Macro and micro enhancers of the 8-anilino-1-naphthalenesulfonate (ANS) fluorescence. Is ANS indeed a hydrophobic probe?

A study on the absorption and fluorescence properties of the 8-anilino-1-naphthalenesulfonate (ANS) fluorescent probe was performed in order to (i) verify the validity of its classification as hydrophobic probe and (ii) to assess the reliability of the interpretation of the ANS fluorescence enhancement upon protein binding as the evidence for the existence of hydrophobic binding sites on the protein molecules. We observed an enhancement of the ANS fluorescence in hydrophilic media: DMSO, polyethylene glycol (PEG400) and glycerol to the values characteristic of ANS complexes with globular proteins, and all ANS fluorescence characteristics (except anisotropy) in PEG400 and in complex with bovine serum albumin are identical. We observed an increase in the ANS fluorescence with a nonzero anisotropy in an aqueous medium in the presence of an amphiphilic cetyltrimethylammonium cation as a result of the formation of the 1:1 complex with ANS. Water molecules quench the fluorescence of ANS. The enhancement of the ANS fluorescence in aqueous media in the presence of fluorescence enhancers is accounted for by their blocking the access of water molecules to the region close to the excited ANS molecule, which is critical for the fluorescence.

Exploring the molecular solvatochromism, stability, reactivity, and non-linear optical response of resveratrol.

CONTEXT: This work analyzes the isomerization effects and solvent contributions to the stability, electronic excitations, reactivity, and non-linear optical properties (NLO) of resveratrol molecules within the formalism of the Density Functional Theory. The findings suggest that resveratrol solvatochromism is significantly influenced by solvent polarization. The electronic and free energies (E and G) indicate that trans is the most stable conformer. The system is classified as a strong nucleophile. However, the analysis of the Fukui functions and the Mulliken charges indicate that cis-trans isomerization jointly affects the reactive indices of the carbon and hydrogen atoms. The results also suggest that solvent is relevant to solvatochromism and the NLO response. Both cis and trans conformers present strong π - π ∗ excitations that undergo a visible hypsochromic change when the polarity of the solvent increases. Once the absorption spectra are connected to the first hyperpolarization ( ß ) by the Oudar and Chemla relation, the hypsochromism of resveratrol is the reason for the drop in the generation of the second harmonic when the ambient polarity decreases. The CAM-B3LYP DFT results suggest that resveratrol is interesting for NLO applications. Depending on the choice of solvent, values ∼ 50 times those observed for urea ( ß = 0.34 × 10 - 34 esu), which is a standard NLO material. METHODS: The optimized geometries of cis and trans isomers of resveratrol in vacuum were obtained using Density Functional Theory (DFT) with the hybrid exchange-correlation function (CAM-B3LYP) and Pople basis set functions, specifically 6-311++G(d,p). The solvent effect on the geometries of both isomers was included using the polarizable continuum model (PCM) with the same level of QM calculation. Vibrational analysis was conducted to confirm that all optimized geometries correspond to the minimum energy. Various electronic properties, including dipole moments, molecular orbitals, transition energy, dipole polarizabilities, and global reactivity parameters, were calculated using both continuum and discrete solvation models based on the sequential QM/MM methodology. All QM calculations were performed with the Gaussian 09 program and the MC simulations with the DICE program. All NLO analysis was carried out using the Multiwfn code.

Interrogating Explicit Solvent Effects on the Mechanism and Site-Selectivity of Aryl Halide Oxidative Addition to L2Pd(0).

We report a study of solvent effects on the rate, selectivity, and mechanism of (hetero)aryl (pseudo)halide oxidative addition to Pd(PCy3)2 as an exemplar of L2Pd(0) species. First, 2-chloro-3-aminopyridine is observed to undergo faster oxidative addition in toluene compared to more polar solvents, which is not consistent with the trend we observe with many other 2-halopyridines. We attribute this to solvent basicity hydrogen-bonding (pKHB) between solvent and substrate. Greater hydrogen-bond donation from the substrate leads to a more electron-rich aromatic system, and therefore slower oxidative addition. We demonstrate how this affects rate and site-selectivity for hydrogen-bond donating substrates. Second, electron-deficient multihalogenated pyridines exhibit improved site-selectivity in polar solvents, which we attribute to different C-X sites undergoing oxidative addition by two different mechanisms. The C-X site that favours the more polar nucleophilic displacement transition state is preferred over the site that favours a less-polar 3-centered transition state. Finally, (hetero)aryl triflates consistently undergo faster oxidative addition in more polar solvents, which we attribute to highly polar nucleophilic displacement transition states. This leads to improved site-selectivity for C-OTf oxidative addition, even in the presence of highly reactive 2-pyridylhalides.

Green Solvent γ-Valerolactone (GVL) Facilitates Photocatalytic C-H Bond Activation.

Solvents can significantly influence chemical reactions in condensed phases. Their critical properties are increasingly recognized in various research domains such as organic synthesis and biomass valorization. However, in semiconductor photocatalysis, solvents are primarily viewed as mediums for dissolving and diffusing substances, with their potential beneficial effects on photocatalytic conversions often overlooked. Additionally, common photocatalysis solvents like acetonitrile (ACN) pose serious safety and environmental concerns. In this study, we demonstrate that novel and safe green solvents, such as γ-valerolactone (GVL), can significantly enhance the performance of semiconductor photocatalysis for C-H bond activation. Non-specific solvent-solute interactions are the primary contributors to increased photocatalytic activity in the self-coupling of benzylic compounds. Specifically, GVL's large dielectric constant and high refractive index lower the energy barrier for the rate-determining C-H bond activation step, facilitating a faster coupling reaction. The versatility of GVL is further demonstrated in reactions with multiple reagents and in various oxidation and reduction photocatalytic systems beyond classic C-H bond activation. This work not only pioneers the use of green solvents but also provides comprehensive insights for proper solvent selection in semiconductor photocatalysis.

Impact of Solvent Electrostatic Environment on Molecular Junctions Probed via Electrochemical Impedance Spectroscopy.

The electrostatic environment around nanoscale molecular junctions modulates charge transport; solvents alter this environment. Methods to directly probe solvent effects require correlating measurements of the local electrostatic environment with charge transport across the metal-molecule-metal junction. Here, we measure the conductance and current-voltage characteristics of molecular wires using a scanning tunneling microscope-break junction (STM-BJ) setup in two commonly used solvents. Our results show that the solvent environment induces shifts in molecular conductance, which we quantify, but more importantly we find that the solvent also impacts the magnitude of current rectification in molecular junctions. By incorporating electrochemical impedance spectroscopy into the STM-BJ setup, we measure the capacitance of the dipole layer formed at the metal-solvent interface and show that rectification can be correlated with solvent capacitance. These results provide a method of quantifying the impact of the solvent environment and a path toward improved environmental control of molecular devices.

Synthesis and Optical Properties of a Novel Hybrid Nanosystem Based on Covalently Modified nSiO2 Nanoparticles with a Curcuminoid Molecule.

A new curcuminoid molecule (3) has been designed and synthesized, containing a central -(CH2)2-COOH chain at the α carbon of the keto-enol moiety in the structure. The carboxylic acid group is added to react with exposed amino groups on silica oxide nanoparticles (nSiO2), forming an amide bond to attach the curcuminoid moiety to the nSiO2 covalently. The Kaiser test quantifies the functionalization degree, yielding 222 µmol of curcuminoid per gram of nanoparticles. The synthesized hybrid nanosystem, nSiO2-NHCO-CCM, displays significant emission properties, with a maximum emission at 538 nm in dichloromethane, similar to curcuminoid 1 (without the central chain), which emits at 565 nm in the same solvent. Solvent-induced spectral effects on the absorption and emission bands of the new hybrid nanosystem are confirmed, similar to those observed for the free curcuminoid (1). The new nanosystem is evaluated in the presence of kerosene in water, showing an emission band at 525 nm as a detection response. The ability of nSiO2-NHCO-CCM to change its fluorescence when interacting with kerosene in water is notable, as it overcomes the limitation caused by the insolubility of free curcuminoid 1 in water, allowing for the exploitation of its properties when connected to the water-stable nanosystem for future detection studies.

Including the Ensemble of Unstructured Conformations in the Analysis of Protein's Native State by High-Pressure NMR Spectroscopy.

The analysis of pressure induced changes in the chemical shift of proteins allows statements on structural fluctuations proteins exhibit at ambient pressure. The inherent issue of separating general pressure effects from structural related effects on the pressure dependence of chemical shifts has so far been addressed by considering the characteristics of random coil peptides on increasing pressure. In this work, chemically and pressure denatured states of the cold shock protein B from Bacillus subtilis (BsCspB) have been assigned in 2D 1H-15N HSQC NMR spectra and their dependence on increasing hydrostatic pressure has been evaluated. The pressure denatured polypeptide chain has been used to separate general from structural related effects on 1H and 15N chemical shifts of native BsCspB and the implications on the interpretation of pressure induced changes in the chemical shift regarding the structure of BsCspB are discussed. It has been found that the ensemble of unstructured conformations of BsCspB shows different responses to increasing pressure than random coil peptides do. Thus, the approach used for considering the general effects that arise when hydrostatic pressure increases changes the structural conclusions that are drawn from high pressure NMR spectroscopic experiments that rely on the analysis of chemical shifts.

Pathway Selection in Temporal Evolution of Supramolecular Polymers of Ionic π-Systems: Amphiphilic Organic Solvent Dictates the Fate of Water.

Understanding solvent-solute interactions is essential to designing and synthesising soft materials with tailor-made functions. Although the interaction of the solute with the solvent mixture is more complex than the single solvent medium, solvent mixtures are exciting to unfold several unforeseen phenomena in supramolecular chemistry. Here, we report two unforeseen pathways observed during the hierarchical assembly of cationic perylene diimides (cPDIs) in water and amphiphilic organic solvent (AOS) mixtures. When the aqueous supramolecular polymers (SPs) of cPDIs are injected into AOS, initially kinetically trapped short SPs are formed, which gradually transform into thermodynamically stable high aspect ratio SP networks. Using various experimental and theoretical investigations, we found that this temporal evolution follows two distinct pathways depending on the nature of the water-AOS interactions. If the AOS is isopropanol (IPA), water is released from cPDIs into bulk IPA due to strong hydrogen bonding interactions, which further decreases the monomer concentration of cPDIs (Pathway-1). In the case of dioxane AOS, cPDI monomer concentration further increases as water is retained among cPDIs (Pathway-2) due to relatively weak interactions between dioxane and water. Interestingly, these two pathways are accelerated by external stimuli such as heat and mechanical agitation.

Silver(i) Perfluoroalcoholates: Synthesis, Structure, and their Use as Transfer Reagents.

Herein we report a general access to silver(i) perfluoroalcoholates, their structure in the solid state and in solution, and their use as transfer reagents. The silver(i) perfluoroalcoholates are prepared by the reaction of AgF with the corresponding perfluorinated carbonyl compounds in acetonitrile and are stable for a prolonged time at -18 °C. X-ray analysis of single crystals of perfluoroalcoholate species showed that two Ag(i) centers are bridged by the alcoholate ligands. In acetonitrile solution, Ag[OCF3] forms different structures as indicated by IR spectroscopy. Furthermore, the silver(i) perfluoroalcoholates can be used as easy-to-handle transfer reagents for the synthesis of Cu[OCF3], Cu[OC2F5], [PPh4][Au(CF3)3(OCF3)], and fluorinated alkyl ethers.

Aromatic-Carbonyl Interactions as an Emerging Type of Non-Covalent Interactions.

Aromatic-carbonyl (Ar···C═O) interactions, attractive interactions between the arene plane and the carbon atom of carbonyl, are in the infancy as one type of new supramolecular bonding forces. Here the study and functionalization of aromatic-carbonyl interactions in solution is reported. A combination of aromatic-carbonyl interactions and dynamic covalent chemistry provided a versatile avenue. The stabilizing role and mechanism of arene-aldehyde/imine interactions are elucidated through crystal structures, NMR studies, and computational evidence. The movement of imine exchange equilibria further allowed the quantification of the interplay between arene-aldehyde/imine interactions and dynamic imine chemistry, with solvent effects offering another handle and matching the electrostatic feature of the interactions. Moreover, arene-aldehyde/imine interactions enabled the reversal of kinetic and thermodynamic selectivity and sorting of dynamic covalent libraries. To show the functional utility diverse modulation of fluorescence signals is realized with arene-aldehyde/imine interactions. The results should find applications in many aspects, including molecular recognition, assemblies, catalysis, and intelligent materials.

Exploring the Influence of Solvents on Electrochemically Etched Porous Silicon Based on Photoluminescence and Surface Morphology Analysis.

Porous silicon (PSi) has promising applications in optoelectronic devices due to its efficient photoluminescence (PL). This study systematically investigates the effects of various organic solvents and their concentrations during electrochemical etching on the resulting PL and surface morphology of PSi. Ethanol, n-butanol, ethylene glycol (EG) and N,N-dimethylformamide (DMF) were employed as solvents in hydrofluoric acid (HF)-based silicon etching. The PL peak position exhibited progressive blue-shifting with increasing ethanol and EG concentrations, accompanied by reductions in the secondary peak intensity and emission linewidth. Comparatively, changes in n-butanol concentration only slightly impacted the main PL peak position. Additionally, distinct morphological transitions were observed for different solvents, with ethanol and n-butanol facilitating uniform single-layer porous structures at higher concentrations in contrast to the excessive etching caused by EG and DMF resulting in PL quenching. These results highlight the complex interdependencies between solvent parameters such as polarity, volatility and viscosity in modulating PSi properties through their influence on surface wetting, diffusion and etching kinetics. The findings provide meaningful guidelines for selecting suitable solvent conditions to tune PSi characteristics for optimized device performance.

Intramolecular Phenyl Transfer from a Boronate to Lithium in the Gas Phase Reveals Crucial Role of Solvation in Transmetalations.

In contrast to its behavior in solution, the adduct [(LiBr)(tBu)(Ph)Bpin]- (pin=pinacol) transfers its phenyl anion from boron to lithium upon fragmentation in the gas phase. Quantum chemical calculations predict this exceptional transmetalation to be exothermic relative to the separated reactants, [(tBu)(Ph)Bpin]- and LiBr, which we attribute to the high phenyl-anion affinity of the coordinatively unsaturated LiBr unit. The addition of a single molecule of tetrahydrofuran drastically reduces the phenyl-anion affinity of LiBr and thereby renders the transmetalation from boron to lithium endothermic. Thus, the probed system highlights the importance of solvation and ligation effects in transmetalations. For correctly predicting the direction, in which these reactions proceed, it is not sufficient to consider the electronegativities or partial charges of the involved metals or metalloids. Instead, the individual coordination states and their changes over the course of the reaction must be taken into account.

Non-Templated Assembly of D5h-Symmetric Pd5L10 Rings by Precise Ligand Angle Adjustment.

We report a series of Pd(II)nL2n coordination rings for which nuclearity is controlled by the binding angle of the corresponding bis-monodentate bridging ligands. Judicious choice of the angle within a family of rather rigid ligands allowed for the first-time to synthesize a homoleptic five-membered Pd5L10 ring that does not require any template to form. We demonstrate that control over the ring size is maintained both in the solid-, solution-, and gas-phase. Two X-ray structures of five-membered rings from ligands with ideal angles (yielding a perfect pentagonal ring) vs. suboptimal angles (resulting in a highly distorted structure) illustrate the importance of the correct ligand geometry. A mathematical model for estimating the expected ring size based on the ligand angle was derived and DFT computations show that ring-strain is the major factor determining the assembly outcome.

Hydrated Formic Acid Clusters and their Interaction with Electrons.

We investigate ion formation in hydrated formic acid (FA) clusters upon collision with electrons of variable energy, focusing on electron ionization at 70 eV (EI) and low-energy (1.5-15 eV) electron attachment (EA). To uncover details about the composition of neutral clusters, we aim to elucidate the ion formation processes in FAM ⋅ WN clusters initiated by interaction with electrons and determine the extent of cluster fragmentation. EI predominantly produces protonated [FAm+H]+ ions, and in FA-rich clusters, the stable ring structures surrounding H3O+ ions are formed. In contrast, EA leads to a competition between the formation of intact [FAm ⋅ Wn]- and dissociated [FAm ⋅ Wn-H]- fragment ions, influenced by the cluster size, level of hydration, and electron energy. Our findings reveal a predisposition of low-energy EA towards forming [FAm ⋅ Wn]-, while higher electron energies tend to favor the formation of [FAm ⋅ Wn-H]- due to intracluster ion-molecule reactions. The comparison of positive and negative ion spectra suggests that the mass spectra of FA-rich clusters may indicate their actual size and composition. On the other hand, the more weakly bound water evaporation from the clusters depends strongly on the ionization. Thus, for the hydrated clusters, the neutral cluster size can hardly be estimated from the mass spectra.

Peptide Stapling by Crosslinking Two Amines with α-Ketoaldehydes through Diverse Modified Glyoxal-Lysine Dimer Linkers.

α-Ketoaldehydes play versatile roles in the ubiquitous natural processes of protein glycation. However, leveraging the reactivity of α-ketoaldehydes for biomedical applications has been challenging. Previously, the reactivity of α-ketoaldehydes with guanidine has been harnessed to design probes for labeling Arg residues on proteins in an aqueous medium. Herein, a highly effective, broadly applicable, and operationally simple protocol for stapling native peptides by crosslinking two amino groups through diverse imidazolium linkers with various α-ketoaldehyde reagents is described. The use of hexafluoroisopropanol as a solvent facilitates rapid and clean reactions under mild conditions and enables unique selectivity for Lys over Arg. The naturally occurring GOLD/MOLD linkers have been expanded to encompass a wide range of modified glyoxal-lysine dimer (OLD) linkers. In a proof-of-concept trial, these modular stapling reactions enabled a convenient two-round strategy to streamline the structure-activity relationship (SAR) study of the wasp venom peptide anoplin, leading to enhanced biological activities.

Solvent and alkyl substitution effects on charge-transfer mediated triplet state generation in BODIPY dyads: a combined computational and experimental study.

Donor-acceptor dyads based on BODIPYs have been recently employed to enhance the formation of triplet excited states with the process of spin-orbit charge transfer intersystem crossing (SOCT-ISC) which does not require introduction of transition metals or other heavy atoms into the molecule. In this work we compare two donor-acceptor dyads based on meso-naphthalenyl BODIPY by combining experimental and computational investigations. The photophysical and electrochemical characterization reveals a significant effect of alkylation of the BODIPY core, disfavoring the SOCT-ISC mechanism for the ethylated BODIPY dyad. This is complemented with a computational investigation carried out to rationalize the influence of ethyl substituents and solvent effects on the electronic structure and efficiency of triplet state population via charge recombination (CR) from the photoinduced electron transfer (PeT) generated charge-transfer (CT) state. Time dependent-density functional theory (TD-DFT) calculations including solvent effects and spin-orbit coupling (SOC) calculations uncover the combined role played by solvent and alkyl substitution on the lateral positions of BODIPY.

Quantification of meropenem in serum and cerebrospinal fluid in children with bacterial meningitis with augmented renal clearance by UPLC-MS/MS.

Meropenem is an ultrabroad-spectrum antimicrobial agent that is often recommended for the treatment of bacterial meningitis (BM) in children. However, a subtherapeutic phenomenon occurred in BM children complicated with augmented renal clearance (ARC) at the recommended dose of meropenem. To support its pharmacokinetics, a sensitive, fast and robust ultra-liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed to measure meropenem concentrations in serum and cerebrospinal fluid (CSF). The method involved protein precipitation, and samples were diluted with a large proportion of water to eliminate solvent effects. The separation of samples was performed on a Waters Acquity™ BEH C18 column (2.1 × 50 mm i.d., 1.7 µm) with a gradient profile. The mobile phases were formic acid-water (1:1000, v/v) and acetonitrile. The linear range was good, with a concentration range of 0.100-100 µg/mL for serum and 0.0400-20.0 µg/mL for CSF. The intra-day and inter-day precisions were less than 8.0%, and the intra-day and inter-day accuracies varied -6.6% from 6.5% for the both serum and CSF. The selectivity, carry-over, dilution integrity, matrix effect, recovery and stability were validated according to international guidelines. The developed UPLC-MS/MS method successfully determined the meropenem concentrations in the serum and CSF of children with BM complicated with ARC. The results indicated that under the recommended dosing regimen (40 mg/kg every 8 h), the time to reach the effective treatment target of 50%T > MIC was only approximately 3 h and lower CSF concentrations of meropenem were observed in children with BM with ARC.

Effect of Guest Solvents on the Ionic Conductivity and Electrochemical Performance of Metal-Organic Framework-Based Magnesium Semi-Solid Electrolytes.

Developing suitable electrolytes is crucial for the advancement of rechargeable magnesium batteries. Recently, metal-organic frameworks (MOFs) have shown a great interest in the field of solid electrolytes for metal ion batteries. However, the ionic conductivity as well as the electrolyte stability in the presence of Mg electrodes are shown to be strongly dependent on the guest solvent used to solvate Mg salts in MOFsSEs. Our measurements showed that full evacuation of the MOF structure before semi-solid electrolytes (sSEs) preparation is crucial for achieving relatively low Mg overpotentials regardless of the ionic conductivity values. Moreover, the behavior of the anode/MOFsSEs interfaces (MOF: α-Mg3 [HCOO]6 ; Mg salt : MgCl2 -Mg[TFSI]2 (1 : 1 wt %); guest solvent: acetone, DMF, DEG, DME and tetraglyme) was investigated by EIS, CV and galvanostatic measurements. The current comparative study of the electrochemical deposition processes of magnesium from MOFsSEs revealed that magnesium deposition/dissolution reactions vary depending on the MOF structure, the guest anion species as well as the nature of the guest solvents.

Solvent Effects on the Chemo- and Site-Selectivity of Transition Metal-Catalyzed Nitrene Transfer Reactions: Alternatives to Chlorinated Solvents.

Transition metal-catalyzed, non-enzymatic nitrene transfer (NT) reactions to selectively transform C-H and C=C bonds to new C-N bonds are a powerful strategy to streamline the preparation of valuable amine building blocks. However, many catalysts for these reactions use environmentally unfriendly solvents that include dichloromethane, chloroform, 1,2-dichloroethane and benzene. We developed a high-throughput experimentation (HTE) protocol for heterogeneous NT reaction mixtures to enable rapid screening of a broad range of solvents for this chemistry. Coupled with the American Chemical Society Pharmaceutical Roundtable (ACSPR) solvent tool, we identified several attractive replacements for chlorinated solvents. Selected catalysts for NT were compared and contrasted using our HTE protocol, including silver supported by N-dentate ligands, dinuclear Rh complexes and Fe/Mn phthalocyanine catalysts.

Solvent and Crystallization Effects on the Dermal Absorption of Hydrophilic and Lipophilic Compounds.

This study probes the mechanisms by which volatile solvents (water, ethanol) and a nonionic surfactant (Triton X-100) influence the skin permeation of dissolved solutes following deposition of small doses onto unoccluded human skin. A secondary objective was to sharpen guidelines for the use of these and other simple solvent systems for dermal safety testing of cosmetic ingredients at finite doses. Four solutes were studied - niacinamide, caffeine, testosterone and geraniol - at doses close to that estimated to saturate the upper layers of the stratum corneum. Methods included tensiometry, visualization of spreading on skin, polarized light microscopy and in vitro permeation testing using radiolabeled solutes. Ethanol, aqueous ethanol and dilute aqueous Triton solutions all yielded surface tensions below 36 mN/m, allowing them to spread easily on the skin, unlike water (72.4 mN/m) which did not spread. Deposition onto skin of niacinamide (32 µg·cm-2) or caffeine (3.2 µg·cm-2) from water and ethanol led to crystalline deposits on the skin surface, whereas the same amounts applied from aqueous ethanol and 2 % Triton did not. Skin permeation of these compounds was inversely correlated to the extent of crystallization. A separate study with caffeine showed the absence of a dose-related skin permeability increase with Triton. Permeation of testosterone (8.2 µg·cm-2) was modestly increased when dosed from aqueous ethanol versus ethanol. Permeation of geraniol (2.9 µg·cm-2) followed the order aqueous ethanol > water ∼ 2 % Triton >> ethanol and was inversely correlated with evaporative loss. We conclude that, under the conditions tested, aqueous ethanol and Triton serve primarily as deposition aids and do not substantially disrupt stratum corneum lipids. Implications for the design of in vitro skin permeability tests are discussed.