Solvatochromism and Nonradiative Decay of Intramolecular Charge‐Transfer Excited States: Bands‐of‐Energy Model,Thermodynamics, and Self‐Organization

The fluctuations of orientation and induction interactions in solution and their impact on the broadening of absorption and fluorescence spectra are considered in terms of a bands‐of‐energy model. Also covered is the application of principles of thermodynamics and self‐organization of systems for calculation of solvatochromic shift, among them a component owing to the work on electronic polarization of solvent at the instant of electronic transition in the solute. The findings on solvatochromic shift and spectral broadening open the way to the calculation of solvent effects on the rate constant of nonradiative transitions. As demonstrated herein for 15 fluorophores, the novel theory of nonradiative decay of the intramolecular charge‐transfer excited states is carried out for dyes and organic compounds of different nature, both for polar and nonpolar media.     

Triplet Energy Transfer between the Primary Donor and Carotenoids in Rhodobacter sphaeroides R-26.1 Reaction Centers Incorporated with Spheroidene Analogs Having Different Extents of π-Electron Conjugation

Abstract— Three carotenoids, spheroidene, 3,4-dihydrospheroidene and 3,4,5,6-tetrahydrospheroidene, having 8, 9 and 10 conjugated carbon-carbon double bonds, respectively, were incorporated into Rhodobacter (Rb.) sphaeroides R-26.1 reaction centers. The extents of binding were found to be 95±5% for spheroidene, 65±5% for 3,4-dihydrospheroidene and 60±10% for 3,4,5,6-tetrahydrospheroidene. The dynamics of the triplet states of the primary donor and carotenoid were measured at room temperature by flash absorption spectroscopy. The carotenoid, spheroidene, was observed to quench the primary donor triplet state. The triplet state of spheroidene that was formed subsequently decayed to the ground state with a lifetime of 7.0±0.5 μs. The primary donor triplet lifetime in the Rb. sphaeroides R-26.1 reaction centers lacking carotenoids was 60±5 μs. Quenching of the primary donor triplet state by the carotenoid was not observed in the Rb. sphaeroides R-26.1 reaction centers containing 3,4-dihydrospheroidene nor in the R-26.1 reaction centers containing 3,4,5,6-tetrahydrospheroidene. Triplet-state electron paramagnetic resonance was also carried out on the samples. The experiments revealed carotenoid triple-state signals in the Rb. sphaeroides R-26.1 reaction centers incorporated with spheroidene, indicating that the primary donor triplet is quenched by the carotenoid. No carotenoid signals were observed from Rb. sphaeroides R-26.1 reaction centers incorporating 3,4-dihydrospheroidene nor in reaction centers incorporating 3,4,5,6-tetrahydrospheroidene. Circular dichroism, steady-state absorbance band shifts accompanying the primary photochemistry in the reaction center and singlet energy transfer from the carotenoid to the primary donor confirm that the carotenoids are bound in the reaction centers and interacting with the primary donor. These studies provide a systematic approach to exploring the effects of carotenoid structure and excited state energy on triplet transfer between the primary donor and carotenoids in reaction centers from photosynthetic bacteria.     

Atomic Force Microscopy of Novel Zeolitic Materials Prepared by Top‐Down Synthesis and ADOR Mechanism

Top‐down synthesis of 2D materials from a parent 3D zeolite with subsequent post‐synthetic modification is an interesting method for synthesis of new materials. Assembly, disassembly, organisation, reassembly (ADOR) processes towards novel materials based on the zeolite UTL are now established. Herein, we present the first study of these materials by atomic force microscopy (AFM). AFM was used to monitor the ADOR process through observation of the changes in crystal surface and step height of the products. UTL surfaces were generally complex and contained grain boundaries and low‐angle intergrowths, in addition to regular terraces. Hydrolysis of UTL to IPC‐1P did not have adverse effects on the surfaces as compared to UTL. The layers remained intact after intercalation and calcination forming novel materials IPC‐2 and IPC‐4. Measured step heights gave good correlation with the X‐ray diffraction determined d₂₀₀‐spacing in these materials. However, swelling gave rise to significant changes to the surface topography, with significantly less regular terrace shapes. The pillared material yielded the roughest surface with ill‐defined surface features. The results support a mechanism for the majority of these materials in which the UTL layers remain intact during the ADOR process as opposed to dissolving and recrystallising during each step.     

Differential Distortion of Purine Substrates by Human and Plasmodium falciparum Hypoxanthine‐Guanine Phosphoribosyltransferase to Catalyse the Formation of Mononucleotides

Plasmodium falciparum (Pf) hypoxanthine‐guanine phosphoribosyltransferase (HGPRT) is a potential therapeutic target. Compared to structurally homologous human enzymes, it has expanded substrate specificity. In this study, 9‐deazapurines are used as in situ probes of the active sites of human and Pf HGPRTs. Through the use of these probes it is found that non‐covalent interactions stabilise the pre‐transition state of the HGPRT‐catalysed reaction. Vibrational spectra reveal that the bound substrates are extensively distorted, the carbonyl bond of nucleobase moiety is weakened and the substrate is destabilised along the reaction coordinate. Raman shifts of the human and Pf enzymes are used to quantify the differing degrees of hydrogen bonding in the homologues. A decreased Raman cross‐section in enzyme‐bound 9‐deazaguanine (9DAG) shows that the phenylalanine residue (Phe186 in human and Phe197 in Pf) of HGPRT stacks with the nucleobase. Differential loss of the Raman cross‐section suggests that the active site is more compact in human HGPRT as compared to the Pf enzyme, and is more so in the phosphoribosyl pyrophosphate (PRPP) complex 9DAG–PRPP–HGPRT than in 9‐deazahypoxanthine (9DAH)–PRPP–HGPRT.     

X‐Ray Crystallography and Free Energy Calculations Reveal the Binding Mechanism of A2A Adenosine Receptor Antagonists

We present a robust protocol based on iterations of free energy perturbation (FEP) calculations, chemical synthesis, biophysical mapping and X‐ray crystallography to reveal the binding mode of an antagonist series to the A_2A adenosine receptor (AR). Eight A_2AAR binding site mutations from biophysical mapping experiments were initially analyzed with sidechain FEP simulations, performed on alternate binding modes. The results distinctively supported one binding mode, which was subsequently used to design new chromone derivatives. Their affinities for the A_2AAR were experimentally determined and investigated through a cycle of ligand‐FEP calculations, validating the binding orientation of the different chemical substituents proposed. Subsequent X‐ray crystallography of the A_2AAR with a low and a high affinity chromone derivative confirmed the predicted binding orientation. The new molecules and structures here reported were driven by free energy calculations, and provide new insights on antagonist binding to the A_2AAR, an emerging target in immuno‐oncology.     

Structure–Activity Relationships of the Antimalarial Agent Artemisinin 10. Synthesis and Antimalarial Activity of Enantiomers of rac-5β-Hydroxy-d-Secoartemisinin and Analogs: Implications Regarding the Mechanism of Action

An efficient synthesis of rac-6-desmethyl-5β–hydroxy-d-secoartemisinin 2, a tricyclic analog of R-(+)-artemisinin 1, was accomplished and the racemate was resolved into the (+)-2b and (−)-2a enantiomers via their Mosher Ester diastereomers. Antimalarial activity resided with only the artemisinin-like enantiomer R-(−)-2a. Several new compounds 9–16, 19a, 19b, 22 and 29 were synthesized from rac-2 but the C-5 secondary hydroxyl group was surprisingly unreactive. For example, the formation of carbamates and Mitsunobu reactions were unsuccessful. In order to assess the unusual reactivity of 2, a single crystal X-ray crystallographic analysis revealed a close intramolecular hydrogen bond from the C-5 alcohol to the oxepane ether oxygen (O-11). All products were tested in vitro against the W-2 and D-6 strains of Plasmodium falciparum. Several of the analogs had moderate activity in comparison to the natural product 1. Iron (II) bromide-promoted rearrangement of 2 gave, in 50% yield, the ring-contracted tetrahydrofuran 22, while the 5-ketone 15 provided a monocyclic methyl ketone 29 (50%). Neither 22 nor 29 possessed in vitro antimalarial activity. These results have implications in regard to the antimalarial mechanism of action of artemisinin.     

Characterization of the Simultaneous Decay Kinetics of Metarhodopsin States II and III in Rhodopsin by Solution‐State NMR Spectroscopy

The mammalian visual dim‐light photoreceptor rhodopsin is considered a prototype G protein‐coupled receptor. Here, we characterize the kinetics of its light‐activation process. Milligram quantities of α,ε‐¹⁵N‐labeled tryptophan rhodopsin were produced in stably transfected HEK293 cells. Assignment of the chemical shifts of the indole signals was achieved by generating the single‐point‐tryptophan to phenylalanine mutants, and the kinetics of each of the five tryptophan residues were recorded. We find kinetic partitioning in rhodopsin decay, including three half‐lives, that reveal two parallel processes subsequent to rhodopsin activation that are related to the photocycle. The meta II and meta III states emerge in parallel with a relative ratio of about 3:1. Transient formation of the meta III state was confirmed by flash photolysis experiments. From analysis of the site‐resolved kinetic data we propose the involvement of the E₂‐loop in the formation of the meta III state.     

Synthesis of Novel Thiazole Derivatives Bearing β-Amino Acid and Aromatic Moieties as Promising Scaffolds for the Development of New Antibacterial and Antifungal Candidates Targeting Multidrug-Resistant Pathogens

Rapidly growing antimicrobial resistance among clinically important bacterial and fungal pathogens accounts for high morbidity and mortality worldwide. Therefore, it is critical to look for new small molecules targeting multidrug-resistant pathogens. Herein, in this paper we report a synthesis, ADME properties, and in vitro antimicrobial activity characterization of novel thiazole derivatives bearing β-amino acid, azole, and aromatic moieties. The in silico ADME characterization revealed that compounds 1–9 meet at least 2 Lipinski drug-like properties while cytotoxicity studies demonstrated low cytotoxicity to Vero cells. Further in vitro antimicrobial activity characterization showed the selective and potent bactericidal activity of 2a–c against Gram-positive pathogens (MIC 1–64 µg/mL) with profound activity against S. aureus (MIC 1–2 µg/mL) harboring genetically defined resistance mechanisms. Furthermore, the compounds 2a–c exhibited antifungal activity against azole resistant A. fumigatus, while only 2b and 5a showed antifungal activity against multidrug resistant yeasts including Candida auris. Collectively, these results demonstrate that thiazole derivatives 2a–c and 5a could be further explored as a promising scaffold for future development of antifungal and antibacterial agents targeting highly resistant pathogenic microorganisms.     

Regioselectivity and Competition of the Paternò–Büchi Reaction and Triplet–Triplet Energy Transfer between Triplet Benzophenones and Pyrimidines: Control by Triplet Energy Levels

The photochemical reaction of a pyrimidine and a ketone occurs either as a Paternò–Büchi (PB) reaction or as energy transfer (ET) from the triplet ketone to the pyrimidine. It is rare for the two types of reactions to occur concurrently, and their competitive mechanism remains unknown. In this work, two classes of products, regioisomeric oxetane(s) ( 2 , 3 ) from a PB reaction and three isomeric dimers of 5‐fluoro‐1,3‐dimethyl uracil (FDMU) ( 4 – 6 ) from a photosensitized dimerization of FDMU, are obtained through the UV irradiation of FDMU with various benzophenones (BPs). The ratio of the two products (oxetanes to dimers) reveals that the two competitive reactions depend strongly on the triplet energy levels (E_T) of the BPs. The BPs with higher E_T values lead to higher proportions of dimers, whereas those with lower E_T values give higher proportions of oxetane(s), with the generation of just two regioisomeric oxetanes for the BP with the lowest E_T of the eight BPs investigated. The ratio of the two oxetanes ( 2 : 3 ) decreases with the BP E_T value. The competitive mechanism for the two types of photochemical reactions is demonstrated through quenching experiments and investigation of temperature effects. Kinetic analysis shows that the rate constants of the two [2+2] photocycloadditions are comparable. Furthermore, in combination with the results of previous studies, we have gained insight into the dependence of the photochemical type and the regioselectivity in the PB reaction on the triplet energy gaps (ΔE) between the pyrimidines and ketones. For ketones with higher E_T values than the pyrimidines, the photochemical reaction is a photosensitized dimerization of the pyrimidine. In the opposite case, a PB reaction occurs, and the lower the E_T of the ketones, the lower the ratio of oxetanes ( 2 : 3 ). When the E_T of values of the ketones are close to those of the pyrimidines, the two reactions occur concurrently, and the higher the E_T of the ketones, the higher the proportion of the dimers. The ratio of oxetanes ( 2 : 3 ) decreases with the E_T value of the BPs.     

CO2 Absorption Mechanism by the Nonaqueous Solvent Consisting of Hindered Amine 2-[(1,1-dimethylethyl)amino]ethanol and Ethylene Glycol

In this work, we studied the CO₂ absorption mechanism by nonaqueous solvent comprising hindered amine 2-[(1,1-dimethylethyl)amino]ethanol (TBAE) and ethylene glycol (EG). The NMR and FTIR results indicated that CO₂ reacted with an -OH group of EG rather than the -OH of TBAE by producing hydroxyethyl carbonate species. A possible reaction pathway was suggested, which involves two steps. In the first step, the acid–base reaction between TBAE and EG generated the anion HO-CH₂-CH₂-O-; in the second step, the O⁻ of HO-CH₂-CH₂-O⁻ attacked the C atom of CO₂, forming carbonate species.     

Constructing Organic D–A–π‐A‐Featured Sensitizers with a Quinoxaline Unit for High‐Efficiency Solar Cells: The Effect of an Auxiliary Acceptor on the Absorption and the Energy Level Alignment

Four organic D–A –π‐A‐featured sensitizers (TQ1, TQ2, IQ1, and IQ2) have been studied for high‐efficiency dye‐sensitized solar cells (DSSCs). We employed an indoline or a triphenylamine unit as the donor, cyanoacetic acid as the acceptor/anchor, and a thiophene moiety as the conjugation bridge. Additionally, an electron‐withdrawing quinoxaline unit was incorporated between the donor and the π‐conjugation unit. These sensitizers show an additional absorption band covering the broad visible range in solution. The contribution from the incorporated quinoxaline was investigated theoretically by using DFT and time‐dependent DFT. The incorporated low‐band‐gap quinoxaline unit as an auxiliary acceptor has several merits, such as decreasing the band gap, optimizing the energy levels, and realizing a facile structural modification on several positions in the quinoxaline unit. As demonstrated, the observed additional absorption band is favorable to the photon‐to‐electron conversion because it corresponds to the efficient electron transitions to the LUMO orbital. Electrochemical impedance spectroscopy (EIS) Bode plots reveal that the replacement of a methoxy group with an octyloxy group can increase the injection electron lifetime by a factor of 2.4. IQ2 and TQ2 can perform well without any co‐adsorbent, successfully suppress the charge recombination from TiO₂ conduction band to I₃^? in the electrolyte, and enhance the electron lifetime, resulting in a decreased dark current and enhanced open circuit voltage (V_oc) values. By using a liquid electrolyte, DSSCs based on dye IQ2 exhibited a broad incident photon‐to‐current conversion efficiency (IPCE) action spectrum and high efficiency (η=8.50 %) with a short circuit current density (J_sc) of 15.65 mA cm^?2, a V_oc value of 776 mV, a fill factor (FF) of 0.70 under AM 1.5 illumination (100 mW cm^?2). Moreover, the overall efficiency remained at 97 % of the initial value after 1000 h of visible‐light soaking.     

Improved solubilization of pyromellitic dianhydride and 4,4′-oxydianiline in ionic liquid by the addition of zwitterion and their polycondensation

Three different ionic liquids were prepared and examined as solvents for polyimide synthesis. The solubility of 4,4′-oxydianiline and pyromellitic dianhydride as starting materials in ionic liquids was first evaluated, and then their polycondensation was carried out. Although these starting materials were hardly soluble in 1-benzyl-3-methylimidazolium bis(trifluoromethane sulfonyl)imide (3), addition of imidazolium type zwitterion, 1-(1-butyl-3-imidazolio)butane-4-sulfonate (ZI), certainly improved their solubility. When 3 containing 40 mol % ZI was used, nothing was phase separated from this mixed solution containing both starting materials after cooling down to room temperature. After preparing prepolymer in 3 containing 40 mol % of ZI at room temperature, polycondensation was carried out in the same solution at 100, 200, and then 300 °C for every 1 h to obtain polyimide. An inherent viscosity of the obtained polyimide (0.05 g in 10 ml concentrated sulfuric acid) was 1.3 dL g⁻¹, higher than that prepared in only 3 (0.9 dL g⁻¹). The higher average molecular weight of the polyimide was attributed to the improved solubility of the starting materials by the addition of ZI that enabled the preparation of the prepolymer, poly(amide acid), without heating before imidation.     

σ‐Insertive Mechanism versus Concerted Non‐insertive Mechanism in the Intramolecular Hydroamination of Aminoalkenes Catalyzed by Phenoxyamine Magnesium Complexes: A Synthetic and Computational Study

The phenoxyamine magnesium complexes [{ONN}MgCH₂Ph] ( 4 a : {ONN}=2,4‐tBu₂‐6‐(CH₂NMeCH₂CH₂NMe₂)C₆H₂O^?; 4 b : {ONN}=4‐tBu‐2‐(CH₂NMeCH₂CH₂NMe₂)‐6‐(SiPh₃)C₆H₂O^?) have been prepared and investigated with respect to their catalytic activity in the intramolecular hydroamination of aminoalkenes. The sterically more shielded triphenylsilyl‐substituted complex 4 b exhibits better thermal stability and higher catalytic activity. Kinetic investigations using complex 4 b in the cyclisation of 1‐allylcyclohexyl)methylamine ( 5 b ), respectively, 2,2‐dimethylpent‐4‐en‐1‐amine ( 5 c ), reveal a first‐order rate dependence on substrate and catalyst concentration. A significant primary kinetic isotope effect of 3.9±0.2 in the cyclisation of 5 b suggests significant N?H bond disruption in the rate‐determining transition state. The stoichiometric reaction of 4 b with 5 c revealed that at least two substrate molecules are required per magnesium centre to facilitate cyclisation. The reaction mechanism was further scrutinized computationally by examination of two rivalling mechanistic pathways. One scenario involves a coordinated amine molecule assisting in a concerted non‐insertive N?C ring closure with concurrent amino proton transfer from the amine onto the olefin, effectively combining the insertion and protonolysis step to a single step. The alternative mechanistic scenario involves a reversible olefin insertion step followed by rate‐determining protonolysis. DFT reveals that a proton‐assisted concerted N?C/C?H bond‐forming pathway is energetically prohibitive in comparison to the kinetically less demanding σ‐insertive pathway (ΔΔG^≠=5.6 kcal mol^?1). Thus, the σ‐insertive pathway is likely traversed exclusively. The DFT predicted total barrier of 23.1 kcal mol^?1 (relative to the {ONN}Mg pyrrolide catalyst resting state) for magnesium?alkyl bond aminolysis matches the experimentally determined Eyring parameter (ΔG^≠=24.1(±0.6) kcal mol^?1 (298 K)) gratifyingly well.     

Mechanism of the Tyrosine Ammonia Lyase Reaction—Tandem Nucleophilic and Electrophilic Enhancement by a Proton Transfer

Quantum mechanics/molecular mechanics calculations in tyrosine ammonia lyase (TAL) ruled out the hypothetical Friedel–Crafts (FC) route for ammonia elimination from L ‐tyrosine due to the high energy of FC intermediates. The calculated pathway from the zwitterionic L ‐tyrosine‐binding state (0.0 kcal mol^?1) to the product‐binding state ((E)‐coumarate+H₂N? MIO; ?24.0 kcal mol^?1; MIO=3,5‐dihydro‐5‐methylidene‐4H‐imidazol‐4‐one) involves an intermediate (IS, ?19.9 kcal mol^?1), which has a covalent bond between the N atom of the substrate and MIO, as well as two transition states (TS1 and TS2). TS1 (14.4 kcal mol^?1) corresponds to a proton transfer from the substrate to the N1 atom of MIO by Tyr300? OH. Thus, a tandem nucleophilic activation of the substrate and electrophilic activation of MIO happens. TS2 (5.2 kcal mol^?1) indicates a concerted C? N bond breaking of the N‐MIO intermediate and deprotonation of the pro‐S β position by Tyr60. Calculations elucidate the role of enzymic bases (Tyr60 and Tyr300) and other catalytically relevant residues (Asn203, Arg303, and Asn333, Asn435), which are fully conserved in the amino acid sequences and in 3D structures of all known MIO‐containing ammonia lyases and 2,3‐aminomutases.     

A Novel Role of Vesicles as Templates for the Oxidation and Oligomerization of p‐Aminodiphenylamine by Cytochrome c

The oxidation and subsequent oligo‐ or polymerization of aniline or the N‐C‐para coupled aniline dimer p‐aminodiphenylamine (N‐phenyl‐1,4‐phenylenediamine) with H₂O₂‐dependent heme peroxidases in aqueous medium at pH = 4.3 is strongly influenced in a positive way by the presence of anionic polymers, micelles or vesicles as soft ‘templates’ (macromolecular or polymolecular additives), to yield products which resemble the emeraldine salt form of polyaniline (PANI‐ES). The positive effect the templates exert on the reaction mainly originates from interactions between the templates and the monomers, reaction intermediates and products, whereby the reaction occurs localized in the vicinity of the templates, suppressing undesired side reactions. As shown in the present work, the templates may even play an additional role, depending on the type of catalyst. Through interactions between the heme protein cytochrome c and anionic vesicles, cytochrome c gains increased peroxidase activity. In this way, the templates not only serve for hosting the oxidation and oligo‐ or polymerization reactions for obtaining PANI‐ES type products, but also simultaneously activate the catalyst in order to trigger the reaction.     

Formation and Thermal Stability of Gold–Silica Nanohybrids: Insight into the Mechanism and Morphology by Electron Tomography

Gold–silica hybrids are appealing in different fields of applications like catalysis, sensorics, drug delivery, and biotechnology. In most cases, the morphology and distribution of the heterounits play significant roles in their functional behavior. Methods of synthesizing these hybrids, with variable ordering of the heterounits, are replete; however, a complete characterization in three dimensions could not be achieved yet. A simple route to the synthesis of Au‐decorated SiO₂ spheres is demonstrated and a study on the 3D ordering of the heterounits by scanning transmission electron microscopy (STEM) tomography is presented—at the final stage, intermediate stages of formation, and after heating the hybrid. The final hybrid evolves from a soft self‐assembled structure of Au nanoparticles. The hybrid shows good thermal stability up to 400 °C, beyond which the Au particles start migrating inside the SiO₂ matrix. This study provides an insight in the formation mechanism and thermal stability of the structures which are crucial factors for designing and applying such hybrids in fields of catalysis and biotechnology. As the method is general, it can be applied to make similar hybrids based on SiO₂ by tuning the reaction chemistry as needed.     

A Novel Cell Design for the Improved Stripping Voltammetric Detection of Zn(II), Cd(II), and Pb(II) on Commercial Screen‐Printed Strips by Bismuth Codeposition in Stirred Solutions

A novel electrochemical cell design is proposed to allow fast, reproducible and highly efficient convective transport of dissolved substances to screen‐printed electrochemical three‐electrode strips mounted on miniaturized plastic vessels, with the goal of improving detection limits in disposable electrochemical stripping field sensors. The experimental configuration has been tested for accumulation of the selected heavy metals ions Zn(II), Cd(II), and Pb(II), codeposited with bismuth ions on a carbon disk screen‐printed working electrode before detection by square wave anodic stripping voltammetry. Chemical and instrumental variables of the proposed device and associate electrochemical method were optimized. Selected parameters gave detection limits in the low ng mL^?1 range with moderate deposition time (120 s). Practical applicability was tested on certified water and real samples (tap water and waste water), with acceptable results, suggesting potential usefulness for field environmental monitoring of heavy metals.     

Characterization of the Intermediate in and Identification of the Repair Mechanism of (6‐4) Photolesions by Photolyases

Quantum mechanics/molecular mechanics calculations are employed to assign previously recorded experimental spectroscopic signatures of the intermediates occurring during the photo‐induced repair of (6‐4) photolesions by photolyases to specific molecular structures. Based on this close comparison of experiment and theory it is demonstrated that the acting repair mechanism involves proton transfer from the protonated His365 to the N3′ nitrogen of the lesion, which proceeds simultaneously with intramolecular OH transfer along an oxetane‐like transition state.