Quantitative characterization of fluorine-centered noncovalent interactions in crystalline benzanilides.

Six isomeric molecules, featuring a minimum of three fluorine atoms on either the benzoyl or aniline side, have been synthesized, crystallized and characterized through single crystal X-ray diffraction (SCXRD). In addition, two other compounds, containing six fluorine atoms, three on each of the benzoyl and aniline side of the benzanilide scaffold have also been characterized through SCXRD. This current study aims to augment the capacity for hydrogen bond formation, specifically involving organic fluorine, by elevating the acidity of the involved hydrogens through the incorporation of highly electronegative fluorine atoms, in the presence of strong N-H×××O=C H-bonds. Lattice energy calculations and assessment of intermolecular interaction energies elucidate the contributions of electrostatics and dispersion forces in crystal packing. The topological analysis of the electron density is characterized by the presence of bond critical points (BCPs) involving C-H×××F and F×××F contacts, thus establishing the bonding nature of these interactions which play a crucial role in the crystal packing in addition to the presence of traditional N-H×××O=C H-bonds.

A novel pH-sensitive method for the quantification of Ca2+ ions by complexometric titration with Na3HEDTA.

A simple and accurate complexometric titration has been developed by the reaction between Ca2+ ions (pH 7) and Na3HEDTA (pH 11) solutions. Formation of a Ca-EDTA complex and release of H+ ions in the system were traced by a decrease in the pH. At the equivalence point of the titration, a sharp increase in the pH was observed. Looking at the working pH range (pH 6.2-7.5) of this method, another complexometric titration method has been developed by using bromothymol blue as a pH sensitive indicator. This is the first report of a complexometric titration by using an acid base indicator.

A novel syphilis Treponema pallidum lipoprotein peptide antigen diagnostic assay using red cell kodecytes in routine blood centre column agglutination testing platforms.

BACKGROUND AND OBJECTIVES: The detection of treponemal antibodies, which are used to make a diagnosis of syphilis, is important both for diagnostic purposes and as a mandatory blood donor test in most countries. We evaluated the feasibility of using Kode Technology to make syphilis peptide red cell kodecytes for use in column agglutination serologic platforms. MATERIALS AND METHODS: Candidate Kode Technology function-spacer-lipid (FSL) constructs were made for the Treponema pallidum lipoprotein (TmpA) of T. pallidum, using the peptide and FSL selection algorithms, and then used to make kodecytes. Developmental kodecytes were evaluated against a large range of syphilis antibody reactive and non-reactive samples in column agglutination platforms and compared against established methodologies. Overall, 150 reactive and 2072 non-reactive Syphicheck assay (a modified T. pallidum particle agglutination) blood donor samples were used to evaluate the agreement rate of the developed kodecyte assay. RESULTS: From three FSL-peptide candidate constructs, one was found to be the most suitable for diagnostics. Of 150 Syphicheck assay reactive samples, 146 were TmpA-kodecyte reactive (97.3% agreement), compared with 58.0% with the rapid plasmin reagin (RPR) assay for the same samples. Against the 2072 expected syphilis non-reactive samples the agreement rate for TmpA-kodecytes was 98.8%. CONCLUSION: TmpA-kodecytes are viable for use as cost-effective serologic reagent red cells for the detection of treponemal antibodies to diagnose syphilis with a high level of specificity in blood centres. This kodecyte methodology also potentially allows for introduction of the reverse-algorithm testing into low-volume laboratories, by utilizing existing transfusion laboratory infrastructure.

One-Step Catalyst-Transfer Macrocyclization: Expanding the Chemical Space of Azaparacyclophanes.

In this paper, we report on a one-step catalyst-transfer macrocyclization (CTM) reaction, based on the Pd-catalyzed Buchwald-Hartwig cross-coupling reaction, selectively affording only cyclic structures. This route offers a versatile and efficient approach to synthesize aza[1n]paracyclophanes (APCs) featuring diverse functionalities and lumens. The method operates at mild reaction temperatures (40 °C) and short reaction times (∼2 h), delivering excellent isolated yields (>75% macrocycles) and up to 30% of a 6-membered cyclophane, all under nonhigh-dilution concentrations (35-350 mM). Structural insights into APCs reveal variations in product distribution based on different endocyclic substituents, with steric properties of exocyclic substituents having minimal influence on the macrocyclization. Aryl-type endocyclic substituents predominantly yield 6-membered macrocycles, while polycyclic aromatic units such as fluorene and carbazole favor 4-membered species. Experimental and computational studies support a proposed mechanism of ring-walking catalyst transfer that promotes the macrocycle formation. It has been found that the macrocyclization is driven by the formation of cyclic conformers during the oligomerization step favoring an intramolecular C-N bond formation that, depending on the cycle size, hinges on either preorganization effect or kinetic increase of the reductive elimination step or a combination of the two. The CTM process exhibits a "living" behavior, facilitating sequential synthesis of other macrocycles by introducing relevant monomers, thus providing a practical synthetic platform for chemical libraries. Notably, CTM operates both under diluted and concentrated regimes, offering scalability potential, unlike typical macrocyclization reactions usually operating in the 0.1-1 mM range.

A nine-ring fused terrylene diimide exhibits switching between red TADF and near-IR room temperature phosphorescence.

Herein, we report the first example of a terrylene diimide derivative that switches emission between thermally activated delayed fluorescence (TADF) and room temperature phosphorescence (RTP) in the red region. By design, the molecule TDI-cDBT boasts a symmetrical, consecutively fused nine-ring motif with a kite-like structure. The rigid core formed by the annulated dibenzothiophene moiety favoured efficient intersystem crossing and yielded a narrow-band emission with a full-width half maxima (FWHM) of 0.09 eV, along with high colour purity. A small ΔE S1-T1 of 0.04 eV facilitated thermally activated delayed fluorescence, enhancing the quantum yield to 88% in the red region. Additionally, it also prefers a direct triplet emission from the aggregated state. The room temperature phosphorescence observed from the aggregates has a longer emission lifetime of 1.8 ms, which is further prolonged to 8 ms at 77 K in the NIR region. Thus, the current strategy is successful in not only reducing ΔE S1-T1 to favour TADF but also serves as a novel platform that can switch emission from TADF to RTP depending upon the concentration.

A thiolated copper-hydride nanocluster with chloride bridging as a catalyst for carbonylative C-N coupling of aryl amines under mild conditions: a combined experimental and theoretical study.

Atomically precise copper nanoclusters (Cu NCs), an emerging class of nanomaterials, have garnered significant attention owing to their versatile core-shell architecture and their potential applications in catalytic reactions. In this study, we present a straightforward synthesis strategy for [Cu29(StBu)12(PPh3)4Cl6H10][BF4] (Cu29) NCs and explore their catalytic activity in the carbonylative C-N coupling reaction involving aromatic amines and N-heteroarenes with dialkyl azodicarboxylates. Through a combination of experimental investigations and density functional theory studies, we elucidate the radical mechanisms at play. The crucial step in the catalytic process is identified as the decomposition of diisopropyl azodicarboxylates on the surface of Cu29 NCs, leading to the generation of oxyacyl radicals and the liberation of nitrogen gas. Subsequently, an oxyacyl radical abstracts a hydrogen atom from aniline, initiating the formation of an aminyl radical. Finally, the aminyl radical reacts with another oxyacyl radical, culminating in the synthesis of the desired carbamate product. This detailed analysis provides insights into the intricate catalytic pathways of Cu29 NCs, shedding light on their potential for catalyzing carbonylative C-N coupling reactions.

Modulation of Singlet-Triplet Gap in Atomically Precise Silver Cluster-Assembled Material.

Silver cluster-based solids have garnered considerable attention owing to their tunable luminescence behavior. While surface modification has enabled the construction of stable silver clusters, controlling interactions among clusters at the molecular level has been challenging due to their tendency to aggregate. Judicious choice of stabilizing ligands becomes pivotal in crafting a desired assembly. However, detailed photophysical behavior as a function of their cluster packing remained unexplored. Here, we modulate the packing pattern of Ag12 clusters by varying the nitrogen-based ligand. CAM-1 formed through coordination of the tritopic linker molecule and NC-1 with monodentate pyridine ligand; established via non-covalent interactions. Both the assemblies show ligand-to-metal-metal charge transfer (LMMCT) based cluster-centered emission band(s). Temperature-dependent photoluminescence spectra exhibit blue shifts at higher temperatures, which is attributed to the extent of the thermal reverse population of the S1 state from the closely spaced T1 state. The difference in the energy gap (ΔEST ) dictated by their assemblies played a pivotal role in the way that Ag12 cluster assembly in CAM-1 manifests a wider ΔEST and thus requires higher temperatures for reverse intersystem crossing (RISC) than assembly of NC-1. Such assembly-defined photoluminescence properties underscore the potential toolkit to design new cluster- assemblies with tailored optoelectronic properties.

Luminescent [CO2@Ag20(SAdm)10(CF3COO)10(DMA)2] nanocluster: synthetic strategy and its implication towards white light emission.

Owing to the quantized size and associated discrete energy levels, atomically precise silver nanoclusters (Ag NCs) hold great potential for designing functional luminescent materials. However, the thermally activated non-radiative transition of Ag(I)-based NCs has faded the opportunities. To acquire the structurally rigid architecture of cluster nodes for constraining such transitions, a new synthetic approach is unveiled here that utilizes a neutral template as a cluster-directing agent to assemble twenty Ag(I) atoms that ensure the maximum number of surface-protecting ligand attachment possibilities in a particular solvent medium. The solvent polarity triggers the precise structural design to circumvent the over-reliance of the templates, which results in the formation of [CO2@Ag20(SAdm)10(CF3COO)10(DMA)2] NC (where SAdm = 1-adamantanethiolate and DMA = N,N-dimethylacetamide) exhibiting an unprecedented room-temperature photoluminescence emission. The high quantum yield of the generated blue emission ensures its candidature as an ideal donor for artificial light-harvesting system design, and it is utilized with the two-step sequential energy transfer process, which finally results in the generation of ideal white light. For implementing perfect white light emission, the required chromophores in the green and red emission regions were chosen based on their effective spectral overlap with the donor components. Due to their favorable energy-level distribution, excited state energy transfers occurred from the NC to ß-carotene at the initial step, then from the conjugate of the NC and ß-carotene to another chromophore, Nile Blue, at the second step via a sequential Förster resonance energy transfer pathway.

Ultrasensitive colorimetric detection of fluoride and arsenate in water and mammalian cells using recyclable metal oxacalixarene probe: a lateral flow assay.

Globally 3 billion people are consuming water with moderately high concentrations of fluoride and arsenic. The development of a simple point of care (PoC) device or home device for the detection of fluoride/arsenic ensures safety before consuming water. Till date, lateral flow assay (LFA) based PoC devices can detect nucleic acids, viruses and diseases. An aluminium complex of rhodamine B functionalized oxacalix[4]arene (L) was designed to execute the LFA-based PoC device. Initially, Al3+ and Fe3+ ions were involved in complexation with the rhodamine B functionalized oxacalix[4]arene (L), resulting C1 (L-Al3+) and C2 (L-Fe3+) complexes respectively. The receptor L, as well as the probes (C1, C2), were characterized thoroughly using mass spectroscopy, FTIR, NMR, and EA. C1 and C2 were further utilized as recyclable probes for the detection of aqueous fluoride (21 ppb) and arsenate (1.92 ppb) respectively. The computational calculation indicates that upon complexation, the spirolactam ring opening at the rhodamine B site leads to optoelectronic changes. The consistency of LFA-based portable sensing device has been tested with water samples, synthetic fluoride standards and dental care products like toothpaste and mouthwash with concentrations ≥ 3 ppm. Moreover, fixed cell imaging experiments were performed to ascertain the in-vitro sensing phenomena.

Direct Arylation of Distal and Proximal C(sp3)-H Bonds of t-Amines with Aryl Diazonium Tetrafluoroborates via Photoredox Catalysis.

A visible light-mediated arylation protocol for t-amines has been reported through the coupling of γ- and α-amino alkyl radicals with different aryl diazonium salts using Ru(bpy)3Cl2·6H2O as a photocatalyst. Structurally different 9-aryl-9,10-dihydroacridine, 1-aryl tetrahydroisoquinoline, hexahydropyrrolo[2,1-a]isoquinoline, and hexahydro-2H-pyrido[2,1-a]isoquinoline frameworks with different substitution patterns have been synthesized in good yield using this methodology.

p-Silylation of Arenes via Organic Photoredox Catalysis: Use of p-Silylated Arenes for Exclusive o-Silylation, o-Acylation, and o-Alkylation Reactions.

Photocatalytic regiospecific p-silylation of arenes has been achieved by the coupling of in situ generated silyl radical with arene radical cation. The strategy involves reductive activation of PhSe-SiR3 and single electron transfer from the electron rich arene to 9,10-dimethoxyanthracene radical cation (DMA•+). p-Silyl arenes, thus formed, are further utilized for exclusive o-silylation reaction and for regiospecific o-acylation as well as o-alkylation reaction.

Demographics, Pattern of Care, and Outcome Analysis of Malignant Melanomas - Experience From a Tertiary Cancer Centre in India.

BACKGROUND: Treatment of malignant melanoma has undergone a paradigm shift with the advent of immune checkpoint inhibitors (ICI) and targeted therapies. However, access to ICI is limited in low-middle income countries (LMICs). PATIENTS AND METHODS: Histologically confirmed malignant melanoma cases registered from 2013 to 2019 were analysed for pattern of care, safety, and efficacy of systemic therapies (ST). RESULTS: There were 659 patients with a median age of 53 (range 44-63) years; 58.9% were males; 55.2% were mucosal melanomas. Most common primary sites were extremities (36.6%) and anorectum (31.4%). Nearly 10.8% of the metastatic cohort were BRAF mutated. Among 368 non-metastatic patients (172 prior treated, 185 de novo, and 11 unresectable), with a median follow-up of 26 months (0-83 months), median EFS and OS were 29.5 (95% CI: 22-40) and 33.3 (95% CI: 29.5-41.2) months, respectively. In the metastatic cohort, with a median follow up of 24 (0-85) months, the median EFS for BSC was 3.1 (95% CI 1.9-4.8) months versus 3.98 (95% CI 3.2-4.7) months with any ST (HR: 0.69, 95% CI: 0.52-0.92; P = 0.011). The median OS was 3.9 (95% CI 3.3-6.4) months for BSC alone versus 12.0 (95% CI 10.5-15.1) months in any ST (HR: 0.38, 95% CI: 0.28-0.50; P < 0.001). The disease control rate was 51.55%. Commonest grade 3-4 toxicity was anemia with chemotherapy (9.5%) and ICI (8.8%). In multivariate analysis, any ST received had a better prognostic impact in the metastatic cohort. CONCLUSIONS: Large real-world data reflects the treatment patterns adopted in LMIC for melanomas and poor access to expensive, standard of care therapies. Other systemic therapies provide meaningful clinical benefit and are worth exploring especially when the standard therapies are challenging to administer.

Cocrystals, Salts, and Salt-Solvates of olanzapine; selection of coformers and improved solubility.

Pharmaceutical cocrystals and salts are extensively researched in recent years due to their ability to tune the physicochemical properties of active pharmaceutical ingredients (APIs). A model API, olanzapine, an atypical antipsychotic drug classified as Biopharmaceutical Classification System class II, is used in this study. Cocrystals and salts of olanzapine are discovered using solvent drop grinding and ball milling. Appropriate coformers were selected based on a combination of hydrogen-bond propensity (HBP) and hydrogen-bond coordination (HBC) calculations. Eight new multicomponent phases of olanzapine, including one cocrystal hydrate with phenol; four anhydrous salts with salicylic acid, terephthalic acid, anthranilic acid, 3-hydroxybenzoic acid, and 2-aminoterephthalic acid; one salt dihydrate with terephthalic acid; and one salt solvate with 3-hydroxybenzoic acid and acetonitrile, have been discovered and characterized by PXRD and DSC. One reported cocrystal (olanzapine-resorcinol) has also been considered for the dissolution test. All these newly formed solid phases followed the "ΔpKa rule of 3". The crystal structures of cocrystal/salts were determined by single-crystal X-ray (sc-XRD) diffraction. With the collected single-crystal data, the crystal packings were found to be primarily stabilized via strong hydrogen bonds between carboxyl, phenolic hydroxyl of co-formers/salt-formers with the piperazine and diazepine nitrogen of olanzapine, which confirmed the predicted result from the HBP and HBC calculations. HPLC coupled with UV-vis detector was used in the solubility and dissolution test instead of UV-vis spectroscopy, to avoid the peak overlap between olanzapine and co-formers/salt-formers. A threefold increase in the solubility was observed in olanzapinium 3-hydroxybenzoate and olanzapinium anthranilate, and an almost fivefold increase in solubility of olanzapinium 2-aminoterephthalate.

Prins cyclization-mediated stereoselective synthesis of tetrahydropyrans and dihydropyrans: an inspection of twenty years.

Functionalized tetrahydropyran (THP) rings are important building blocks and ubiquitous scaffolds in many natural products and active pharmaceutical ingredients (API). Among various established methods, the Prins reaction has emerged as a powerful technique in the stereoselective synthesis of the tetrahydropyran skeleton with various substituents, and the strategy has further been successfully applied in the total synthesis of bioactive macrocycles and related natural products. In this context, hundreds of valuable contributions have already been made in this area, and the present review is intended to provide the systematic assortment of diverse Prins cyclization strategies, covering the literature reports of the last twenty years (from 2000 to 2019), with an aim to give an overview on exciting advancements in this area and designing new strategies for the total synthesis of related natural products.

An oxacalix[4]arene derived dual sensing fluorescent probe for the detection of As(v) and Cr(vi) oxyanions in aqueous media.

An oxacalix[4]arene-Ce(iii) complex viz. L-Ce(III) has been introduced for the selective detection of As(v) and Cr(vi) oxyanions in aqueous medium. The binding mode of L-Ce(III) + AsO43-/CrO42- was completely investigated with fluorometric titration, time resolve fluorescent decay and FTIR analyses. Photoinduced electron transfer (PET) and chelation-enhanced fluorescence (CHEF) play an important role in the sensing of these oxyanions. The characteristic fluorescence of the L-Ce(III) complex has been quenched by AsO43- and CrO42- through cascading the ligating sites. Cyclic voltammetry (CV) experiments with various scan rates suggest that the electrochemical processes on the electrodes were controlled by diffusion. Both the analytes exhibit a lower limit of detection (LOD) below their standard EPA permissible limits. Moreover, the probe successfully detects the oxyanions in environmental real samples with excellent recovery ranging from 97 to 101%.

Crystal structure analysis of the biologically active drug mol-ecule riluzole and riluzolium chloride.

This study is an investigation into the crystal structure of the biologically active drug mol-ecule riluzole [RZ, 6-(tri-fluoro-meth-oxy)-1,3-benzo-thia-zol-2-amine], C8H5F3N2OS, and its derivative, the riluzolium chloride salt [RZHCl, 2-amino-6-(tri-fluoro-meth-oxy)-1,3-benzo-thia-zol-3-ium chloride], C8H6F3N2OS+·Cl-. In spite of repeated efforts to crystallize the drug, its crystal structure has not been reported to date, hence the current study provides a method for obtaining crystals of both riluzole and its corresponding salt, riluzolium hydro-chloride. The salt was obtained by grinding HCl with the drug and crystallizing the obtained solid from di-chloro-methane. The crystals of riluzole were obtained in the presence of l-glutamic acid and d-glutamic acid in separate experiments. In the crystal structure of RZHCl, the -OCF3 moiety is perpendicular to the mol-ecular plane containing the riluzolium ion, as can be seen by the torsion angle of 107.4 (3)°. In the case of riluzole, the torsion angles of the four different mol-ecules in the asymmetric unit show that in three cases the tri-fluoro-meth-oxy group is perpendicular to the riluzole mol-ecular plane and only in one mol-ecule does the -OCF3 group lie in the same mol-ecular plane. The crystal structure of riluzole primarily consists of strong N-H⋯N hydrogen bonds along with weak C-H⋯F, C-H⋯S, F⋯F, C⋯C and C⋯S inter-actions, while that of its salt is stabilized by strong [N-H]+⋯Cl- and weak C-H⋯Cl-, N-H⋯S, C-H⋯F, C⋯C, S⋯N and S⋯Cl- inter-actions.

Heterocyclization involving benzylic C(sp3)-H functionalization enabled by visible light photoredox catalysis.

A general and efficient method for heterocyclization involving benzylic C(sp3)-H functionalization enabled by visible light photoredox catalysis to access a wide range of structurally diverse oxygen as well as nitrogen heterocycles up to a gram scale is reported. The potential application of this new methodology is demonstrated by the total synthesis of (-)-codonopsinine and (+)-centrolobine. Herein it is proposed that selectfluor, unlike a fluorinating reagent, acts as an oxidative quencher and a hydrogen radical acceptor.

Metal-free Annulation at the Ortho- and Bay-Positions of Perylene Bisimide Leading to Lateral π-Extension with Strong NIR Absorption.

A novel ortho/ bay annulation reaction of perylene bisimide (PBI) has been explored in a single step synthetic procedure using perylene bisimide 1 and 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) in the absence of any metal catalyst. The single crystal solid-state X-ray diffraction structure showed a distorted framework of DBU-fused PBI 2. Compound 2 exhibited intense near-infrared absorption up to 950 nm. Reversible protonation and deprotonation accompany drastic changes in the photophysical characteristics. Further, the reaction of perylene biscarboxyanhydride with DBU offered a caprolactam ring-substituted perylene bisimide 3.

Larvicidal study of tetrahydropyrimidine scaffolds against Anopheles arabiensis and structural insight by single crystal X-ray studies.

A series of methyl or ethyl 4-(substitutedphenyl/pyridyl)-6-methyl-2-oxo/thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate (HPM) analogues 4a-g were synthesized and evaluated for larvicidal activity against Anopheles arabiensis. These newly synthesized compounds were characterized by spectral studies such as FT-IR, NMR (1 H and 13 C), LC-MS, and elemental analysis. The conformational features and supramolecular assembly of molecules 4a, 4b, and 4e were further analyzed from single crystal X-ray study. The larvicidal activity of these tetrahydropyrimidine pharmacophore series was analyzed based on their relative substituents. Among the synthesized HPM analogous from the series, compounds 4d and 4e both having electron withdrawing chlorine group on phenyl ring at the fourth position of the tetrahydropyrimidine pharmacophore exhibited the most promising larvicidal activity.

Quantitative characterization of new supramolecular synthons involving fluorine atoms in the crystal structures of di- and tetrafluorinated benzamides.

Strong hydrogen bonds play a significant role in crystal packing. In particular, the involvement of interactions involving fluorine in controlling the crystal packing requires appropriate attention, especially in the presence of other strong hydrogen bonds. In the present study, a detailed quantitative assessment has been performed of the nature, energetics and topological properties derived from the electron density in model compounds based on fluorinated benzamides (a total of 46 fluorine-substituted benzamides containing multiple fluorine atoms) in the solid state. The primary motivation in the design of such molecules is to enhance the acidity of the interacting H atoms in the presence of an increasing number of F atoms on the molecular scaffold, resulting in increased propensity towards the formation of intermolecular interactions involving organic fluorine. This exercise has resulted in the identification of new and frequently occurring supramolecular synthons involving F atoms in the packing of molecules in the solid state. The energetics associated with short and directional intermolecular Csp2-H...F-Csp2 interactions with significantly high electrostatic contributions is noteworthy, and the topological analysis reveals the bonding character of these ubiquitous interactions in crystal packing in addition to the presence of Csp2-F...F-Csp2 contacts.