Performance analysis of un-doped and doped titania (TiO 2 ) as an electron transport layer (ETL) for perovskite solar cells.

CONTEXT: Density functional theory (DFT) calculations are carried out on pure and doped rutile TiO 2 . The bandgap (E g ) for pristine, S-doped, Fe-doped, and Fe/S co-doped materials is direct, with values of 2.98 eV, 2.18 eV, 1.58 eV, and 1.40 eV. The effective mass of charge carriers (m*) and ratio of effective masses of holes to effective masses of electrons (R) are also investigated, and it is discovered that Fe/S co-doped materials have the lowest charge carrier recombination rate. The Fe/S co-doped material has the highest ε ( ω ) . α ( ω ) of doped materials shifted into the visible range. Due to the high dopant concentration in Fe and Fe/S-doped cases, the E g is lowered to a relatively small value; hence, only pristine and S-doped materials are verified as electron transport layer (ETL). A solar cell device analysis employing pure and S-doped rutile TiO 2 as ETL is completed using DFT-derived parameters in SCAPS-1D modeling software for the first time. For the optimized solar cells, current-voltage (IV) characteristics, quantum efficiency (QE), capacitance-voltage (CV) characteristics, and capacitance-frequency (Cf) characteristics are provided. The aim of the present study is to improve efficiency of perovskite solar cell by doping as well as to improve accuracy of simulation by applying DFT extracted parameters as input. From the analysis, improvement is found in efficiency of doped TiO 2 compared to un-doped TiO 2 . The efficiency of the PSC with S-doped ETL is 1.418% higher than the PSC with un-doped ETL. METHOD: Quantumwise Automistic Tool Kit (ATK) is used to extract DFT parameters. Using these DFT parameters as input in SCAPS-1D (Solar Cell Capacitance Simulator), solar cells for doped and un-doped material are simulated. The density functional theory (DFT)-based orthogonalized linear combination of atomic orbital (OLCAO) technique is used. Structural optimization is done using the LBFGS (Limited-memory Broyden-Fletcher-Goldfarb-Shanno). PBESol-GGA (Perdew-Burke-Ernzerhof solid-generalized gradient approximation) is applied as exchange correlation for calculating structural parameters, while MGGA-TB09 (meta-generalized gradient approximation-Tran and Blaha) is applied as exchange correlation for calculating optical and electronic properties.

Unusual redox stability of pentavalent uranium with hetero-bifunctional phosphonocarboxylate: insight into aqueous speciation.

The +5 state is an unusual oxidation state of uranium due to its instability in the aqueous phase. As a result, gaining information about its aqueous speciation is extremely difficult. The present work is an attempt in that direction and it provides insight into the existence of a new pentavalent species in the presence of hetero-bifunctional phosphonocarboxylate (PC) chelators, other than the carbonate ion, in the aqueous medium. The aqueous chemistry of pentavalent uranium species with three environmentally relevant PCs was probed using electrochemical and DFT methods to understand the redox energy and kinetics of conversion of the U(VI)/U(V) couple, stability, structure, stoichiometry, binding modes, etc. Interestingly, pentavalent uranium complexes with PCs are quite persistent over a wide range of pH starting from acidic to alkaline conditions. The PC chelators block the cation-cation interaction (CCI) of U(V) through strong hetero-bidentate chelation and intermolecular hydrogen bonding (IMHB) interactions which stabilize the pentavalent metal ion against disproportionation. For uranyl species in the presence of PCs, acting as chelators, CV plots were obtained at varying pH values from 2 to 8. The obtained results indicate an irreversible single redox peak involving U(VI) to U(V) conversion and association of a coupled chemical reaction with the electron transfer step. ESI-MS studies were performed to understand the speciation effect on the U(VI)/U(V) redox couple with varying pH. Speciation modelling of U(V) with the PC ligands was carried out, which indicated that the U(V) is redox stable in nearly 47% of the pH region in the presence of the PCs as compared to the carboxylate-based chelators. The free energy and reduction potential of the U(V) complexes and the reduction free energy and disproportionation free energy for the U(VI)/U(V) couple were determined by DFT computations in the presence of the PCs. In situ spectroelectrochemical spectra were recorded to provide evidence for the existence of U(V) species with PCs in the aqueous medium and to acquire its absorption spectra. The present study is highly significant for understanding the coordination chemistry of pentavalent uranium species, accurate modelling of uranium, and isolation of U(V).

In-Situ-Generated Fluoride-Assisted Rapid Dissolution of Uranium Oxides by Ionic Liquids.

A quantitative, rapid, endothermic dissolution of U3O8 in C4mim·PF6 (1-alkyl-3-methyl imidazolium hexafluorophosphate) has been achieved within 2 h at 65 °C by in situ generated fluoride ions by pre-equilibrating the ionic liquid with suitable concentrations of nitric acid. The efficiency of the dissolution followed the trend: UO3 > UO2 > U3O8. The fluoride generation was found to increase with the concentration of nitric acid being equilibrated, the water content of the ionic liquid, and also the time of equilibration. The rate of dissolution of U3O8 followed the trend: C4mim·PF6> C6mim·PF6 > C8mim·PF6. The maximum loading observed for the present case was 200 mg mL-1 which is considered to be quite high with an ionic liquid. The effects of different acid pre-equilibration (HClO4, HCl) on F- generation and subsequent dissolution characteristics have also been investigated. The in situ F- generation, as well as U3O8 dissolution, were found to predominantly follow a pseudo-second-order rate kinetics, while the rate constants for U3O8 dissolution were found to be higher than that of F- generation. The dissolved uranium was successfully electrodeposited on a Cu plate, as confirmed by EDXRF, while the formation of UO2 was revealed from the XRD pattern of the deposit.

Influence of protein nativity on the stability of bovine serum albumin coated microbubbles.

Protein-coated microbubbles have become one of the emerging platforms in biomedical research as theranostic agents. In recent years, microbubbles have been extensively used as ultrasound contrast agents and carriers of molecular cargoes, pertaining to which several studies have focused on tuning the properties of these bubbles to achieve a higher degree of biocompatibility and extended stability. Synthesis of microbubbles has so far been traditionally carried out with pre-heated proteins like bovine serum albumin (BSA) as shell coatings, owing to the ease in making BSA crosslinked structures through disulfide bridge formation. We, however, have performed experiments to demonstrate that air core microbubbles formed with native BSA are more stable compared with those formed using denatured BSA. The experimental observations have been supported with analytical modeling and computational studies, which offer insights into the effect of BSA conformation in stabilizing the microbubbles shells and prolonging their lifetimes.

Experimental and Theoretical Insight into the Ionic Liquid-Mediated Complexation of Trivalent Lanthanides with ß-Diketone and Its Fluorinated Analogue.

A multitechnique approach with theoretical insights has been employed to understand the complexation of trivalent lanthanides with two ß-diketones, viz. 1-phenyl-1,3-butanedione (L1) and 4,4,4-trifluoro-1-phenyl-1,3-butanedione (L2), in an ionic liquid (C6mim·NTf2). UV-vis spectral analysis of complexation using Nd3+ revealed the predominance of ML2+ and ML4- species. The stability constants for the PB complexes were higher (ß2 ∼ 10.45 ± 0.05, ß4 ∼ 15.51 ± 0.05) than those for the TPB (ß2 ∼ 7.56 ± 0.05, ß4 ∼ 13.19 ± 0.06). The photoluminescence titration using Eu3+ corroborated the same observations with slightly higher stability constants, probably due to the higher ionic potential of Eu3+. The more asymmetric (AL2ML4 ∼ 5.2) Eu-L2 complex was found to contain one water molecule in the primary coordination sphere of Eu3+ with more covalency of the Eu3+-O bond (Ω2L1 = 8.5 × 10-20, Ω4L1 = 1.3 × 10-20) compared to the less asymmetric Eu-L1 complex (AL1ML4 ∼ 3.5) with two water molecules having less Eu-O covalency (Judd-Offelt parameters: Ω2L1 = 7.3 × 10-20, Ω4L1 = 1.0 × 10-20). Liquid-liquid extraction studies involving Nd3+ and Eu3+ revealed the formation of the ML4- complex following an 'anion exchange' mechanism. The shift of the enol peak from 1176 to 1138 cm-1 on the complexation of the ß-diketones with Eu3+ was confirmed from the FTIR spectra. 1H NMR titration of the ß-diketones with La(NTf2)3 evidenced the participation of α-H of the ß-diketones and protons at C2, C4, and C5 positions of the methylimidazolium ring. For the ML2 complex, 4 donor O atoms are suggested to coordinate to the trivalent lanthanides with bond distances of 2.3297-2.411 Å for La-O, 2.206-2.236 Å for Eu-O, and 2.217-2.268 Å for Nd-O, respectively, while for the ML4 complex, 8 donor O atoms were coordinated with bond lengths of 2.506-2.559 Å for La-O, 2.367-2.447 Å for Eu-O, and 2.408-2.476 Å for Nd-O. The Nd3+ ion was higher by 9.7 kcal·mol-1 than that of the La3+ ion for the 1:4 complex. The complexation energy with L1 was quite higher than that with L2 for both 1:2 and 1:4 complexes. Using cyclic voltammetry, the redox behavior of trivalent lanthanides Eu and Gd with ß-diketonate in ionic liquid medium was probed and their redox energetic and kinetic parameters were determined.

Network approach to understand biological systems: From single to multilayer networks.

Network theory has led to the abstraction of many real-world systems and enabled their modelling as simple networks comprising nodes and edges. In particular, in the field of biological sciences, network theory provides a robust framework to capture the complexity inherent to biological systems. Networks in biology have been modelled at different scales, starting from cells to population levels. These models have provided crucial insights into the evolution, mechanism, and functions of several biological systems. However, most natural and engineered systems are composed of multiple subsystems and layers of connectivity. A multilayer network paradigm has proven useful in understanding such systems. Here, we have briefly introduced the network formalism of modelling biological systems at various levels. This is followed by an introduction to multilayer networks. Multilayer networks have been utilized to model biological systems at multiple scales ranging from protein-protein interactions, transcription and metabolic networks, to ecological networks involving interactions between species. Recent advances in studying the structure and dynamics of such multilayer networks have enabled a better understanding of the complexity in these biological systems. Finally, we discuss the recent advances in studying the structure and dynamics of such multilayered networks followed by the challenges and future prospects.

Chemical and Redox Speciation of Uranyl with Three Environmentally Relevant Bifunctional Chelates: Multi-Technique Approach Combined with Theoretical Estimations.

Carbon and phosphorous are two primary elements common to the bio-geosphere and are omnipresent in both biotic and abiotic arenas. Phosphonate and carboxylate are considered as building blocks of glyphosate and humic substances and constituents of the cellular wall of bacteria and are the driving functionalities for most of the chemical interactions involving these two elements. Phosphonocarboxylates, a combination of both the functionalities in one moiety, are ideal models to dig deep into for understanding the chemical interactions of the two functional groups with metal ions. Phosphorous and carbon majorly exist as inorganic/organic phosphate and carboxylate, respectively, in the bio-geosphere. Aquatic contamination is a major concern for uranium, and the presence of complexing agents would alter the uranium concentrations in aquifers. Determination of solution thermodynamic parameters, speciation plots, redox patterns, Eh-pH diagrams, coordination structures, and molecular-level understanding by density functional theory calculations was carried out to interpret the uranyl (UO22+) interaction with three environmentally relevant phosphonocarboxylates, namely, phosphono-formic acid (PFA), phosphono-acetic acid (PAA), and phosphono-propanoic acid (PPA). UO22+ forms 1:1 complexes with the three phosphonocarboxylates in the monoprotonated form, having nearly the same stability, and the complexes [UO2(PFAH)], [UO2(PAAH)], and [UO2(PPAH)] involve chelate formation of five, six, and seven membered rings, respectively, through the participation of an oxygen each from the carboxylate and phosphonate, strengthened by an intra-molecular hydrogen bonding through the proton of the phosphonate moiety with uranyl oxygen. The complex formations are favored both enthalpically and entropically, with the latter being more contributive to the overall free energy of formation. The redox speciation showed an aqueous soluble complex formation over a wide pH range of 1-8. Electrospray ionization mass spectrometry and extended X-ray absorption fine structure established the coordination modes, which are further corroborated by density functional calculations. The knowledge gained from the present studies provide potential inputs in framing the cleanup, sequestering, microbial, and bio-remediation strategies for uranyl from aquatic environments.

Strong Anharmonicity-Induced Low Thermal Conductivity and High n-type Mobility in the Topological Insulator Bi1.1 Sb0.9 Te2 S.

Intrinsically low lattice thermal conductivity (κlat ) while maintaining the high carrier mobility (µ) is of the utmost importance for thermoelectrics. Topological insulators (TI) can possess high µ due to the metallic surface states. TIs with heavy constituents and layered structure can give rise to high anharmonicity and are expected to show low κlat . Here, we demonstrate that Bi1.1 Sb0.9 Te2 S (BSTS), which is a 3D bulk TI, exhibits ultra-low κlat of 0.46 Wm-1 K-1 along with high µ of ≈401 cm2  V-1 s-1 . Sound velocity measurements and theoretical calculations suggest that chemical bonding hierarchy and high anharmonicity play a crucial role behind such ultra-low κlat . BSTS possesses low energy optical phonons which strongly couple with the heat carrying acoustic phonons leading to ultra-low κlat . Further, Cl has been doped at the S site of BSTS which increases the electron concentration and reduces the κlat resulting in a promising n-type thermoelectric figure of merit (zT) of ≈0.6 at 573 K.

Light-Control over Casein Kinase 1δ Activity with Photopharmacology: A Clear Case for Arylazopyrazole-Based Inhibitors.

Protein kinases are responsible for healthy cellular processes and signalling pathways, and their dysfunction is the basis of many pathologies. There are numerous small molecule inhibitors of protein kinases that systemically regulate dysfunctional signalling processes. However, attaining selectivity in kinase inhibition within the complex human kinome is still a challenge that inspires unconventional approaches. One of those approaches is photopharmacology, which uses light-controlled bioactive molecules to selectively activate drugs only at the intended space and time, thereby avoiding side effects outside of the irradiated area. Still, in the context of kinase inhibition, photopharmacology has thus far been rather unsuccessful in providing light-controlled drugs. Here, we present the discovery and optimisation of a photoswitchable inhibitor of casein kinase 1δ (CK1δ), important for the control of cell differentiation, circadian rhythm, DNA repair, apoptosis, and numerous other signalling processes. Varying the position at which the light-responsive azobenzene moiety has been introduced into a known CK1δ inhibitor, LH846, revealed the preferred regioisomer for efficient photo-modulation of inhibitory activity, but the photoswitchable inhibitor suffered from sub-optimal (photo)chemical properties. Replacement of the bis-phenyl azobenzene group with the arylazopyrazole moiety yielded a superior photoswitch with very high photostationary state distributions, increased solubility and a 10-fold difference in activity between irradiated and thermally adapted samples. The reasons behind those findings are explored with molecular docking and molecular dynamics simulations. Results described here show how the evaluation of privileged molecular architecture, followed by the optimisation of the photoswitchable unit, is a valuable strategy for the challenging design of the photoswitchable kinase inhibitors.

Marine biological macromolecules as matrix material for biosensor fabrication.

The ocean covers two-third of our planet and has great biological heterogeneity. Marine organisms like algae, vertebrates, invertebrates, and microbes are known to provide many natural products with biological activities as well as potential sources of biomaterials for therapeutic, biomedical, biosensors, and climate stabilization. Over the years, the field of biosensors has gained huge attention due to their extraordinary ability to provide early disease diagnosis, rapid detection of various molecules and substances along with long-term monitoring. This review aims to focus on the properties and employment of various biomaterials (carbohydrate polymers, proteins, polyacids, etc.) of marine origins such as alginate, chitin, chitosan, fucoidan, carrageenan, chondroitin sulfate, hyaluronic acid, collagen, marine pigments, marine nanoparticles, hydroxyapatite, biosilica, lectins, and marine whole cell in the design and development of biosensors. Furthermore, this review also covers the source of such marine biomaterials and their promising evolution in the fabrication of biosensors that are potent to be employed in the biomedical, environmental science, and agricultural sciences domains. The use of such fabricated biosensors harnesses the system with excellent specificity, selectivity, biocompatibility, thermal stability, and minimal cost advantages.

Effect of silicon application with mycorrhizal inoculation on Brassica juncea cultivated under water stress.

Brassica juncea L. is a significant member of the Brassicaceae family, also known as Indian mustard. Water is a limiting factor in the successful production of this crop. Here, we tested the effect of water shortage in B. juncea plants supplemented with or without the application of silicon and arbuscular mycorrhizal fungi in total 8 different treatments compared under open filed conditions using a randomised complete block design (RCBD). The treatments under control conditions were control (C, T1); C+Silicon (Si, T2); C+My (Mycorrhiza; T3); and C+Si+My (T4). In contrast, treatments under stress conditions were S (Stress; T5); S+Si (T6); S+My (T7) and S+Si+My (T8), respectively. In total, we evaluated 16 traits, including plant response to stress by evaluating peroxidase (POD), superoxide dismutase (SOD), and catalase (CAT) activity. The fresh weight (g) increased only 7.47 percent with mycorrhiza (C+My) and 22.39 percent with silicon (C+Si) but increased 291.08 percent with both mycorrhiza and silicon (C+Si+My). Using mycorrhiza (S+My) or silicon (S+Si) alone produced a significant increase of 53.16 percent and 55.84 percent in fresh weight, respectively, while using both mycorrhiza and silicon (S+Si+My) together produced a dramatic increase of 380.71 percent under stress conditions. Superoxidase dismutase concentration (Ug-1 FW) was found to be increased by 29.48 percent, 6.71 percent, and 22.63 percent after applying C+My, C+Si and C+Si+My, but treatment under stress revealed some contrasting trends, with an increase of 11.21 percent and 19.77 percent for S+My, S+Si+My, but a decrease of 13.15 percent for S+Si. Finally, in the presence of stress, carotenoid content (mg/g FW) increased by 58.06 percent, 54.83 percent, 183.87 percent with C+My, and 23.81 percent with S+My and S+Si+My, but decreased by 22.22 percent with S+Si. Silicon application proved to be more effective than AMF treatment with Rhizophagus irregularis, and the best results were obtained with the combination of Si and AMF. This work will help to suggest the measures to overcome the water stress in B. juncea.

Virtual screening of phytochemicals from Indian medicinal plants against the endonuclease domain of SFTS virus L polymerase.

Severe fever with thrombocytopenia syndrome virus (SFTSV) causes a highly infectious disease with reported mortality in the range 2.8% to 47%. The replication and transcription of the SFTSV genome is performed by L polymerase, which has both an RNA dependent RNA polymerase domain and an N-terminal endonuclease (endoN) domain. Due to its crucial role in the cap-snatching mechanism required for initiation of viral RNA transcription, the endoN domain is an ideal antiviral drug target. In this virtual screening study for the identification of potential inhibitors of the endoN domain of SFTSV L polymerase, we have used molecular docking and molecular dynamics (MD) simulation to explore the natural product space of 14 011 phytochemicals from Indian medicinal plants. After generating a heterogeneous ensemble of endoN domain structures reflecting conformational diversity of the corresponding active site using MD simulations, ensemble docking of the phytochemicals was performed against the endoN domain structures. Apart from the ligand binding energy from docking, our virtual screening workflow imposes additional filters such as drug-likeness, non-covalent interactions with key active site residues, toxicity and chemical similarity with other hits, to identify top 5 potential phytochemical inhibitors of endoN domain of SFTSV L polymerase. Further, the stability of the protein-ligand docked complexes for the top 5 potential inhibitors was analyzed using MD simulations. The potential phytochemical inhibitors, predicted in this study using contemporary computational methods, are expected to serve as lead molecules in future experimental studies towards development of antiviral drugs against SFTSV.

Comparative transcriptome profiling of high and low oil yielding Santalum album L.

East Indian Sandalwood (Santalum album L.) is highly valued for its heartwood and its oil. There have been no efforts to comparative study of high and low oil yielding genetically identical sandalwood trees grown in similar climatic condition. Thus we intend to study a genome wide transcriptome analysis to identify the corresponding genes involved in high oil biosynthesis in S. album. In this study, 15 years old S. album (SaSHc and SaSLc) genotypes were targeted for analysis to understand the contribution of genetic background on high oil biosynthesis in S. album. A total of 28,959187 and 25,598869 raw PE reads were generated by the Illumina sequencing. 2.12 million and 1.811 million coding sequences were obtained in respective accessions. Based on the GO terms, functional classification of the CDS 21262, & 18113 were assigned into 26 functional groups of three GO categories; (4,168; 3,641) for biological process (5,758;4,971) cellular component and (5,108;4,441) for molecular functions. Total 41,900 and 36,571 genes were functionally annotated and KEGG pathways of the DEGs resulted 213 metabolic pathways. In this, 14 pathways were involved in secondary metabolites biosynthesis pathway in S. album. Among 237 cytochrome families, nine groups of cytochromes were participated in high oil biosynthesis. 16,665 differentially expressed genes were commonly detected in both the accessions (SaHc and SaSLc). The results showed that 784 genes were upregulated and 339 genes were downregulated in SaHc whilst 635 upregulated 299 downregulated in SaSLc S. album. RNA-Seq results were further validated by quantitative RT-PCR. Maximum Blast hits were found to be against Vitis vinifera. From this study, we have identified additional number of cytochrome family in high oil yielding sandalwood accessions (SaHc). The accessibility of a RNA-Seq for high oil yielding sandalwood accessions will have broader associations for the conservation and selection of superior elite samples/populations for further genetic improvement program.

Natural Boron and 10B-Enriched Hexagonal Boron Nitride for High-Sensitivity Self-Biased Metal-Semiconductor-Metal Neutron Detectors.

Metal-semiconductor-metal (MSM) detectors based on Ti/Au and Ni/Au interdigitated structures were fabricated using 2.5 micrometer thick hexagonal boron nitride (h-BN) layer with both natural and 10B-enriched boron. Current-voltage (I-V) and current-time (I-t) curves of the fabricated detectors were recorded with (I N) and without (I d) neutron irradiation, allowing the determination of their sensitivity (S = (I N - I d)/I d = ΔI/I d). Natural and 10B-enriched h-BN detectors exhibited high neutron sensitivities of 233 and 367% at 0 V bias under a flux of 3 × 104 n/cm2/s, respectively. An imbalance in the distribution of filled traps between the two electric contacts could explain the self-biased operation of the MSM detectors. Neutron sensitivity is further enhanced with electrical biasing, reaching 316 and 1192% at 200 V and a flux of 3 × 104 n/cm2/s for natural and 10B-enriched h-BN detectors, respectively, with dark current as low as 2.5 pA at 200 V. The increased performance under bias has been attributed to a gain mechanism based on neutron-induced charge carrier trapping at the semiconductor/metal interface. The response of the MSM detectors under thermal neutron flux and bias voltages was linear. These results clearly indicate that the thin-film monocrystal BN MSM neutron detectors can be optimized to operate sensitively with the absence of external bias and generate stronger signal detection using 10B-enriched boron.

Self-reported survey on infection prevention and control structures in healthcare facilities part of a national level healthcare associated infection surveillance network in India, 2019.

BACKGROUND: Healthcare associated infections (HAIs) are prevalent and difficult to treat worldwide. Most HAIs can be prevented by effective implementation of Infection Prevention and Control (IPC) measures. A survey was conducted to assess the existing IPC practices across a network of Indian Hospitals using the World Health Organization designed self-assessment IPC Assessment Framework (IPCAF) tool. METHODS: This was a cross sectional observation study. Thirty-two tertiary care public and private facilities, part of the existing Indian HAI surveillance network was included. Data collected was analyzed by a central team at All India Institute of Medical Sciences, New Delhi, a tertiary care hospital of India. The WHO questionnaire tool was used to understand the capacity and efforts to implement IPC practices across the network. RESULTS: The overall median score of IPCAF across the network was 620. Based on the final IPCAF score of the facilities; 13% hospitals had basic IPC practices, 28% hospitals had intermediate and 59% hospitals had advanced IPC practices. The component multimodal strategies had the broadest range of score while the component IPC guidelines had the narrowest one. CONCLUSIONS: Quality improvement training for IPC nurses and healthcare professionals are needed to be provided to health facilities.

Structural differences in the FAD-binding pockets and lid loops of mammalian CRY1 and CRY2 for isoform-selective regulation.

The circadian clock is a biological timekeeper that operates through transcription-translation feedback loops in mammals. Cryptochrome 1 (CRY1) and Cryptochrome 2 (CRY2) are highly conserved core clock components having redundant and distinct functions. We recently identified the CRY1- and CRY2-selective compounds KL101 and TH301, respectively, which provide useful tools for the exploration of isoform-selective CRY regulation. However, intrinsic differences in the compound-binding FAD (flavin adenine dinucleotide) pockets between CRY1 and CRY2 are not well understood, partly because of nonoptimal properties of previously reported apo form structures in this particular region constituted by almost identical sequences. Here, we show unliganded CRY1 and CRY2 crystal structures with well-defined electron densities that are largely free of crystal contacts at the FAD pocket and nearby lid loop. We revealed conformational isomerism in key residues. In particular, CRY1 W399 and corresponding CRY2 W417 in the FAD pocket had distinct conformations ("out" for CRY1 and "in" for CRY2) by interacting with the lid loop residues CRY1 Q407 and CRY2 F424, respectively, resulting in different overall lid loop structures. Molecular dynamics simulations supported that these conformations were energetically favorable to each isoform. Isoform-selective compounds KL101 and TH301 preferred intrinsic "out" and "in" conformations of the tryptophan residue in CRY1 and CRY2, respectively, while the nonselective compound KL001 fit to both conformations. Mutations of lid loop residues designed to perturb their isoform-specific interaction with the tryptophan resulted in reversed responses of CRY1 and CRY2 to KL101 and TH301. We propose that these intrinsic structural differences of CRY1 and CRY2 can be targeted for isoform-selective regulation.

Reversible modulation of circadian time with chronophotopharmacology.

The circadian clock controls daily rhythms of physiological processes. The presence of the clock mechanism throughout the body is hampering its local regulation by small molecules. A photoresponsive clock modulator would enable precise and reversible regulation of circadian rhythms using light as a bio-orthogonal external stimulus. Here we show, through judicious molecular design and state-of-the-art photopharmacological tools, the development of a visible light-responsive inhibitor of casein kinase I (CKI) that controls the period and phase of cellular and tissue circadian rhythms in a reversible manner. The dark isomer of photoswitchable inhibitor 9 exhibits almost identical affinity towards the CKIα and CKIδ isoforms, while upon irradiation it becomes more selective towards CKIδ, revealing the higher importance of CKIδ in the period regulation. Our studies enable long-term regulation of CKI activity in cells for multiple days and show the reversible modulation of circadian rhythms with a several hour period and phase change through chronophotopharmacology.

Experimental and theoretical approach to probe the aquatic speciation of transuranic (neptunyl) ion in presence of two omnipresent organic moieties.

Pyrazines are omnipresent in nature and have their occurrence in plants, microbes, food supplies, marine arenas. The present studies aimed at aquatic speciation of the neptunyl ion (NpO2+) with two pyrazine compounds namely pyrazine monocarboxylic acid (PMC) and pyrazine dicarboxylic acid (PDC). Absorption spectrophotometry was used to probe the stability, speciation and spectral properties for the complexation process. NpO2+ forms a more stable complex with PMC than PDC for 1:1 (ML), while for 1:2 (ML2) the opposite trend is observed. The extent of shift in λmax, which is also an indicator for the strength of complexation, reflected similar trends for the complexation process. Isothermal titration calorimetry was employed to determine the enthalpies of complex formation, which is found to be endothermic. The complexation process is entropy driven. Linear free energy correlations were established to retrieve the coordination modes of the complexes. The variation in peak potentials (the cyclic voltammograms) with change in pH and metal to ligand ratio were explored to understand redox speciation, electron transfer kinetics and Eh-pH characteristics for the interaction of NpO2+ with pyrazine carboxylate ligands. Density functional theory calculations were employed to optimize the geometries and to calculate the bond distances and partial charges on key atoms of the optimized geometries. The theoretical calculations helped to reveal the contributions from two different configurations of the same geometry towards the optical absorption. The bond distances and partial charges estimated theoretically helped to understand the aqueous interactions at the molecular level.

Towards P-Type Conduction in Hexagonal Boron Nitride: Doping Study and Electrical Measurements Analysis of hBN/AlGaN Heterojunctions.

Reliable p-doped hexagonal boron nitride (h-BN) could enable wide bandgap optoelectronic devices such as deep ultra-violet light emitting diodes (UV LEDs), solar blind photodiodes and neutron detectors. We report the study of Mg in h-BN layers as well as Mg h-BN/AlGaN heterostructures. Mg incorporation in h-BN was studied under different biscyclopentadienyl-magnesium (Cp2Mg) molar flow rates. 2θ-ω x-ray diffraction scans clearly evidence a single peak, corresponding to the (002) reflection plane of h-BN with a full-width half maximum increasing with Mg incorporation in h-BN. For a large range of Cp2Mg molar flow rates, the surface of Mg doped h-BN layers exhibited characteristic pleats, confirming that Mg doped h-BN remains layered. Secondary ion mass spectrometry analysis showed Mg incorporation, up to 4 × 1018 /cm3 in h-BN. Electrical conductivity of Mg h-BN increased with increased Mg-doping. Heterostructures of Mg h-BN grown on n-type Al rich AlGaN (58% Al content) were made with the intent of forming a p-n heterojunction. The I-V characteristics revealed rectifying behavior for temperatures from 123 to 423 K. Under ultraviolet illumination, photocurrent was generated, as is typical for p-n diodes. C-V measurements evidence a built-in potential of 3.89 V. These encouraging results can indicate p-type behavior, opening a pathway for a new class of wide bandgap p-type layers.

Photopharmacological Manipulation of Mammalian CRY1 for Regulation of the Circadian Clock.

CRY1 and CRY2 proteins are highly conserved components of the circadian clock that controls daily physiological rhythms. Disruption of CRY functions are related to many diseases, including circadian sleep phase disorder. Development of isoform-selective and spatiotemporally controllable tools will facilitate the understanding of shared and distinct functions of CRY1 and CRY2. Here, we developed CRY1-selective compounds that enable light-dependent manipulation of the circadian clock. From phenotypic chemical screening in human cells, we identified benzophenone derivatives that lengthened the circadian period. These compounds selectively interacted with the CRY1 photolyase homology region, resulting in activation of CRY1 but not CRY2. The benzophenone moiety rearranged a CRY1 region called the "lid loop" located outside of the compound-binding pocket and formed a unique interaction with Phe409 in the lid loop. Manipulation of this key interaction was achieved by rationally designed replacement of the benzophenone with a switchable azobenzene moiety whose cis-trans isomerization can be controlled by light. The metastable cis form exhibited sufficiently high half-life in aqueous solutions and structurally mimicked the benzophenone unit, enabling reversible period regulation over days by cellular irradiation with visible light. This study revealed an unprecedented role of the lid loop in CRY-compound interaction and paves the way for spatiotemporal regulation of CRY1 activity by photopharmacology for molecular understanding of CRY1-dependent functions in health and disease.