Apolar Interactions Research Articles

Evaluation of Emulsification Techniques to Optimize the Properties of Chalcone Nanoemulsions for Antifungal Applications.

Background/Objectives: Nanoemulsions (NEs) possess properties that enhance the solubility, bioavailability and therapeutic efficacy of drugs. Chalcones are compounds known for their antifungal properties. In this study, we evaluated different emulsification techniques to create alginate nanoemulsions containing chalcone (1E,4E)-1,5-bis (4-methoxyphenyl) penta-1,4-dien-3-one (DB4OCH3). Our goal was to develop an antifungal formulation targeting Candida albicans strains. Methods: Ultrasound and ultrasound combined with high-speed homogenization techniques were used to prepare alginate-stabilized nanoemulsions. Particle size, zeta potential and encapsulation efficiency were evaluated. Additionally, in vitro release studies were conducted. Results: The combined emulsification technique produced stable nanoparticles with high encapsulation efficiency and antifungal activity, with a minimum inhibitory concentration of 8.75 μg/mL for the nanoemulsions compared to 312 µg/mL for free DB4OCH3. NEs' effectiveness can be attributed to their ability to form nanodroplets efficiently, facilitating the solubilization of the chalcone in the oily phase. The particle size varied between 195.70 ± 2.69 and 243.40 ± 4.49 nm, with an increase in chalcone concentration leading to larger particle sizes. The zeta potential showed values from -91.77 ± 5.58 to -76.90 ± 4.44 mV. The UHS-7 sample exhibited an encapsulation efficiency of 92.10% ± 0.77, with a controlled in vitro release of 83% after 34 h. Molecular docking simulations showed that the aromatic nature of DB4OCH3 resulted in the formation of apolar interactions with aromatic residues located in the active site of the TMK, as observed in their respective co-crystallized inhibitors, within an affinity energy range that enables optimum specificity of the ligand for these two pathways. Pharmacokinetic analyses indicated high passive cell permeability and low hepatic clearance, and phase I metabolism reduces its oral bioavailability and metabolic stability, suggesting a promising active ingredient as an oral drug with control of the daily oral dose administered. Conclusions: The combined nanoemulsification technique led to the formation of finely dispersed nanodroplets that favored the solubilization of the chalcone in the oil phase, which led to a better performance in the antifungal properties. DB4OCH3 shows promise as an oral drug with controlled dosing.

Molecular dynamics simulations of lipid composition and its impact on structural and dynamic properties of skin membrane

The stratum corneum (SC) plays the most important role in the absorption of topical and transdermal drugs. In this study, we developed a multi-layered SC model using coarse-grained molecular dynamics (CGMD) simulations of ceramides, cholesterol, and fatty acids in equimolar proportions, starting from two different initial configurations. In the first approach, all ceramide molecules were initially in the hairpin conformation, and the membrane bilayers were pre-formed. In the second approach, ceramide molecules were introduced in either the hairpin or splayed conformation, with the lipid molecules randomly oriented at the start of the simulation. The aim was to evaluate the effects of lipid chain length on the structural and dynamic properties of SC. By incorporating ceramides and fatty acids of different chain lengths, we simulated the SC membrane in healthy and diseased states. We calculated key structural properties including the thickness, normalized lipid area, lipid tail order parameters, and spatial ordering of the lipids from each system. The results showed that systems with higher ordering and structural integrity contained an equimolar ratio of ceramides (chain length of 24 carbon atoms), fatty acids with chain lengths ≥ of 20 carbon atoms, and cholesterol. In these systems, strong apolar interactions between the ceramide and fatty acid long acyl chains restricted the mobility of the lipid molecules, thereby maintaining a compact lipid headgroup region and high order in the lipid tail region. The simulations also revealed distinct flip-flop mechanisms for cholesterol and fatty acid within the multi-layered membrane. Cholesterol is mostly diffused through the tail-tail interface region of the membrane and could flip-flop in the same bilayer. In contrast, fatty acids flip-flopped between adjacent leaflets of two bilayers in which the tails crossed the thinner headgroup region of the membrane. To conclude, our SC model provides mechanistic insights into lipid mobility and is flexible in its design and composition of different lipids, enabling studies of varying skin conditions.

Effect of anion α-functionalization on the water affinity of thermo-responsive phosphonium acetate-derived ionic liquids

This study presents a facile method for assessing the effect of anion functional group substitution on the water affinity of phosphonium-acetate ionic liquids. By combining the same cation with three different α-substituted carboxylate anions, the effect of anion functional group substitution on the IL miscibility with water and hygroscopicity was experimentally evaluated and rationalized using COSMO-RS sigma profile analysis. Lower critical solution temperature (LCST) phase separation experiments and water vapor partial pressure measurements revealed that there is a stark α-substitution dependency on the affinity of water for acetate [AcO], pivalate [PivO], and trifluoroacetate [TFA] derived tributyl(octyl)phosphonium [P4448] ILs. It was found that the IL water affinities varied as: [P4448][AcO] > [P4448][PivO] > [P4448][TFA]. With the lowest water partial pressure and no LCST driven phase separation, [P4448][AcO] exhibited a high affinity for water. On the other hand, [P4448][PivO] and [P4448][TFA] exhibited LCST-driven phase separation and room temperature immiscibility, respectively, with higher water partial pressures, as a result of relatively weak water affinities. COSMO-RS sigma profile analysis revealed that the aliphatic carboxylate anions should incorporate apolar interactions commensurate with or greater than the polar hydrogen bond acceptor interactions for phase immiscibility of the corresponding IL with water. It was found that the relative magnitudes of apolar and polar interactions, assessed using the anion sigma profile peak intensity ratio (Ir), are directly correlated with the IL water affinity, and inversely correlated with the solution water activity coefficient. Therefore, it was concluded that Ir forms a quantitative link between the structural changes at the molecular level and the bulk water affinity exhibited by the ionic liquid as a whole.

Stabilization of PFAS-contaminated soil with sewage sludge- and wood-based biochar sorbents

Sustainable and effective remediation technologies for the treatment of soil contaminated with per- and polyfluoroalkyl substances (PFAS) are greatly needed. This study investigated the effects of waste-based biochars on the leaching of PFAS from a sandy soil with a low total organic carbon content (TOC) of 0.57 ± 0.04 % impacted by PFAS from aqueous film forming foam (AFFF) dispersed at a former fire-fighting facility. Six different biochars (pyrolyzed at 700–900 °C) were tested, made from clean wood chips (CWC), waste timber (WT), activated waste timber (aWT), two digested sewage sludges (DSS-1 and DSS-2) and de-watered raw sewage sludge (DWSS). Up-flow column percolation tests (15 days and 16 pore volume replacements) with 1 % biochar indicated that the dominant congener in the soil, perfluorooctane sulphonic acid (PFOS) was retained best by the aWT biochar with a 99.9 % reduction in the leachate concentration, followed by sludge-based DWSS (98.9 %) and DSS-2 and DSS-1 (97.8 % and 91.6 %, respectively). The non-activated wood-based biochars (CWC and WT) on the other hand, reduced leaching by <42.4 %. Extrapolating this to field conditions, 90 % leaching of PFOS would occur after 15 y for unamended soil, and after 1200 y and 12,000 y, respectively, for soil amended with 1 % DWSS-amended and aWT biochar. The high effectiveness of aWT and the three sludge-based biochars in reducing PFAS leaching from the soil was attributed largely to high porosity in a pore size range (>1.5 nm) that can accommodate the large PFAS molecules (>1.02–2.20 nm) combined with a high affinity to the biochar matrix. Other factors like anionic exchange capacity could play a contributing role. Sorbent effectiveness was better for long-chain than for short-chain PFAS, due to weaker, apolar interactions between the biochar and the latter's shorter hydrophobic CF2-tails. The findings were the first to demonstrate that locally sourced activated wood-waste biochars and non-activated sewage sludge biochars could be suitable sorbents for the ex situ stabilization and in situ remediation of PFAS-contaminated soil, bringing this technology one step closer to full-scale field testing.

Integration of Lipid-Functionalized Epigallocatechin-3-gallate into PLGA Matrix as a Novel Polyphenol-Based Nanoantioxidant.

The search for polyphenol-based materials with antioxidant activity is a growing research area in the biomedical field. To obtain an efficient and stable nanoantioxidant, a novel biosystem was designed by integrating a lipophilic derivative of epigallocatechin-3-gallate (named EGCG-C18) on the surface of poly(lactic-co-glycolic acid) (PLGA). Poly(vinyl alcohol) (PVA) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-poly(ethylene glycol) (DSPE-PEG2000) were selected as polymeric and lipidic stabilizers, respectively, and their influence on both physical properties and the antioxidant activity of nanoantioxidant was investigated by a combined in silico and experimental approach. Full-atom molecular dynamics (MD) simulations were carried out to describe the different self-assembly processes of all components and the interactions that guided the EGCG-C18 insertion inside the PLGA matrix. Together with infrared spectroscopy results, the formation of an antioxidant lipid shell on the PLGA surface was clear. Dynamic light scattering and transmission electron microscopy showed that in the presence of DSPE-PEG2000, NPs were smaller than those treated with PVA. In addition, the different stabilizers used strongly influenced the ROS-scavenging ability of nanomaterials and this effect was strictly related to the molecular organization of EGCG-C18. MD showed that the apolar interaction between the alkyl chains of DSPE-PEG2000 and EGCG-C18 oriented the phenolic groups of the polyphenol toward the solvent, providing an ability of NP to scavenge hydroxyl radicals over to free EGCG-C18 and PLGA/PVA NPs. Finally, the ability of nanoantioxidants to protect human dermal fibroblasts from cell death induced by oxidative stress has been tested, revealing the high potential of these novel NPs as polyphenol-based materials.

Crystal Structure and NMR of an α,δ-Peptide Foldamer Helix Shows Side-Chains are Well Placed for Bifunctional Catalysis: Application as a Minimalist Aldolase Mimic.

We report the first NMR and X-ray diffraction (XRD) structures of an unusual 13/11-helix (alternating i, i+1 {NH-O=C} and i, i+3 {C=O-H-N} H-bonds) formed by a heteromeric 1 : 1 sequence of α- and δ-amino acids, and demonstrate the application of this framework towards catalysis. Whilst intramolecular hydrogen bonds (IMHBs) are the clear driver of helix formation in this system, we also observe an apolar interaction between the ethyl residue of one δ-amino acid and the cyclohexyl group of the next δ-residue in the sequence that seems to stabilize one type of helix over another. To the best of our knowledge this type of additional stabilization leading to a specific helical preference has not been observed before. Critically, the helix type realized places the α-residue functionalities in positions proximal enough to engage in bifunctional catalysis as demonstrated in the application of our system as a minimalist aldolase mimic.

Crystal Structure and NMR of an α,δ-Peptide Foldamer Helix Shows Side-Chains are Well Placed for Bifunctional Catalysis: Application as a Minimalist Aldolase Mimic.

We report the first NMR and X-ray diffraction (XRD) structures of an unusual 13/11-helix (alternating i, i+1 {NH-O=C} and i, i+3 {C=O-H-N} H-bonds) formed by a heteromeric 1 : 1 sequence of α- and δ-amino acids, and demonstrate the application of this framework towards catalysis. Whilst intramolecular hydrogen bonds (IMHBs) are the clear driver of helix formation in this system, we also observe an apolar interaction between the ethyl residue of one δ-amino acid and the cyclohexyl group of the next δ-residue in the sequence that seems to stabilize one type of helix over another. To the best of our knowledge this type of additional stabilization leading to a specific helical preference has not been observed before. Critically, the helix type realized places the α-residue functionalities in positions proximal enough to engage in bifunctional catalysis as demonstrated in the application of our system as a minimalist aldolase mimic.

Interfacial Dynamics and Growth Modes of β2-Microglobulin Dimers.

Protein aggregation is a complex process, strongly dependent on environmental conditions and highly structurally heterogeneous, both at the final level of fibril structure and intermediate level of oligomerization. Since the first step in aggregation is the formation of a dimer, it is important to clarify how certain properties of the latter (e.g., stability or interface geometry) may play a role in self-association. Here, we report a simple model that represents the dimer's interfacial region by two angles and combine it with a simple computational method to investigate how modulations of the interfacial region occurring on the ns-μs time scale change the dimer's growth mode. To illustrate the proposed methodology, we consider 15 different dimer configurations of the β2m D76N mutant protein equilibrated with long Molecular Dynamics simulations and identify which interfaces lead to limited and unlimited growth modes, having, therefore, different aggregation profiles. We found that despite the highly dynamic nature of the starting configurations, most polymeric growth modes tend to be conserved within the studied time scale. The proposed methodology performs remarkably well taking into consideration the nonspherical morphology of the β2m dimers, which exhibit unstructured termini detached from the protein's core, and the relatively weak binding affinities of their interfaces, which are stabilized by nonspecific apolar interactions. The proposed methodology is general and can be applied to any protein for which a dimer structure has been experimentally determined or computationally predicted.

Exploring functional and structural features of chemically related natural prenylated hydroquinone and benzoic acid from Piper crassinervium (Piperaceae) on bacterial peroxiredoxin inhibition.

Multiple drug resistance (MDR) bacterial strains are responsible by 1.2 million of human deaths all over the world. The pathogens possess efficient enzymes which are able to mitigate the toxicity of reactive oxygen species (ROS) produced by some antibiotics and the host immune cells. Among them, the bacterial peroxiredoxin alkyl hydroperoxide reductase C (AhpC) is able to decompose efficiently several kinds of hydroperoxides. To decompose their substrates AhpC use a reactive cysteine residue (peroxidatic cysteine-CysP) that together with two other polar residues (Thr/Ser and Arg) comprise the catalytic triad of these enzymes and are involved in the substrate targeting/stabilization to allow a bimolecular nucleophilic substitution (SN2) reaction. Additionally to the high efficiency the AhpC is very abundant in the cells and present virulent properties in some bacterial species. Despite the importance of AhpC in bacteria, few studies aimed at using natural compounds as inhibitors of this class of enzymes. Some natural products were identified as human isoforms, presenting as common characteristics a bulk hydrophobic moiety and an α, β-unsaturated carbonylic system able to perform a thiol-Michael reaction. In this work, we evaluated two chemically related natural products: 1,4-dihydroxy-2-(3',7'-dimethyl-1'-oxo-2'E,6'-octadienyl) benzene (C1) and 4-hydroxy-2-(3',7'-dimethyl-1'-oxo-2'E,6'-octadienyl) benzoic acid (C2), both were isolated from branches Piper crassinervium (Piperaceae), over the peroxidase activity of AhpC from Pseudomonas aeruginosa (PaAhpC) and Staphylococcus epidermidis (SeAhpC). By biochemical assays we show that although both compounds can perform the Michael addition reaction, only compound C2 was able to inhibit the PaAhpC peroxidase activity but not SeAhpC, presenting IC50 = 20.3 μM. SDS-PAGE analysis revealed that the compound was not able to perform a thiol-Michael addition, suggesting another inhibition behavior. Using computer-assisted simulations, we also show that an acidic group present in the structure of compound C2 may be involved in the stabilization by polar interactions with the Thr and Arg residues from the catalytic triad and several apolar interactions with hydrophobic residues. Finally, C2 was not able to interfere in the peroxidase activity of the isoform Prx2 from humans or even the thiol proteins of the Trx reducing system from Escherichia coli (EcTrx and EcTrxR), indicating specificity for P. aeruginosa AhpC.

Triazole based novel molecules as potential therapeutic agents: Synthesis, characterization, biological evaluation, in-silico ADME profiling and molecular docking studies

In this study, eight new compounds (7a-h) based on triazole compounds containing ester groups were synthesized with high yields. The structures of the synthesized compounds (7a-h) were elucidated by various spectroscopic methods (element analysis, FT-IR, 1H-(13C) NMR). Antioxidant, anticancer, and α-amylase enzyme inhibition activities of synthesized new triazole derivatives were carried out, and the effects of different groups on the activity were investigated. When the determined antioxidant properties of the compounds were examined, all synthesized compounds showed a moderate radical scavenging effect against radicals depending on the concentration (6.25–200 g/mL). All compounds except the three derivatives were found to have higher IC50 values than the standard drug acarbose (IC50: 891 μg/mL) according to the α-amylase enzyme inhibition results. Compound 7g (IC50: 50 g/mL) was discovered to have nearly eighteen (18) times the activity of the conventional medication acarbose (IC50: 891 μg/mL). Compounds synthesized for anticancer activity studies were screened against the Hela cell line, and the results were compared with standard cis-platinum (IC50: 16.30 μg/mL). Compound 7g (IC50: 19.78 μg/mL) was found to have almost the same activity as cis-platinum. Using Qikprop, the compounds were thoroughly tested for ADME qualities, and none violated any drug similarity standards. According to ADME data, whole physicochemical drug-likeness parameters of molecules remained within defined ranges as stipulated in the Lipinski rules (RO5) and revealed a high bioavailability profile. The molecular docking results with 2QV4 and 4GQR alpha-amylase enzymes demonstrated that all molecules have a high affinity, indicating polar and apolar interaction with critical amino acids in the α-amylase binding pocket.

The periplasmic chaperone Skp prevents misfolding of the secretory lipase A from Pseudomonas aeruginosa.

Pseudomonas aeruginosa is a wide-spread opportunistic human pathogen and a high-risk factor for immunodeficient people and patients with cystic fibrosis. The extracellular lipase A belongs to the virulence factors of P. aeruginosa. Prior to the secretion, the lipase undergoes folding and activation by the periplasmic foldase LipH. At this stage, the enzyme is highly prone to aggregation in mild and high salt concentrations typical for the sputum of cystic fibrosis patients. Here, we demonstrate that the periplasmic chaperone Skp of P. aeruginosa efficiently prevents misfolding of the lipase A in vitro. In vivo experiments in P. aeruginosa show that the lipase secretion is nearly abolished in absence of the endogenous Skp. Small-angle X-ray scattering elucidates the trimeric architecture of P. aeruginosa Skp and identifies two primary conformations of the chaperone, a compact and a widely open. We describe two binding modes of Skp to the lipase, with affinities of 20nM and 2μM, which correspond to 1:1 and 1:2 stoichiometry of the lipase:Skp complex. Two Skp trimers are required to stabilize the lipase via the apolar interactions, which are not affected by elevated salt concentrations. We propose that Skp is a crucial chaperone along the lipase maturation and secretion pathway that ensures stabilization and carry-over of the client to LipH.

2-Aminophenol-based ligands and Cu(II) complexes: Synthesis, characterization, X-ray structure, thermal and electrochemical properties, and in vitro biological evaluation, ADMET study and molecular docking simulation

Two ligands 2-[(2,4-dimethoxybenzylidene)amino]phenol (HA), 2-[(2,5-dimethoxybenzylidene)amino]phenol (HB) and their Cu2+ transition metal complexes were synthesized and characterized by elemental analysis, mass spectra, UV–vis, 1H and 13C NMR (only used for HA and HB) and FTIR methods. Single crystals of the ligands HA and HB were obtained from ethanol solution, and single-crystal X-ray diffraction techniques have elucidated their molecular structures. Thermal properties of the 2-amino phenol-based ligands (HA and HB) and their Cu2+ metal complexes have been investigated by using thermogravimetric (TGA) and differential thermal analyses (DTA) methods. The electrochemical properties of all compounds have been studied in the -1.1 to +1.1 V range. In vitro antimicrobial activity was screened against two gram-positive (Staphylococcus aureus and Bacillus cereus), two gram-negative (Escherichia coli and S. typhimurium), and one fungal strain (Candida albicans) and compounds exhibited bactericidal and fungicidal behavior. The cytotoxic properties of the compounds were evaluated on HUVEC and MCF-7 cells by calculating IC50 values for both cell types. The smallest IC50 values ​​of the compounds tested were 34.19 µM for the HA compound in the MCF-7 cell line, while they were calculated to be 17.67 µM for the HB compound in the HUVEC cell line. In addition to the wet laboratory investigations, the ADMET characteristics of the compounds were thoroughly assessed, and none of them were found to violate any drug similarity rules. The synthesized compounds' physicochemical and pharmacological characteristics stayed within Lipinski's RO5 projected limits and have a high bioavailability profile according to ADMET data. In silico toxicity studies revealed that the compounds did not show AMES toxicity and hepatotoxicity. In silico, target receptor predictions of the compounds were performed, and their potential to be kinase inhibitors was high. Therefore, BRAF (V600E) protein kinase was selected target protein in molecular docking studies. Molecular docking studies revealed that all compounds exhibited a significant affinity for crucial residues in the enzyme's active site, confirming the inhibitory nature of BRAF (V600E) protein kinase, showing both polar and apolar interactions.

Cryo-EM snapshots of a native lysate provide structural insights into a metabolon-embedded transacetylase reaction

Found across all kingdoms of life, 2-keto acid dehydrogenase complexes possess prominent metabolic roles and form major regulatory sites. Although their component structures are known, their higher-order organization is highly heterogeneous, not only across species or tissues but also even within a single cell. Here, we report a cryo-EM structure of the fully active Chaetomium thermophilum pyruvate dehydrogenase complex (PDHc) core scaffold at 3.85 Å resolution (FSC = 0.143) from native cell extracts. By combining cryo-EM with macromolecular docking and molecular dynamics simulations, we resolve all PDHc core scaffold interfaces and dissect the residing transacetylase reaction. Electrostatics attract the lipoyl domain to the transacetylase active site and stabilize the coenzyme A, while apolar interactions position the lipoate in its binding cleft. Our results have direct implications on the structural determinants of the transacetylase reaction and the role of flexible regions in the context of the overall 10 MDa PDHc metabolon architecture.

Solving a solubility problem.

Despite their similarity with surfactants, the mechanism by which hydrotropes assist in solubilizing apolar molecules in water is not totally understood. A mechanism is now proposed that identifies apolar interactions as driving forces of hydrotropy, in agreement with a statistical thermodynamic picture.

Exploring the interaction mechanism of a dicarboxamide fungicide, iprodione with bovine serum albumin

Binding of iprodione (IPR), a dicarboxamide fungicide, to the carrier protein in bovine circulation, bovine serum albumin (BSA) was characterized with the help of fluorescence, absorption, circular dichroism and Fourier transform infrared (FTIR) spectral measurements in combination with computational analysis. The increase in the KSV (Stern–Volmer constant) value with temperature and absorption spectral results characterized the IPR-induced quenching of BSA fluorescence as dynamic quenching. On the other hand, higher value (> 1011 M−1 s−1) of the bimolecular quenching rate constant (kq) suggested complex formation between IPR and BSA. In view of it, increase in KSV value with temperature can be considered as an indication of the involvement of endothermic apolar (hydrophobic) interactions in stabilizing the IPR–BSA complex, as these forces are maximized at higher temperature. A weak binding affinity was anticipated from the values of the binding constant (Ka = 0.83–2.69 × 103 M−1) for IPR–BSA association. Thermodynamic analysis of the binding data further supported contribution of hydrophobic interactions in the IPR–BSA association process. This result was validated by the computational docking analysis. Spectral results from three-dimensional fluorescence and circular dichroism demonstrated microenvironmental changes around BSA fluorophores and protein’s structural (secondary and tertiary) alterations, respectively, upon IPR binding to the protein. Slight variation in the secondary structures of BSA in the presence of IPR was also verified from FTIR spectral results. IPR was found to bind to both site I (subdomain IIA) and site II (subdomain IIIA) of BSA, showing more preference toward site II, as identified by the competitive drug displacement results and supported by the computational analysis.

Structure of the Human ACP-ISD11 Heterodimer.

In recent years, the mammalian mitochondrial protein complex for iron-sulfur cluster assembly has been the focus of important studies. This is partly because of its high degree of relevance in cell metabolism and because mutations of the involved proteins are the cause of several human diseases. Cysteine desulfurase NFS1 is the key enzyme of the complex. At present, it is well-known that the active form of NFS1 is stabilized by the small protein ISD11. In this work, the structure of the human mitochondrial ACP-ISD11 heterodimer was determined at 2.0 Å resolution. ACP-ISD11 forms a cooperative unit stabilized by several ionic interactions, hydrogen bonds, and apolar interactions. The 4'-phosphopantetheine-acyl chain, which is covalently bound to ACP, interacts with several residues of ISD11, modulating together with ACP the foldability of ISD11. Recombinant human ACP-ISD11 was able to interact with the NFS1 desulfurase, thus yielding an active enzyme, and the NFS1/ACP-ISD11 core complex was activated by frataxin and ISCU proteins. Internal motions of ACP-ISD11 were studied by molecular dynamics simulations, showing the persistence of the interactions between both protein chains. The conformation of the dimer is similar to that found in the context of the (NFS1/ACP-ISD11)2 supercomplex core, which contains the Escherichia coli ACP instead of the human variant. This fact suggests a sequential mechanism for supercomplex consolidation, in which the ACP-ISD11 complex may fold independently and, after that, the NFS1 dimer would be stabilized.

Time-Resolved Infrared and Visible Spectroscopy on Cryptochrome aCRY: Basis for Red Light Reception

Cryptochromes function as flavin-binding photoreceptors in bacteria, fungi, algae, land plants, and insects. The discovery of an animal-like cryptochrome in the green alga Chlamydomonas reinhardtii has expanded the spectral range of sensitivity of these receptors from ultraviolet A/blue light to almost the complete visible spectrum. The broadened light response has been explained by the presence of the flavin neutral radical as a chromophore in the dark. Concomitant with photoconversion of the flavin, an unusually long-lived tyrosyl radical with a red-shifted ultraviolet-visible spectrum is formed, which is essential for the function of the receptor. In this study, the microenvironment of this key residue, tyrosine 373, was scrutinized using time-resolved Fourier transform infrared spectroscopy on several variants of animal-like cryptochrome and density functional theory for band assignment. The reduced tyrosine takes on distinct hydrogen bond scenarios depending on the presence of the C-terminal extension and of a neighboring cysteine. Upon radical formation, all variants showed a signal at 1400 cm−1, which we assigned to the ν7′a marker band of the CO stretching mode. The exceptionally strong downshift of this band cannot be attributed to a loss of hydrogen bonding only. Time-resolved ultraviolet-visible spectroscopy on W322F, a mutant of the neighboring tryptophan residue, revealed a decrease of the tyrosyl radical lifetime by almost two orders of magnitude, along with a shift of the absorbance maximum from 416 to 398 nm. These findings strongly support the concept of a π-π stacking as an apolar interaction between Y373 and W322 to be responsible for the characteristics of the tyrosyl radical. This concept of radical stabilization has been unknown to cryptochromes so far but might be highly relevant for other homologs with a tetrad of tryptophans and tyrosines as electron donors.

Synthesis and Gelling Abilities of Polyfunctional Cyclohexane-1,2-dicarboxylic Acid Bisamides: Influence of the Hydroxyl Groups.

New enantiomerically pure C16-alkyl diamides derived from trihydroxy cyclohexane-1,2-dicarboxylic acid have been synthesized from (−)-shikimic acid. The hydroxyl groups in these compounds are free or, alternatively, they present full or partial protection. Their gelling abilities towards several solvents have been tested and rationalized by means of the combined use of Hansen solubility parameters, scanning electron microscopy (SEM), and circular dichroism (CD), as well as computational calculations. All the results allowed us to account for the capability of each type of organogelator to interact with different solvents and for the main mode of aggregation. Thus, compounds with fully protected hydroxyl groups are good organogelators for methanol and ethanol. In contrast, a related compound bearing three free hydroxyl groups is insoluble in water and polar solvents including alcohols but it is able to gelate some low-polarity solvents. This last behavior can be justified by strong hydrogen bonding between molecules of organogelator, which competes advantageously with polar solvent interactions. As an intermediate case, an organogelator with two free hydroxyl groups presents an ambivalent ability to gelate both apolar and polar solvents by means of two aggregation patterns. These involve hydrogen bonding interactions of the unprotected hydroxyl groups in apolar solvents and intermolecular interactions between amide groups in polar ones.

Synthesis and characterization of Sr1-xLaxMnO3/SiOC nanocomposites decorated with 1D nanostructures for high temperature CO2 splitting

1D nanostructures of Lanthanum Strontium Manganite (LSM) are tested as thermochemical catalyst for CO2 splitting. The manganite precursors were incorporated into a ceramic silicon oxycarbide (SiOC) matrix at two different stages during its synthesis to form the nanocomposites. As a result, the LSM nanostructures decorate the large-size pores of the SiOC matrix in form of 1D nanofibers and nanowires. At the same time, the formation of the SiOC units decreases because of the incorporation of these LSM. Moreover, the synthetic strategy strongly affects the surface parameter related to apolar interactions. It turns out that the surface fractal constant of the nanocomposite determines the reactivity of the LSM materials towards CO2. This reactivity has been verified by collecting the spectra of the gases involved in the thermochemical reactions and determining the relative CO2 concentration as a function of the temperature.

Equilibrium partitioning of organic compounds to OASIS HLB® as a function of compound concentration, pH, temperature and salinity

Oasis hydrophilic lipophilic balance® (Oasis HLB) is commonly employed in solid phase extraction (SPE) of environmental contaminants and within polar organic chemical integrative passive samplers (POCIS). In this study batch experiments were carried out to evaluate the relative affinity of a range of relevant organic pollutants to Oasis HLB in aqueous systems. The influence of sorbate concentration, temperature, pH, and salinity on the equilibrium sorption was investigated. Equilibrium partition ratios (KD) of 28 compounds were determined, ranging over three orders of magnitude from 1.16 × 103 L/kg (atenolol) to 1.07 × 106 L/kg (isoproturon). The Freundlich model was able to describe the equilibrium partitioning to Oasis HLB, and an analysis of the thermodynamic parameters revealed the spontaneous and exothermic nature of the partitioning process. Ionic strength had only a minor effect on the partitioning, whereas pH had a considerable effect but only for ionizable compounds. The results show that apolar interactions between the Oasis HLB and analyte mainly determine the equilibrium partitioning. These research findings can be used to optimize the application of SPE and POCIS for analyses of environmental contaminants even in complex mixtures.