the description of the ground and lowest triplet potential energy surfaces, as well as their key crossing points, involved in successive elementary steps along pathways towards cis-and trans-[Ru(bpy)2(NCMe)2]2+. This work accounts for two main pathways that are identified involving a) two successive photochemical reactions for photodechelation followed by photorelease of a monodentate bpy ligand, and b) a novel one-photon mechanism in which initial photoexcitation is followed by dechelation, solvent coordination and bpy release processes, all of which occur sequentially within the triplet excited state

First described in 2014, silicone wristband technologies have gained increasing interest as personal chemical monitors. Silicone wristbands are low cost, easy-to-use, sensitive to low chemical concentrations, and sequester a wide range of bioavailable organic chemicals. Wristbands are comfortable, rugged, and do not interfere with daily activities. Between 2014 and early 2019, wristband results have been included in 23 peer-reviewed articles and have been worn by several thousand volunteers on six continents. This chapter provides an overview of silicone wristband passive sampling, considerations for laboratory processing, and research applications. Investigations have ranged from agricultural pesticide exposures in Africa to prenatal polycyclic aromatic hydrocarbon exposures in North America to consumer product-related chemical exposures in South America. Other silicone wearables include pet tags, which have been used to examine flame retardant exposures in context of feline hyperthyroidism. Future directions for wristbands include further investigating chemical mixtures, behavioral health interventions, and disaster-related chemical exposures. As an accessible exposure assessment tool, wristbands will complement research initiatives on the exposome and total exposure health, as well as promote collaborations between researchers and communities.

Superoxide dismutase (SOD) is known to be protective against oxidative stress-mediated skin dysfunction. Here we explore the potential therapeutic activities of RM191A, a novel SOD mimetic, on skin. RM191A is a water soluble, dimeric copper (Cu2+-Cu3+)-centred polyglycine coordination complex. It displays 10-fold higher superoxide quenching activity compared to SOD as well as significant anti-inflammatory activity through beneficial modulation of several significant inflammatory pathways in cells.We tested the therapeutic potential of RM191A in a topical gel using a human skin explant model and observed that it significantly inhibits UV-induced DNA damage in the epidermis and dermis, including cyclobutane pyrimidine dimers (CPD), 8-oxo-guanine (8-oxoG) and 8-nitroguanine (8NGO). RM191A topical gel is found to be safe and non-toxic in mice following month-long daily dosing at 0.19 mL/kg body weight. Moreover, it significantly accelerates excisional wound healing, and reduces 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin inflammation in mice.HighlightsSuperoxide dismutase mimetic RM191A is a highly stable copper (Cu2+-Cu3+)-polyglycine coordination complexRM191A exhibits potent antioxidant (10-fold more than that of superoxide dismutase) properties in vitroRM191A exhibits potent anti-inflammatory properties in vitro and in vivoRM191A protects human skin explants against UV-induced oxidative stress and DNA damageRM191A is non-toxic and readily bioavailable in miceRM191A attenuates TPA-induced skin inflammation and improves wound healing in mice

Cyclic peptides are an important source of new drugs but are challenging to produce synthetically. We show that head-to-tail peptide macrocyclisations are greatly improved, as measured by isolated yields, reaction rates and product distribution, by substitution of one of the backbone amide C═O bonds with an oxetane ring. The cyclisation precursors are easily made by standard solution- or solid-phase peptide synthesis techniques. Macrocyclisations across a range of challenging ring sizes (tetra-, penta- and hexapeptides) are enabled by incorporation of this turn-inducing element. Oxetane incorporation is shown to be superior to other established amino acid modifications such as N-methylation. The positional dependence of the modification on cyclisation efficiency is mapped using a cyclic peptide of sequence LAGAY. We provide the first direct experimental evidence that oxetane modification induces a turn in linear peptide backbones, through the observation of dNN (i, i + 2) and dαN (i, i + 2) NOEs, which offers an explanation for these improvements. For cyclic peptide, cLAGAY, a combination of NMR derived distance restraints and molecular dynamics simulations are used to show that this modification alters the backbone conformation in proximity to the oxetane, with the flexibility of the ring reduced and a new intramolecular H-bond established. Finally, we incorporated an oxetane into a cyclic pentapeptide inhibitor of Aminopeptidase N, a transmembrane metalloprotease overexpressed on the surface of cancer cells. The inhibitor, cCNGRC, displayed similar IC50 values in the presence or absence of an oxetane at the glycine residue, indicating that bioactivity is fully retained upon amide C═O bond replacement.

Superoxide dismutase (SOD) is known to be protective against oxidative stress-mediated skin dysfunction. Here we explore the potential therapeutic activities of RM191A, a novel SOD mimetic, on skin. RM191A is a water-soluble dimeric copper (Cu2+-Cu3+)-centred polyglycine coordination complex. It displays 10-fold higher superoxide quenching activity compared to SOD as well as significant antioxidant, anti-inflammatory and immunomodulatory activities through beneficial modulation of several significant inflammatory cytokines in vitro and in vivo. We tested the therapeutic potential of RM191A in a topical gel using a human skin explant model and observed that it significantly inhibits UV-induced DNA damage in the epidermis and dermis, including cyclobutane pyrimidine dimers (CPD), 8-oxo-guanine (8-oxoG) and 8-nitroguanine (8NGO). RM191A topical gel is found to be non-toxic, non-teratogenic and readily distributed in the body of mice. Moreover, it significantly accelerates excisional wound healing, reduces 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation and attenuates age-associated oxidative stress in skin, demonstrating both skin regenerative and geroprotective properties of RM191A., Graphical abstract Image 1, Highlights • RM191A is a Cu3+ containing coordination complex with 10-fold higher superoxide quenching activity compared to superoxide dismutase. • RM191A exhibits potent antioxidant, anti-inflammatory and immunomodulatory properties in vitro and in vivo. • RM191A protects human skin explants against UV-induced oxidative stress and DNA damage. • RM191A is non-toxic, non-teratogenic and readily bioavailable in mice. • RM191A promotes wound healing, and attenuates TPA-induced inflammation as well as age-associated oxidative stress in mouse skin.

Serum albumin-gold complexes exhibit UV-excitable red luminescence (λem = 640 nm) with unusual Stokes shifts compared with the innate UV/blue fluorescence arising from the aromatic residues. In order to understand the mechanism of this luminescence, we employed limited proteolysis and molecular cloning techniques and assessed the domain containing the red luminophore in bovine serum albumin (BSA) and human serum albumin (HSA). We identified that the luminophore is localized in a domain of serum albumin, residing within the N-terminus half.

The glycopeptide antibiotic vancomycin has been widely used to treat infections of Gram-positive bacteria including Clostridium difficile and methicillin-resistant Staphylococcus aureus. However, since its introduction, high level vancomycin resistance has emerged. The genes responsible require the action of the two-component regulatory system VanSR to induce expression of resistance genes. The mechanism of detection of vancomycin by this two-component system has yet to be elucidated. Diverging evidence in the literature supports activation models in which the VanS protein binds either vancomycin, or Lipid II, to induce resistance. Here we investigated the interaction between vancomycin and VanS from Streptomyces coelicolor (VanSSC), a model Actinomycete. We demonstrate a direct interaction between vancomycin and purified VanSSC, and traced these interactions to the extracellular region of the protein, which we reveal adopts a predominantly α-helical conformation. The VanSSC-binding epitope within vancomycin was mapped to the N-terminus of the peptide chain, distinct from the binding site for Lipid II. In targeting a separate site on vancomycin, the effective VanS ligand concentration includes both free and lipid-bound molecules, facilitating VanS activation. This is the first molecular description of the VanS binding site within vancomycin, and could direct engineering of future therapeutics.

Membrane curvature sensing via helical protein domains, such as those identified in Amphiphysin and ArfGAP1, have been linked to a diverse range of cellular processes. However, these regions can vary significantly between different protein families and thus remain challenging to identify from sequence alone. Greater insight into the protein-lipid interactions that drive this behavior could lead to production of therapeutics that specifically target highly curved membranes. Here we demonstrate the curvature-dependence of membrane binding for an amphipathic helix (APH) in a plant reticulon, namely RTNLB13 from A. thaliana. We utilize solution-state nuclear magnetic resonance spectroscopy to establish the exact location of the APH and map the residues involved in protein-membrane interactions at atomic resolution. We find that the hydrophobic residues making up the membrane binding site are conserved throughout all A. thaliana reticulons. Our results also provide mechanistic insight that leads us to propose that membrane binding by this APH may act as a feedback element, only forming when ER tubules reach a critical size and adding stabilization to these structures without disrupting the bilayer. A shallow hydrophobic binding interface appears to be a feature shared more broadly across helical curvature sensors and would automatically restrict the penetration depth of these structures into the membrane. We also suggest this APH is highly tuned to the composition of the membrane in which it resides, and that this property may be universal in curvature sensors thus rationalizing the variety of mechanisms reported for these functional elements. [Abstract copyright: Copyright © 2019. Published by Elsevier B.V.]

Reticulons are a large family of integral membrane proteins that are ubiquitous in eukaryotes and play a key role in functional remodelling of the endoplasmic reticulum membrane. The reticulon family is especially large in plants, with the Arabidopsis thaliana genome containing twenty-one isoforms. Reticulons vary in length but all contain a conserved C-terminal reticulon homology domain (RHD) that associates with membranes. An understanding of the structure and membrane interactions of RHDs is key to unlocking their mechanism of function, however no three-dimensional structure has been solved. We believe that this is, in part, due to difficulties in obtaining reticulon proteins in yields sufficient for structural study. To address this, we report here the first bacterial overexpression, purification, and biophysical investigation of a reticulon protein from plants, the RTNLB13 protein from A. thaliana. RTNLB13 is the smallest plant reticulon and is made up of a single RHD. We used circular dichroism, SDS-PAGE and analytical ultracentrifugation to reveal that RTNLB13 is 45% α-helical in a number of detergent environments, monomeric at low concentrations, and capable of self-association at higher concentrations. We used solution-state NMR to screen the effect of detergent type on the fold of isotopically-enriched RTNLB13, and found that ∼60% of the expected protein peaks were broadened due to slow dynamics. This broadening points toward a large network of protein-membrane interactions throughout the sequence. We have interpreted our results in light of current literature and suggest a preliminary description of RTNLB13 structure and topology.

International audience; The synthesis and characterization of a set of redox-active iron and ruthenium alkynyl complexes of general formula [[M]Cl(1-p){C equivalent to CC6H5-m(C equivalent to CFlu)(m)}((1+p))][PF6](n) are reported (n = 01; m = 12; [M] = [Fe(eta(5)-C5Me5)(kappa(2)-dppe)] and p = 1 or [M] = [trans-Ru(kappa(2)-dppe)(2)] and p = 01). The linear and third-order nonlinear optical properties of these new organometallic complexes featuring phenylalkynyl ligands functionalized by 2-fluorenyl (Flu) groups were studied in their stable redox states. Their first electronic transitions are assigned with the help of DFT calculations. We show here that these compounds possess significant third-order NLO responses in the near-IR range for molecules of their size. In particular, the remarkably large 2PA activities of the new Ru(II) compounds in the 600-800 nm range (Z-scan) make them attractive nonlinear chromophores. Structure-property studies emphasize the importance of para- versus meta-connection of the 2-fluorenylethynyl units on the phenylalkynyl core and reveal that upon progressing from mono- to bis-alkynyl complexes a further increase of the 2PA cross section can be obtained while maintaining linear transparency in the visible range.

Inadequately repaired post-UV DNA damage results in skin cancers. DNA repair requires energy but skin cells have limited capacity to produce energy after UV insult. We examined whether energy supply is important for DNA repair after UV exposure, in the presence of 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3), which reduces UV-induced DNA damage and photocarcinogenesis in a variety of models. After UV exposure of primary human keratinocytes, the addition of 1,25(OH)2D3 increased unscheduled DNA synthesis, a measure of DNA repair. Oxidative phosphorylation was depleted in UV-irradiated keratinocytes to undetectable levels within an hour of UV irradiation. Treatment with 1,25(OH)2D3 but not vehicle increased glycolysis after UV. 2-Deoxyglucose-dependent inhibition of glycolysis abolished the reduction in cyclobutane pyrimidine dimers by 1,25(OH)2D3, whereas inhibition of oxidative phosphorylation had no effect. 1,25(OH)2D3 increased autophagy and modulated PINK1/Parkin consistent with enhanced mitophagy. These data confirm that energy availability is limited in keratinocytes after exposure to UV. In the presence of 1,25(OH)2D3, glycolysis is enhanced along with energy-conserving processes such as autophagy and mitophagy, resulting in increased repair of cyclobutane pyrimidine dimers and decreased oxidative DNA damage. Increased energy availability in the presence of 1,25(OH)2D3 is an important contributor to DNA repair in skin after UV exposure.

Currently there is a lack of inexpensive, easy-to-use technology to evaluate human exposure to environmental chemicals, including polycyclic aromatic hydrocarbons (PAHs). This is the first study in which silicone wristbands were deployed alongside two traditional personal PAH exposure assessment methods: active air monitoring with samplers (i.e., polyurethane foam (PUF) and filter) housed in backpacks, and biological sampling with urine. We demonstrate that wristbands worn for 48 h in a non-occupational setting recover semivolatile PAHs, and we compare levels of PAHs in wristbands to PAHs in PUFs-filters and to hydroxy-PAH (OH-PAH) biomarkers in urine. We deployed all samplers simultaneously for 48 h on 22 pregnant women in an established urban birth cohort. Each woman provided one spot urine sample at the end of the 48-h period. Wristbands recovered PAHs with similar detection frequencies to PUFs-filters. Of the 62 PAHs tested for in the 22 wristbands, 51 PAHs were detected in at least one wristband. In this cohort of pregnant women, we found more significant correlations between OH-PAHs and PAHs in wristbands than between OH-PAHs and PAHs in PUFs-filters. Only two comparisons between PAHs in PUFs-filters and OH-PAHs correlated significantly (rs = 0.53 and p = 0.01; rs = 0.44 and p = 0.04), whereas six comparisons between PAHs in wristbands and OH-PAHs correlated significantly (rs = 0.44 to 0.76 and p = 0.04 to

International audience; The N®O linkage photoisomerization mechanism in a ruthenium nitrosyl complex, [RuCl(NO)(py)4] 2+ , for which a quasi complete photoconversion between the stable nitrosyl (N-bonded) and metastable isonitrosyl (O-bonded) isomers has been observed under continuous irradiation of the crystal at 473 nm (Cormary et al., Acta Cryst. B 2009, 65, 612-623), is investigated using multiconfigurational second-order perturbation theory (CASPT2). The results support efficient intersystem crossing pathways from the initially excited singlet states to the lowest triplet excited state of metal-to-ligand charge transfer character (3 MLCT). The topology of the involved potential energy surfaces corroborates a complex sequential two-photon 2 photoisomerization mechanism involving nonadiabatic processes in agreement with experimental observations and previous density functional theory calculations.

Wristbands are increasingly used for assessing personal chemical exposures. Unlike some exposure assessment tools, guidelines for wristbands, such as preparation, applicable chemicals, and transport and storage logistics, are lacking. We tested the wristband’s capacity to capture and retain 148 chemicals including polychlorinated biphenyls (PCBs), pesticides, flame retardants, polycyclic aromatic hydrocarbons (PAHs), and volatile organic chemicals (VOCs). The chemicals span a wide range of physical–chemical properties, with log octanol–air partitioning coefficients from 2.1 to 13.7. All chemicals were quantitatively and precisely recovered from initial exposures, averaging 102% recovery with relative SD ≤21%. In simulated transport conditions at +30 °C, SVOCs were stable up to 1 month (average: 104%) and VOC levels were unchanged (average: 99%) for 7 days. During long-term storage at −20 °C up to 3 (VOCs) or 6 months (SVOCs), all chemical levels were stable from chemical degradation or diffusional losses, averaging 110%. Applying a paired wristband/active sampler study with human participants, the first estimates of wristband–air partitioning coefficients for PAHs are presented to aid in environmental air concentration estimates. Extrapolation of these stability results to other chemicals within the same physical–chemical parameters is expected to yield similar results. As we better define wristband characteristics, wristbands can be better integrated in exposure science and epidemiological studies.

Understanding light-induced ligand exchange processes is key to the design of efficient light-releasing prodrugs or photochemically driven functional molecules. Previous mechanistic investigations had highlighted the pivotal role of metal-centered (MC) excited states in the initial ligand loss step. The question remains whether they are equally important in the subsequent ligand capture step. This article reports the mechanistic study of direct acetonitrile coordination onto a 3MC state of [Ru(bpy)3]2+, leading to [Ru(bpy)2(κ1-bpy)(NCMe)]2+ in a 3MLCT (metal-to-ligand charge transfer) state. Coordination of MeCN is indeed accompanied by the decoordination of one pyridine ring of a bpy ligand. As estimated from Nudged Elastic Band calculations, the energy barrier along the minimum energy path is 20 kcal/mol. Interestingly, the orbital analysis conducted along the reaction path has shown that creation of the metallic vacancy can be achieved by reverting the energetic ordering of key dσ* and bpy-based π* orbitals, resulting in the change of electronic configuration from 3MC to 3MLCT. The approach of the NCMe lone pair contributes to destabilizing the dσ* orbital by electrostatic repulsion.

International audience; The elucidation of reaction mechanisms taking place in the excited state is a current challenge for experimental and theoretical chemists. Ru(II) complexes have a long history for photophysics, and there is currently an increasing interest in their photochemistry. Ru(II) complexes provide a vast field of exploration, whether for synthetic purposes, to trigger molecular motions or to release biologically active components. The excited states involved, especially those of MLCT and MC character, are key to the rationalization of their photophysical and photochemical properties. This review focuses on the recent progress in the latter field through several case studies: i) the archetypes [Ru(bpy)3]2+ and [Ru(tpy)2]2+ first serve for the validation of the theoretical methods we are using; ii) then the study of photorelease of a monodentate ligand provides us with novel mechanistic hypotheses; iii) one step further, studying the photorelease mechanism of a bidentate ligand provides us with novel 3MC states of peculiar flattened geometry; iv) finally, returning to [Ru(bpy)3]2+ itself, we will show that the existence of these states can be generalized and probably represent a major player in the description of photoreactivity mechanisms, for ruthenium and possibly several other transition metals.

Fundamental insights into the mechanism of triplet-excited-state interligand energy transfer dynamics and the origin of dual emission for phosphorescent iridium(III) complexes are presented. The complexes [Ir(C ∧N) 2(N ∧N)] + (HC ∧N = 2-phenylpyridine (1a-c), 2-(2,4-difluorophenyl)pyridine (2a-c), 1-benzyl-4-phenyl-1,2,3-triazole (3a-c); N ∧N = 1-benzyl-4-(pyrid-2-yl)-1,2,3-triazole (pytz, a), 1-benzyl-4-(pyrimidin-2-yl)-1,2,3-triazole (pymtz, b), 1-benzyl-4-(pyrazin-2-yl)-1,2,3-triazole (pyztz, c)) are phosphorescent in room-temperature fluid solutions from triplet metal-to-ligand charge transfer ( 3MLCT) states admixed with either ligand-centered ( 3LC) (1a, 2a, and 2b) or ligand-to-ligand charge transfer ( 3LL′CT) character (1c, 2c, and 3a-c). Particularly striking is the observation that pyrimidine-based complex 1b exhibits dual emission from both 3MLCT/ 3LC and 3MLCT/ 3LL′CT states. At 77 K, the 3MLCT/ 3LL′CT component is lost from the photoluminescence spectra of 1b, with emission exclusively arising from its 3MLCT/ 3LC state, while for 2c switching from 3MLCT/ 3LL′CT- to 3MLCT/ 3LC-based emission is observed. Femtosecond transient absorption data reveal distinct spectral signatures characteristic of the population of 3MLCT/ 3LC states for 1a, 2a, and 2b which persist throughout the 3 ns time frame of the experiment. These 3MLCT/ 3LC state signatures are apparent in the transient absorption spectra for 1c and 2c immediately following photoexcitation but rapidly evolve to yield spectral profiles characteristic of their 3MLCT/ 3LL′CT states. Transient data for 1b reveals intermediate behavior: the spectral features of the initially populated 3MLCT/ 3LC state also undergo rapid evolution, although to a lesser extent than that observed for 1c and 2c, behavior assigned to the equilibration of the 3MLCT/ 3LC and 3MLCT/ 3LL′CT states. Density functional theory (DFT) calculations enabled minima to be optimized for both 3MLCT/ 3LC and 3MLCT/ 3LL′CT states of 1a-c and 2a-c. Indeed, two distinct 3MLCT/ 3LC minima were optimized for 1a, 1b, 2a, and 2b distinguished by upon which of the two C ∧N ligands the excited electron resides. The 3MLCT/ 3LC and 3MLCT/ 3LL′CT states for 1b are very close in energy, in excellent agreement with experimental data demonstrating dual emission. Calculated vibrationally resolved emission spectra (VRES) for the complexes are in excellent agreement with experimental data, with the overlay of spectral maxima arising from emission from the 3MLCT/ 3LC and 3MLCT/ 3LL′CT states of 1b convincingly reproducing the observed experimental spectral features. Analysis of the optimized excited-state geometries enable the key structural differences between the 3MLCT/ 3LC and 3MLCT/ 3LL′CT states of the complexes to be identified and quantified. The calculation of interconversion pathways between triplet excited states provides for the first time a through-space mechanism for a photoinduced interligand energy transfer process. Furthermore, examination of structural changes between the possible emitting triplet excited states reveals the key bond vibrations that mediate energy transfer between these states. This work therefore provides for the first time detailed mechanistic insights into the fundamental photophysical processes of this important class of complexes.

Per- and polyfluoroalkyl substances are synthetic environmental pollutants previously used for packaging applications as a grease, oil, and water-resistant coating. Exposure reported in previous studies highlighting potential concerns with public health. This study evaluated performance of coated paper packaging used for microwave popcorn, snacks, and sandwich bags for presence of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS). Current paper packaging materials: seven popcorn bags and three snack and sandwich bags were analysed for PFOA and PFOS and compared to concentrations in microwave popcorn bags between 2005 and 2018. Only two microwave popcorn bags had average PFOA content above the limit of quantitation of 5.11 ng g

Batzer, J. C., Gleason, M. L., Weldon, B., Dixon, P. M., and Nutter, F. W., Jr. 2002. Evaluation of postharvest removal of sooty blotch and flyspeck on apples using sodium hypochlorite, hydrogen peroxide with peroxyacetic acid, and soap. Plant Dis. 86:1325-1332. Postharvest dips of apples (Malus × domestica) in commercial disinfestants were used to remove signs of the flyspeck (FS) pathogen, Schizothyrium pomi, and the sooty blotch (SB) complex (Peltaster fructicola, Leptodontium elatius, and Geastrumia polystigmatis). Apples were dipped for 7 or 15 min in buffered sodium hypochlorite (Agclor 310 plus Decco 312 Buffer) at 200, 400, 500, 600, or 800 ppm chlorine, a mixture of hydrogen peroxide and peroxyacetic acid (Tsunami 100) at 60 ppm/80 ppm, 120 ppm/160 ppm, or 360 ppm/480 ppm, respectively, or soap (Kleen 440), then brushed and rinsed for 30 s on a commercial grading line. Disease severity was assessed as percent diseased area using a quantitative rating system, and by counting the number of colonies of three mycelial types of SB and FS. Percent diseased area on apples was converted to USDA apple grade ratings and retail values. Both assessment methods provided similar results, but the percent-diseased-area method was less labor intensive. A 7-min dip in 800 ppm chlorine resulted in a mean increase from 25 and 55% to 100% Extra Fancy grade for ‘Jonathan’ and ‘Golden Delicious’ apples, respectively, and increased market value by 31 and 14%, respectively. The 7-min, 200-ppm chlorine dip resulted in an increase from 28 and 45% to 92.5 and 96.5% Extra Fancy after treatment for ‘Jonathan’ and ‘Golden Delicious’, respectively. Blemishes were removed more effectively from ‘Jonathan’ and ‘McIntosh’ apples than from ‘Golden Delicious’. Mycelial types of the sooty blotch and flyspeck fungi were removed differentially by the disinfestant dip treatments.

Pethybridge, S. J., Esker, P., Dixon, P., Hay, F., Groom, T., Wilson, C., and Nutter, F. W., Jr. 2007. Quantifying loss caused by ray blight disease in Tasmanian pyrethrum fields. Plant Dis. 91:1116-1121. The efficacy of newly implemented fungicide recommendations on reducing the intensity of ray blight disease caused by Phoma ligulicola to achieve site-specific attainable yield potentials in Tasmanian pyrethrum fields was quantified over two seasons in 46 and 51 fields during the 2003 and 2004 growing seasons, respectively. Disease intensity and yield in two plots (10 × 24 m), one following the commercial fungicide protocol recommendations and the second receiving no fungicide, were assessed in each pyrethrum field. The commercial fungicide protocol consisted of one application of azoxystrobin at 150 g a.i./ha, followed by two applications of a tank mixture of difenoconazole at 125 g a.i./ha and chlorothalonil at 1,008 liters a.i./ha at 14- to 21-day intervals. This program resulted in significant decreases in defoliation severity and the incidence of stems and flowers with ray blight, and increases in the height of stems and number of flowers produced per stem in October and November. In plots receiving the commercial fungicide protocol, the dry weight of flowers was increased by 76 and 68% in 2003 and 2004, respectively. Moreover, pyrethrin yield increased by 81 and 78% when the commercial fungicide protocol was used compared with the nontreated plots. Tobit regression was used to examine the relationships and thresholds among disease intensity measures (defoliation severity, stem severity, and incidence of flowers with ray blight) assessed just prior to harvest. This regression utilized a leftcensored regression model to define subminimal thresholds, as none of the disease intensity measures could be less than 0. Defoliation severity had a threshold of 35.3% before stem severity linearly increased and a threshold of 38.2% before the incidence of flowers with ray blight linearly increased. Finally, the threshold for stem severity was 13.7% before the incidence of flowers with ray blight linearly increased. These thresholds can be used to assist growers in making disease management decisions with the objective of minimizing loss of flowers by maintaining defoliation severity below the critical point at which the incidence of flowers with ray blight begins to linearly increase.

Class II Major Histocompatibility complex (MHC-II) is a polymorphic heterodimer that binds antigen-derived peptides and presents them on the surface of antigen presenting cells. This mechanism of antigen presentation leads to recognition by CD4 T-cells and T-cell activation, making it a critical element of adaptive immune response. For this reason, the structural determinants of MHC-II function have been of great interest for the past 30 years, resulting in a robust structural understanding of the extracellular regions of the complex. However, the membrane-localized regions have also been strongly implicated in protein-protein and protein-lipid interactions that facilitate Class II assembly, transport and function, and it is these regions that are the focus of this review. Here we describe studies that reveal the strong and selective interactions between the transmembrane domains of the MHC α, and invariant chains which, when altered, have broad reaching impacts on antigen presentation and Class II function. We also summarize work that clearly demonstrates the link between membrane lipid composition (particularly the presence of cholesterol) and MHC-II conformation, subsequent peptide binding, and downstream T-cell activation. We have integrated these studies into a comprehensive view of Class II transmembrane domain biology. [Abstract copyright: Copyright © 2018. Published by Elsevier Inc.]

We have quantified the adhesion forces between two-photon polymerization direct laser writing (TPP-DLW) microstructures and glass surfaces with and without an adhesion promoter. Glass surfaces treated with an acryloxy-silane agent produce adhesion forces that are almost three times larger than the forces observed with pristine glass surfaces. Determination of the substrates’ surface free energies suggests that the observed adhesion enhancement is chemical in its nature, implying that covalent bonds are formed between the polymer and the glass by means of the silane agent. The importance of this finding is demonstrated in the successful production of glassy carbon microstructures using TPP-DLW, followed by pyrolysis.

The enzyme carboxypeptidase G2 (CPG2) is used in antibody‐directed enzyme prodrug therapy (ADEPT) to catalyse the formation of an active drug from an inert prodrug. Free CPG2 in the bloodstream must be inhibited before administration of the prodrug in order to avoid a systemic reaction in the patient. Although a few small‐molecule CPG2 inhibitors have been reported, none has been taken forward thus far. This lack of progress is due in part to a lack of structural understanding of the CPG2 active site as well as the absence of small molecules that can block the active site whilst targeting the complex for clearance. The work described here aimed to address both areas. We report the structural/functional impact of extensive point mutation across the putative CPG2 catalytic site and adjacent regions for the first time, revealing that residues outside the catalytic region (K208A, S210A and T357A) are crucial to enzyme activity. We also describe novel molecules that inhibit CPG2 whilst maintaining the accessibility of galactosylated moieties aimed at targeting the enzyme for clearance. This work acts as a platform for the future development of high‐affinity CPG2 inhibitors that occupy new chemical space and will advance the safe application of ADEPT in cancer treatment.\ud \ud

The purpose of the presented protocols is to study the process of Au(III) binding to BSA, yielding conformation change-induced red fluorescence (λ(em) = 640 nm) of BSA-Au(III) complexes. The method adjusts the pH to show that the emergence of the red fluorescence is correlated with the pH-induced equilibrium transitions of the BSA conformations. Red fluorescent BSA-Au(III) complexes can only be formed with an adjustment of pH at or above 9.7, which corresponds to the "A-form" conformation of BSA. The protocol to adjust the BSA to Au molar ratio and to monitor the time-course of the process of Au(III) binding is described. The minimum number of Au(III) per BSA, to produce the red fluorescence, is less than seven. We describe the protocol in steps to illustrate the presence of multiple Au(III) binding sites in BSA. First, by adding copper (Cu(II)) or nickel (Ni(II)) cations followed by Au(III), this method reveals a binding site for Au(III) that is not the red fluorophore. Second, by modifying BSA by thiol capping agents, another nonfluorophore-forming Au(III) binding site is revealed. Third, changing the BSA conformation by cleaving and capping of the disulfide bonds, the possible Au(III) binding site(s) are illustrated. The protocol described, to control the BSA conformations and Au(III) binding, can be generally applied to study the interactions of other proteins and metal cations.

International audience; We have identified a new 3 MC state bearing two elongated RuN bonds to the same ligand in [Ru(bpy) 3 ] 2+. This DFT-optimized structure is a local minimum on the 3 PES. This distal MC state (3 MC cis) is destabilized by less than 2 kcal/mol with respect to the classical MC state (3 MC trans), and energy barriers to populate 3 MC cis and 3 MC trans from the 3 MLCT state are similar according to nudged elastic band minimum energy path calculations. Distortions in the classical 3 MC trans , i.e. elongation of two RuN bonds towards two different bpy ligands, are not expected to favour the formation of ligand-loss photoproducts. On the contrary, the new 3 MC cis could be particularly relevant in the photodegradation of Ru(II) polypyridine complexes

The sequence bendamustine (B) + Irinotecan (I) followed by etoposide (E) + carboplatin (C) was hypothesized to increase progression-free survival (PFS) and overall survival (OS) in untreated extensive-disease small cell lung cancer (EDSCLC) patients compared to historical controls by exploiting mitotic catastrophe. Absent expression of ERCC-1 and expression of topoisomerases were hypothesized to be predictive for PFS and OS. This was a phase I/IIa trial in 30 patients to determine the maximum tolerated dose (MTD) of B + I and the PFS of B + I E + C with secondary end points including overall response rate (ORR) and OS. Biomarkers measured by immunohistochemistry (IHC) obtained from diagnostic specimens were correlated with outcome. The MTD of B + I was not reached. During treatment with B + I, there were two grade 5 toxicities from neutropenic sepsis and metabolic encephalopathy. Other toxicities included fatigue, nausea/vomiting, diarrhea, and weight loss. For the sequence, the PFS and OS were 6.0 months and 10 months, respectively. The ORR for B + I and the sequence were 82% and 83%, respectively. Topoisomerase-2 expression was predictive for TTP and OS, but absent ERCC-1 expression was not, contrary to our hypothesis. B + I is an active regimen in EDSCLC. Toxicities included two grade 5 events but were otherwise manageable. The novel sequence B + I E + C increased PFS and OS compared to historical controls. Correlative studies are conflicting regarding the mechanism of action of this novel sequence.

Topical 1,25-dihydroxyvitamin D (1,25D) and other vitamin D compounds have been shown to protect skin from damage by ultraviolet radiation (UVR) in a process that requires the vitamin D receptor. Yet, while mice which do not express the vitamin D receptor are more susceptible to photocarcinogenesis, mice unable to 1α-hydroxylate 25-hydroxyvitamin D to form 1,25D do not show increased susceptibility to UVR-induced skin tumors. A possible explanation is that an alternative pathway, which does not involve 1α-hydroxylation, may produce photoprotective compounds from vitamin D. The cholesterol side chain cleavage enzyme CYP11A1 is expressed in skin and produces 20-hydroxyvitamin D3 (20OHD) as a major product of vitamin D3. We examined whether topical 20OHD would affect UVR-induced DNA damage, inflammatory edema or immune suppression produced in Skh:hr1 mice. Photoprotection by 20OHD at 23 or 46pmol/cm(2) against cyclobutane pyrimidine dimers (DNA lesions) after UVR in mice was highly effective, up to 98±0.8%, (p

Jarosite flow-through dissolution experiments were conducted in ultrapure water (UPW), pH 2 sulfuric acid, and saturated NaCl and CaCl2 brines at 295–298 K to investigate how hydrologic variables may affect jarosite preservation and reaction products on Mars. K+-based dissolution rates in flowing UPW did not vary significantly with flow rate, indicating that mineral surface reactions control dissolution rates over the range of flow rates investigated. In all of the solutions tested, hydrologic variables do not significantly affect extent of jarosite alteration; therefore, jarosite is equally likely to be preserved in flowing or stagnant waters on Mars. However, increasing flow rate did affect the mineralogy and accumulation of secondary reaction products. Iron release rates in dilute solutions increased as the flow rate increased, likely due to nanoscale iron (hydr)oxide transport in flowing water. Anhydrite formed in CaCl2 brine flow-through experiments despite low temperatures, while metastable gypsum and bassanite were observed in batch experiments. Therefore, observations of the hydration state of calcium sulfate minerals on Mars may provide clues to unravel past salinity and hydrologic conditions as well as temperatures and vapor pressures.

International audience; In this study we examine a large range of organometallic Fe(II) complexes, aiming at identifying computationally the most promising ones in terms of photophysical properties. These complexes combine polypyridine, bis(phosphine) and carbon-bound ligands. DFT has allowed us to establish a comparative Jablonski diagram displaying the lowest singlet, triplet and quintet states. All the proposed FeN 5 C or FeN 3 P 2 C complexes unfavorably possess a lowest triplet state of MC nature. Among the FeN 4 C 2 and FeN 2 P 2 C 2 series, the carbene complexes display the least favorable excited state distribution, also having a low-lying 3 MC state. Validating our design strategy, we are now able to propose seven iron(II) complexes displaying a lowest excited state of 3 MLCT nature. Despite recent efforts and progress, both experimentally and computationally, the quest for luminescent iron(II) complexes is still highly challenging. Aiming at expanding the lifetime of their charge transfer excited states, two opposite strategies have been followed: (i) to increase the ligand field strength through geometric 1,2 or electronic 3-17 modifications, and (ii) to decrease the ligand field strength through steric bulk, obtaining a quintet MC ground state that allows the straightforward population of a 5 MLCT state. 18 Recent studies have brought significant advances, particularly a 100-fold increase in the MLCT lifetime, 3,6,9 reaching 26 ps, 10,18 and efficient TiO 2 sensitization. 5,7,9,14,15,17 Both experimentally-driven and theoretically-driven studies confirm the promising status of certain classes of iron(II) complexes, particularly for photoinduced electron transfer. Our contribution to the field is in the computational design of such complexes, using DFT to get a fast but reliable picture of the excited state distribution. Low-lying charge-tranfer states are desired to bring photophysical properties such as luminescence or electron transfer, while high-lying metal-centered excited states are desired to avoid spin crossover processes and non radiative deactivation. In this respect, we have previously reported a series of mono-and bis(cyclometallated) iron(II) compounds, among which the charge neutral bis(6-phenyl-2,2'-bipyridine)Fe(II) was the most promising

We report new findings on the red fluorescent (λem = 640 nm) bovine serum albumin (BSA)-gold (Au) compound initially described by Xie et al. (J. Am. Chem. Soc. 2009, 131, 888-889) as Au25 nanoclusters. The BSA-Au compounds were further reducible to yield nanoparticles, suggesting that these compounds were BSA-cationic Au complexes. We examined the correlations between BSA conformations (pH-induced as well as denatured) and the resulting fluorescence of BSA-Au complexes, to understand the possible cationic Au binding sites. The red fluorescence of the BSA-Au complex was associated with a particular isoform of BSA, the aged form (pH > 10) of the five pH-dependent BSA conformations, while the other conformations, expanded (pH < 2.7), fast (2.7 < pH < 4.3), normal (4.3 < pH < 8), and basic (8 < pH < 10) did not result in red fluorescence. There could be internal energy transfer mechanisms to produce red fluorescence, deduced from excitation-emission map measurements. The ensemble minimum number of Au(III) per BSA to yield red fluorescence was

International audience; We have identified highly novel photoreactive 3 MC states of ruthenium(II) 4,4'-bi-1,2,3-triazolyl (btz) complexes of the form [Ru(N^N)(btz) 2 ] 2+ and have elucidated the mechanism of the highly unusual experimental observations of photochemical ligand dechelation and concomitant ligand rearrangement reactivity to form unusual photoproducts trans-[Ru(N^N)( 2-btz)( 1-btz)(solvent)] 2+. The triplet metal-to-ligand charge-transfer (3 MLCT) states and classical Jahn-Teller type triplet metal-centred (3 MC) states of the series of complexes [Ru(N^N) 3-n (btz) n ] 2+ (btz = 4,4'-bi-1,2,3-triazolyl; N^N = 2,2'bipyridyl (bpy), n = 0 (1), 1 (2), 2 (3), 3 (5); N^N = 4-{pyrid-2-yl)-1,2,3-triazole (pytz), n = 1 (4)) have been optimised by density functional theory (DFT) and characterised. There is a gradual and significant destabilisation of the 3 MLCT states as the triazole content of the complexes increases, which occurs with a slight stabilisation of the 3 MC states. Whilst consistent with the promotion of photochemical reactivity in the heteroleptic complexes of the series relative to 1, these classical 3 MC states fail to account for the extraordinary ligand rearrangement processes that accompany ligand ejection. Thorough theoretical exploration of the lowest excited triplet potential energy surface (3 PES) here reveals the existence of a new type of 3MC state and the role it plays in the photochemical reactivity of the complexes. This newly discovered state, called MC(F), displays a flattened geometry (indicated by the ‘F’ in the parentheses) which makes it clearly on the path to achieving the coplanarity of the bidentate ligands in the experimentally observed trans-photoproduct. Further novel ‘pentacoodinate’ 3MC states with coplanar bidentate ligands, called MC(P) (where the ‘P’ in the parentheses denotes the pentacoordinate character), were then identified and optimised. The energy barriers between the different triplet states were confirmed to be small which makes all triplet states accessible. Solvent trapping, which occurs on the singlet PES according to Wigner’s rules, is finally achieved by a singlet pentacoordinate species to yield the monosolvento photoproduct. Thus, our calculations not only reveal highly novel 3MC states but more significantly demonstrate their crucial role in the formation of the experimentally observed photoproducts

Background: Previously, we showed that vegetable oil is necessary for carotenoid absorption from salad vegetables. Research is needed to better define the dose effect and its interindividual variation for carotenoids and fat-soluble vitamins.Objective: The objective was to model the dose-response relation between the amount of soybean oil in salad dressing and the absorption of 1) carotenoids, phylloquinone, and tocopherols in salad vegetables and 2) retinyl palmitate formed from the provitamin A carotenoids.Design: Women (n = 12) each consumed 5 vegetable salads with salad dressings containing 0, 2, 4, 8, or 32 g soybean oil. Blood was collected at selected time points. The outcome variables were the chylomicron carotenoid and fat-soluble vitamin area under the curve (AUC) and maximum content in the plasma chylomicron fraction (Cmax). The individual-specific and group-average dose-response relations were investigated by fitting linear mixed-effects random coefficient models.Results: Across the entire 0-32-g range, soybean oil was linearly related to the chylomicron AUC and Cmax values for α-carotene, lycopene, phylloquinone, and retinyl palmitate. Across 0-8 g of soybean oil, there was a linear increase in the chylomicron AUC and Cmax values for β-carotene. Across a more limited 0-4-g range of soybean oil, there were minor linear increases in the chylomicron AUC for lutein and α- and total tocopherol. Absorption of all carotenoids and fat-soluble vitamins was highest with 32 g oil (P < 0.002). For 32 g oil, the interindividual rank order of the chylomicron AUCs was consistent across the carotenoids and fat-soluble vitamins (P < 0.0001).Conclusions: Within the linear range, the average absorption of carotenoids and fat-soluble vitamins could be largely predicted by the soybean oil effect. However, the effect varied widely, and some individuals showed a negligible response. There was a global soybean oil effect such that those who absorbed more of one carotenoid and fat-soluble vitamin also tended to absorb more of the others. This trial was registered at clinicaltrials.gov as NCT02867488.