Cisplatin analogue consisting of platinum(II) complexed with a cyclic selenide, trans 3,4-dihydroxy selenolane (DHSred) was synthesized. It was characterized by microanalyses, NMR (1H, 13C{1H}, 77Se{1H} and 195Pt{1H}), FT-IR, Raman and UV-Vis spectroscopy and its molecular structure was obtained by a single crystal X-ray diffraction analysis as cis-[PtCl2(DHSred)2].H2O. It was evaluated for existance of polymorphism by DSC analysis which revealed the absence of any polymorphism but it exists as a single isoform in a temperature range-25 to 80 degrees C. The cis-[PtCl2(DHSred)2].H2O was evaluated for its cytotoxicity against human cancer cell lines from skin (A431), breast (SKBR3), lung (A549) and brain (LN229) origin. It exhibited a significantly low cytotoxicity as compared with a standard aquated cisplatin as well as DHSred itself was found to be non-cytotoxic. This observation directed us to design a strategy of DHSred treatment after cisplatin chemotherapy to remove the excess of cisplatin accumulated in cells especially in renal system in order to ameliorate the severe side effects of cisplatin. To evaluate this, we have synthesized the cis-[Pt(NH3)2(DHSred)2]Cl2 complex in-situ by reacting aquated cisplatin with DHSred and this complex also exhibited very poor cytotoxicity as compared to cisplatin. It revealed, that the excess of highly toxic aquated cisplatin could be converted to a nontoxic cisplatin analogue i.e., cis-[Pt(NH3)2(DHSred)2]Cl2 which is anticipated to overcome the severe side effects, because of cisplatin accumulation. Additionally, the DFT calculations were performed to study geometrical and electronic structures to correlate these with the observed highly decreased cytotoxicity of cis-[PtCl2(DHSred)2].H2O and cis-[Pt (NH3)2(DHSred)2]Cl2 complexes in comparison with cisplatin.

Click synthesis of ether-ester linked 1,4-disubstituted 1,2,3-triazoles (7a-j) was carried out through reaction of Benzyl/phenethyl 2-bromoacetates (6a-e) and 1-(4-(prop-2-yn-1-yloxy)phenyl)ethanone (3a)/phenyl(4-(prop-2-yn-1-yloxy)phenyl)methanone (3b) and sodium azide. Further, 1,4-disubstituted 1,2,3-triazoles containing hydrazone functionality (9a-o) were synthesized from ether-ester linked 1,4-disubstituted 1,2,3-triazoles (7a-e) through condensation with phenylhydrazine derivatives (8a-c). The structural characterization of the synthesized 1,2,3-triazoles were accomplished by FTIR,1H NMR,13C NMR, HRMS techniques. The structure of compound 7e (CCDC 2130838) was also confirmed by X-ray crystallography. All the synthesized compounds were screened for antimicrobial activity against Staphylococcus aureus, Bacillus subtilis, Salmonella enterica, Escherichia coli, Candida albicans and Rhizopus oryzae. The substituted 1,2,3-triazoles reflected moderate activity against tested bacterial/fungal strains. Docking studies of the compound 9 l were also undertaken in the binding site of E. coli DNA gyrase and C. albicans Lanosterol 14-alpha-demethylase to have an insight into mode of action.

Early detection of lung cancer is crucial because of the lower survival rate for improving treatment outcomes. Chip-scale photonic biosensors offer a promising label-free and non-invasive diagnostic approach by analyzing intercellular properties. Here, we demonstrate a chip-scale photonic platform based on semiconductor heterojunctions of n-type ZnO/TiO2 with a comb-like structure to enable label-free detection of lung cancer cells. The lung cancer cells are detected using the engineered structure of the proposed photodetector through distinct fluctuations in the cells' electrical signature. The proposed voltage-controlled device configuration enhances interband transitions within the ZnO/TiO2 depletion region with strong light-matter interaction, particularly in the UV spectrum. The proposed biosensor results in an enhanced photocurrent response in the presence of A549 cells, demonstrating its high sensitivity towards lung cancer detection. The photocurrent in PBS increases from 45 μA to 80 μA when a small concentration of A549 cells (500 cells/μl) is added at a low bias of 1.6 V, demonstrating label-free detection capability. The proposed device with its engineered structure combines ZnO's efficient charge carrier transport with TiO2's proven biocompatibility, enabling sensitive and non-invasive analysis with an additional flexibility of voltage-controlled operation. The demonstrated on-chip biosensor can be a potential candidate for cancer detection, which can enable future integration with compact biosystems.

BACKGROUND:SARS-CoV-2 papain-like protease (PLpro) is essential for viral replication and immune evasion. It contains an N-terminal ubiquitin-like (Ubl) domain, whose involvement in enzymatic function remains poorly understood. RESULTS:In this study, we investigated the role of the Ubl domain in modulating the structural dynamics and catalytic efficiency of PLpro. Using molecular dynamics (MD) simulations, inhibitor binding assays, and steady-state kinetic analyses, we found that the Ubl domain stabilizes critical structural elements, notably the ridge helix in the thumb subdomain. Removal of the Ubl domain altered substrate processing, reducing catalytic efficiency of the enzyme. Interestingly, free ubiquitin enhanced enzymatic activity, likely via non-canonical binding sites distinct from the SUb1 and SUb2 sites. CONCLUSION:These findings uncover a regulatory role for the Ubl domain in allosteric modulation of PLpro activity and reveal additional layers of enzymatic plasticity. Understanding these mechanisms could guide the design of future antiviral therapeutics targeting PLpro's regulatory or allosteric sites.

The development of environmentally friendly and efficient protocol for the synthesis of heterocyclic compounds is the current demand of synthetic community. Solvent-free synthesis has emerged as a sustainable approach reducing waste generation, and minimizing environmental impact. In this connection, we have developed a solvent-free method for the construction of five membered heterocycles i.e. isoxazoline and pyrazoline from α, β-unsaturated carbonyl compounds and Hydrazine/hydroxylamine hydrochloride. This protocol involves the [3+2] cycloaddition reaction between α, β-unsaturated carbonyl compounds and hydrazine hydrochloride/hydroxylamine hydrochloride under solvent free conditions to provide the substituted isoxazoline and pyrazoline in excellent yields. The synthesized compounds were characterized through 1H NMR, 13C NMR, Mass spectral data and IR. These newly synthesized compounds were screened for their antihyperglycemic activity using sucrose loaded diabetic model. Isoxazoline derivatives offered potent antihyperglycemic response than correspondence pyrazoline derivatives. Compounds bearing isoxazoline ring II A and II E showed maximum % fall of blood glucose level than control group which was comparable to the standard drug metformin. The newer compounds VIA, VIB, and VIC also evaluated for their anti-hyperglycemic activities, compound VIC showed appreciable response (62.5% antihyperglycemic activity).

A novel copper(I) complex, [CuI(L)(CH3CN)]CF3SO3 (1) (L = 1,1,2-tri(pyridin-2-yl)propan-1-ol), has been synthesized, characterized, and investigated as a bioinspired model for copper monooxygenases. Under aerobic conditions in CH3CN, complex 1 undergoes conversion to a dicopper complex, [(CuIIL)(CuIIL H)(SO3CF3)2]·CF3SO3·H2O (2), whose molecular structure reveals a Cu-Cu distance of 2.96 Å. A dicopper(II) complex, [(LCuII)2(SO3CF3)2] (3), has been synthesized for comparison, which exhibits a similar Cu-Cu distance of 2.97 Å. EPR spectroscopy has ascertained the solution-state geometries of complexes 2 and 3, which displayed g∥ > g⊥ values, indicative of distorted square pyramidal geometries consistent with their solid-state structures. Complex 1 selectively hydroxylates benzene in the presence of O2 and Et3N, affording 7% phenol based on the substrate, without any side products. However, the use of H2O2 as the oxygen source under identical conditions significantly increases the phenol yield to 19%. The catalytically active intermediates generated by the reaction of complex 1 with dioxygen showed an O (π*σ) → Cu ligand-to-metal charge transfer (LMCT) transition at 360 nm and a d-d transition at 650 nm. These spectral features are more pronounced with H2O2, showing a new LMCT transition at 360 nm and a very weak d-d transition at 689 nm. This is supported by solution FT-IR spectroscopy, which showed an O-O stretching frequency at 890 cm-1 (DFT spectra at 829 cm-1), corresponding to a Cu-OOH intermediate. The structure of the [(L)CuII-OOH]+ species was optimized by DFT calculations. Kinetic isotope effect (KIE) studies using C6H6/C6D6 (1 : 1) (kH/kD = 1.03) and isotopic labeling experiments using H218O2 support our proposed mechanism of benzene hydroxylation. In contrast, dinuclear complexes 2 and 3 exhibited poor benzene hydroxylation activity even with H2O2 and yielded only 4% and 6% phenol, respectively, along with by-products such as biphenyl and quinone under identical conditions.

Copper sulfide nanostructures have garnered strategic importance in green energy applications due to their economic nature and impressive performances. This account presents a straightforward and scalable route to access digenite (Cu1.8S or Cu9S5) phase of copper sulfide in nano-dimension. The synthesis is facilitated through low temperature rapid thermolysis of a newly synthesized and structurally characterized single source molecular precursor, namely [Cu(Spyz-2)(PPh3)(2)]center dot MeOH (1). The crystal structure, phase purity, and morphology of the nanostructures were thoroughly examined by PXRD and electron microscopic techniques. The average crystallite size and morphology of the nanostructures were found to be the function of the different capping agents (OAm and DDT) employed for the synthesis. DRS studies on the nanomaterials revealed blue shifted optical band gap (2.09-2.13 eV) which were found to be optimum for photoelectrochemical application. A prototype photo-electrochemical cell, fabricated using the pristine nanostructures exhibit high photocurrent generation along with nice photo-switching property which pose them as suitable alternatives for green energy applications and environmental remediation.

Copper-based binary and ternary sulfides have attracted significant attention due to their excellent photophysical properties, making them highly promising for high-performance photovoltaic devices. This study focuses on the synthesis and structural characterization of an air-stable binuclear Cu-pyrazinethiolate-phosphine complex, which serves as an efficient single-source molecular precursor for the preparation of CuS nanoplatelets. Furthermore, the utility of this complex as a versatile molecular precursor for the preparation of copper-based ternary sulfides, such as CuInS2, Cu2SnS3, and CuSbS2, has been demonstrated. A plausible mechanism for the facile formation of these ternary materials is proposed based on the presence of disulfide (S-S) linkages in CuS. The crystal structure, phase purity, and compositions of the nanoparticles were confirmed using powder X-ray diffraction (PXRD), X-ray photoelectron spectroscopy (XPS), energy-dispersive X-ray spectroscopy (EDS), and area elemental mapping. Electron microscopic studies revealed the formation of a two-dimensional (2D) nanoplatelet morphology with varied shapes and sizes. Ultraviolet-visible (UV-vis) diffuse reflectance spectroscopy showed a slight blue shift in the band gap of the nanoparticles compared to their bulk counterparts, which can be attributed to quantum confinement or surface lattice distortion effects. The band gap and the pristine nanoparticles were found to be blue-shifted compared to the bulk material. Prototype photoelectrochemical cells, fabricated using pristine nanoparticles, exhibit nice photocurrent generation along with optimum photoswitching, which poses them as suitable materials for clean-energy applications.

As the global health crisis due to evolution of mutations in SARS-CoV-2 continues, it is important to develop several effective antivirals to control the disease. Targeting papain-like protease (PLpro) of SARS-CoV-2 for drug development is a promising strategy due to its dual role in promoting viral replication and dysregulating host immune responses. Here, we screened a library of compounds to find potential inhibitors of PLpro. We find aurintricarboxylic acid (ATA) inhibits PLpro with Ki and IC50 values of 16 μM and 30 μM, respectively. The binding of ATA to PLpro was further characterized using isothermal titration calorimetry, differential scanning fluorimetry, dynamic light scattering and circular dichroism spectrometry. In vitro assays showed the antiviral potential of ATA with IC50 of 50 μM. In vivo efficacy was studied in Syrian hamsters and the results are being discussed.

The COVID-19 pandemic has been driven by the emergence of SARS-CoV-2 variants with mutations across all the viral proteins. Although mutations in the spike protein have received significant attention, understanding the prevalence and potential impact of mutations in other viral proteins is essential for comprehending the evolution of SARS-CoV-2. Here, we conducted a comprehensive analysis of approximately 14 million sequences of SARS-CoV-2 deposited in the GISAID database until December 2022 to identify prevalent mutations in the non-spike proteins at the global and country levels. Additionally, we evaluated the energetics of each mutation to better understand their impact on protein stability. While the consequences of many mutations remain unclear, we discuss potential structural and functional significance of some mutations. Our study highlights the ongoing evolutionary process of SARS-CoV-2 and underscores the importance of understanding changes in non-spike proteins.

A new series of hydrazones tethered 1,4-disubstituted 1,2,3-triazoles have been synthesized from novel N-substituted alkynes derived from benzohydrazides and benzyl bromides through Cu(I) catalyzed 1,3-dipolar cycloaddition reaction. All the newly synthesized triazoles were characterized by FTIR, H-1 NMR, C-13 NMR and HRMS. Further, the structure of one of the novel alkyne N'-benzylidene-N-(prop-2-yn-1-yl)benzohydrazide has been also characterized by single X-ray crystallography (CCDC 2192009 ). The synthesized compounds were assessed for antitubercular and antimicrobial activities. Isoniazid hydrazone tethered with disubstituted 1,2,3-triazole(7s), displayed moderate antimycobacterial activity. Compound 7r exhibited apperciable inhibition against bacterial strains-S. aureus, B. subtiils, E. coli and fungal strains-C. albicans and A. niger with MIC value 0.0121 mu mol/mL as compared to standard drugs used. Further, molecular docking studies of broadly active compounds 7r and 7s in the active site of DNA gyrase and Enoyl-acp reductase (INHA) respectively were also performed to have the probable mode of action. In-silico ADME study also reflects potential of synthesized triazoles as drug agent. (c) 2023 Elsevier B.V. All rights reserved.

Alkaline phosphatases (APs), represented by E. coli AP (ECAP), employ an arginine residue to stabilize the phosphoryl group in the active site; whereas, AP from Sphingomonas (SPAP) shows a unique combination of substrate-binding residues; Thr89, Asn110, Lys171, and Arg173. Although such combination has been observed only in SPAP, these residues are present separately in different members of the AP superfamily. Here, we establish the presence of two distinct classes of APs; ECAP-type and SPAP-type. Bioinformatic analyses show that SPAP-type of APs are widely distributed in the bacterial kingdom. The role of active site residues in the catalytic mechanism has been delineated through a set of crystal structures reported here. These structures, representing different stages of the reaction pathway provide wealth of information for the catalytic mechanism. Despite critical differences in the substrate binding residues, SPAP follows a mechanism similar to that of ECAP-type of APs. Structure-based phylogenetic analysis suggests that SPAP and ECAP may have diverged very early during the evolution from a common ancestor. Moreover, it is proposed that the SPAP-type of APs are fundamental members of the AP superfamily and are more closely related to other members of the superfamily as compared to the ECAP-type of APs.

Binary cocrystals of 1,4-bis(4 ' -pyridyl)-2,3-diaza-1,3-butadiene (4,4 ' -bpdb, L-1) and 1,4-bis(3 ' -pyridyl)-2,3diaza-1,3-butadiene (3,3 ' -bpdb, L-2) in combination with two templates, resorcinol (T-1) and orcinol (T-2) were synthesized by mechanochemical dry grinding. Their structures were elucidated by single crystal Xray crystallography, powder X-ray diffraction (PXRD) and characterized by other spectroscopies, such as optical, nuclear magnetic resonance, and Fourier transform infra-red spectroscopy. Expected 2:2 cocrystals were obtained, except for the combination of L-2 and T-1 , crystals of 2L(2) :T-1 cocrystal was obtained via solution crystallization. Solid state photoluminescence of these cocrystals have been explored. (c) 2022 Elsevier B.V. All rights reserved.

The recent emergence of pandemic of coronavirus (COVID-19) caused by SARS-CoV-2 has raised significant global health concerns. More importantly, there is no specific therapeutics currently available to combat against this deadly infection. The enzyme 3-chymotrypsin-like cysteine protease (3CLpro) is known to be essential for viral life cycle as it controls the coronavirus replication. 3CLpro could be a potential drug target as established before in the case of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). In the current study, we wanted to explore the potential of fused flavonoids as 3CLpro inhibitors. Fused flavonoids (5a,10a-dihydro-11H-benzofuro[3,2-b]chromene) are unexplored for their potential bioactivities due to their low natural occurrences. Their synthetic congeners are also rare due to unavailability of general synthetic methodology. Here we designed a simple strategy to synthesize 5a,10a-dihydro-11H-benzofuro[3,2-b]chromene skeleton and it's four novel derivatives. Our structural bioinformatics study clearly shows excellent potential of the synthesized compounds in comparison to experimentally validated inhibitor N3. Moreover, in-silico ADMET study displays excellent druggability and extremely low level of toxicity of the synthesized molecules. Further, for better understanding, the molecular dynamic approach was implemented to study the change in dynamicity after the compounds bind to the protein. A detailed investigation through clustering analysis and distance calculation gave us sound comprehensive data about their molecular interaction. In summary, we anticipate that the currently synthesized molecules could not only be a potential set of inhibitors against 3CLpro but also the insights acquired from the current study would be instrumental in further developing novel natural flavonoid based anti-COVID therapeutic spectrums.

L-histidine crystallizes in three different crystal structure with nitric acid, i.e. L-histidinium nitrate, L-histidinium nitrate monohydrate and L-Histidinium dinitrate. Also there is DL-histidinium dinitrate. Though the structural aspects of histidinium nitrate monohydrate, L-Histidinium dinitrate and DL-histidinium nitrate are well studied, the structural studies on L-histidinium nitrate is not dealt in detail. Here we have tried to discuss in detail the crystal structure of L-histidinium nitrate using both single crystal X-ray and neutron diffraction. The crystal structure consists one L-histidine molecule which has the amino and imino groups protonated, but the carboxylic acid group is deprotonated. The nitrate ion is in anionic state ie NO3-. The conformation of histidine (N1-C2-C3-C4=64.99 degrees) is gauche (-). Also a comparison of the structure of L-histidinium nitrate with other three available crystal structures retrieved using CSD have been carried out. It was found that L-histidine in L-histidinium nitrate monohydrate adopts gauche (+) conformation and in other three structure it is gauche (-), and L-histidinium nitrate has the lowest volume. Hirshfeld surface and interaction energies analysis of all the above structures were carried out using the x-ray data. L-histidinium nitrate monohydrate shows maximum globuarity. Interaction energy obtained from energy framework showed that L-histidinium nitrate monohydrate has maximum total energy of -41.5(kJ/Mole). The asphericity of our structure L-histidinium nitrate is 0.252 indicating prolate nature unlike the other three complexes. The percentage of H center dot center dot center dot H contacts is maximum in L-histidinium nitrate which is 27.3%. A comparison of various contacts of histidine between the x-ray and neutron structure of ours shows that the maximum change is reflected in the C center dot center dot center dot H and H center dot center dot center dot H contacts with C center dot center dot center dot H having a higher percentage and H center dot center dot center dot H having a lower percentage in the neutron structure indicating that the neutron diffraction maps shows the hydrogen bond interaction more accurately. The three complexes, except DL Histidinium dinitrate crystallizes in a non-centrosymmetric space group and hence could exhibit second-order optical non-linear properties, attempts were made to calculate heats of formation, dipole moments (D), polarizabilities (alpha) and first hyperpolarizabilities (beta) using the semi empirical method at the PM6 level using MOPAC2009 and the packing energy as implemented in MERCURY. It was found that the average beta of L-histidinium nitrate monohydrate was the highest amongst the three showing that it is more suitable for NLO material. (C) 2022 Elsevier B.V. All rights reserved.

The title complex [PdCl(L)] (1), is obtained from the reaction of SCS pincer ligand HL (where, HL = N,N'-di-tert-butylbenzene-1,3-dicarbothioamide) with lithium tetrachloropalladate (II) in methanol. The compound 1 is characterized by elemental analysis, FTIR, 1H, and 13C-NMR spectroscopy, UV-Vis spectroscopy, powder X-ray diffraction and X-ray crystallographic techniques. At room temperature, 1 emits luminescence light of wavelength 460 nm in the solid state upon excitation by UV light of wavelength 280 nm. The average emission lifetime indicates that, both the ligand and complex emission is fluorescence in nature and involves mainly ligand centers π-π* deexcitation. It also shows good catalytic activity towards Mizoroki-Heck and Suzuki-Miyaura cross-coupling reactions of aryl bromides with tert-butyl acrylate and p-tolylboronic acid respectively. For both type of reactions, more than 99% conversion of the substrates is found to occur for electronically activated p-nitro bromobenzene using 1 mol % of 1. Further, modern DFT calculations are performed to decipher the mechanistic insight on the preferable pathways of the Mizoroki-Heck cross-coupling reaction. Stepwise free energy of reactions for various probable reaction pathways suggest that the catalytic route has profound preference for Pd(0)-Pd(II) over Pd(II)-Pd(IV) pathway.

Despite phenomenal clinical success, the efficacy of platinum anticancer drugs is often compromised due to inherent and acquired drug resistant phenotypes in cancers. To circumvent this issue, we designed two heterobimetallic platinum (II)-ferrocene hybrids that display multi-pronged anticancer action. In cancer cells, our best compound, 2, platinates DNA, produces reactive oxygen species, and has nucleus, mitochondria, and endoplasmic reticulum as potential targets. The multi-modal mechanism of action of these hybrid agents lead to non-apoptotic cell death induction which enables circumventing apoptosis resistance and significant improvement in platinum cross resistance profile. Finally, in addition to describing detail mechanistic insights, we also assessed its stability in plasma and demonstrate anticancer efficacy in an in vivo A2780 xenograft model. Strikingly, compared to oxaliplatin, our compound displays better tolerability, safety profile and efficacy in vivo.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

Synthesis and characterization of an organo-selenium compound, bis(pyrazinyl)selenide is presented which was further employed as a linker for silver(I) coordination polymer. Accordingly, it was reacted with AgBF4 to obtain its coordination polymer of composition, [Ag(pyz2Se)](BF4)·H2O. Crystallographic structure elucidation reveals that the resulting compound is a two-dimensional coordination polymer. Each silver(I) centre possesses coordination number of 5, defined by two selenium and three nitrogen donors, and it constitutes in a distorted trigonal pyramidal coordination sphere. One pyrazinyl ring bridges two Ag(I) by both of its N-atoms, while for other pyrazinyl ring, only N-atom participate in coordination. The BF4− anion present in the lattice balances the charge. In addition, there is a water molecule present in the crystal lattice. The idle N-atom, which does not take part in coordination, forms hydrogen bonding interaction with the water molecule. More interestingly, this coordination polymer can be obtained just by grinding the ingredients on a mortar, which offer a solventless green synthesis.

An air and moisture stable Pd(II) complex with a pyridyl based selenoether ligand was synthesized and characterized with microanalysis, UV-Vis and NMR spectroscopy. The molecular structure of the complex was established by single crystal XRD analysis. The complex upon thermolysis in oleyl amine (OAm) at higher temperatures about 270 degrees C afforded Pd17Se15 nanoparticles of average dimensions around 14-19 nm. Phase purity, crystal structure and morphology of nanomaterials were assessed by pXRD, EDS and electron microscopy. Growth duration of nanoparticles was found to have profound effect on the particle size of Pd17Se15 nano-particles. Time dependent studies indicate that the preparation of Pd17Se15 nanoparticles from molecular pre-cursor proceeds via the involvement of Pd nanoparticles.