Design and synthesis of triphenylamine-substituted vinyl sulphide and its derivatives for fully transparent-to-black electrochromism.

Herein, we report the design and green synthesis of stereodefined tetrasubstituted alkenes (TPA-V-S, TPA-V-SO, and TPA-V-SO2) bearing a triphenyl amine (TPA) and a sulfenyl or sulfoxide, or sulfone functional group situated in the anti-orientation and two phenyl rings anti to each other. Notably, TPA-V-S exhibited reversible vis-to-NIR electrochromism with a high optical contrast of 70.6%, suitable for transparent-to-black (TTB) smart window applications.

Visible-Light-Induced, Organophotocatalytic Di- and Trifluoromethylative C-H Annulation Strategy for the Sustainable Synthesis of 5-(Fluoromethyl)-12-quinolino[2,1-]quinazolin-12-ones.

Herein, we disclose a visible-light-induced, oxidative di- and trifluoromethylative annulation strategy with 3-(2-(ethynyl)phenyl)quinazolinones for the sustainable synthesis of new classes of biologically active -heteroaromatics, i.e., 5-(fluoromethyl)-12-quinolino[2,1-]quinazolin-12-ones using 4CzIPN as organophotoredox catalyst and CFHSONa or CFSONa as the -CFH or -CF source, respectively.

5-(Thiophen-2-yl)isoxazoles as novel anti-breast cancer agents targeting ERα: synthesis, biological evaluation, studies, and molecular dynamics simulation.

Herein, we report the design and synthesis of novel 5-(thiophen-2-yl)-4-(trifluoromethyl)isoxazoles (), and evaluation of their anti-cancer activities. Based on the molecular structure of our previously developed isoxazole-based anti-breast cancer lead molecule, 3-(3,4-dimethoxyphenyl)-5-(thiophen-2-yl)-4-(trifluoromethyl)isoxazole (TTI-4), we designed a set of 14 new analogues of TTI-4. The are a synthetically challenging class of molecules, and we synthesized them with high purity by utilizing our in-house developed novel synthetic strategy, , metal-free, cascade regio- and stereoselective trifluoromethyloximation, cyclization, and elimination strategy, with readily available α,β-unsaturated ketones by using commercially available and cheap reagents such as CFSONa and BuONO (cost-effective and sustainable synthesis).

Chromato-Kinetic Fingerprinting Enables Multiomic Digital Counting of Single Disease Biomarker Molecules.

Early and personalized intervention in complex diseases requires robust molecular diagnostics, yet the simultaneous detection of diverse biomarkers─microRNAs (miRNAs), mutant DNAs, and proteins─remains challenging due to low abundance and preprocessing incompatibilities. We present Biomarker Single-molecule Chromato-kinetic multi-Omics Profiling and Enumeration (Bio-SCOPE), a triple-modality, multiplexed detection platform that integrates both chromatic and kinetic fingerprinting for nanoscale molecular profiling through digital encoding. Bio-SCOPE achieves femtomolar sensitivity, single-base mismatch specificity, and minimal matrix interference, enabling precise, parallel quantification of potentially up to nine biomarkers in a single sample with single-molecule resolution.

A unifying model for microRNA-guided silencing of messenger RNAs.

Silencing by the miRNA-guided RNA induced silencing complex (miRISC) is dependent on Ago2-chaperoned base pairing between the miRNA 5' seed (5'S) and a complementary sequence in the 3' untranslated region of an mRNA. Prevailing mechanistic understanding posits that initial 5'S pairing can further allow functional base pair expansion into the 3' non-seed (3'NS), while functionally distinct non-canonical pairing was reported between only the 3'NS and the mRNA coding sequence. We developed single-molecule kinetics through equilibrium Poisson sampling (SiMKEPS) to measure highly precise binding and dissociation rate constants of varying-length target sequences to 5'S and 3'NS in a paradigmatic miRISC isolated from human cells, revealing distinct stable states of miRISC with mutually exclusive 5'S and 3'NS pairing.

A unifying model for microRNA-guided silencing of messenger RNAs.

Silencing by the miRNA-guided RNA induced silencing complex (miRISC) is dependent on Ago2-chaperoned base pairing between the miRNA 5' seed (5'S) and a complementary sequence in the 3' untranslated region of an mRNA. Prevailing mechanistic understanding posits that initial 5'S pairing can further allow functional base pair expansion into the 3' non-seed (3'NS), while functionally distinct non-canonical pairing was reported between only the 3'NS and the mRNA coding sequence. We developed single-molecule kinetics through equilibrium Poisson sampling (SiMKEPS) to measure highly precise binding and dissociation rate constants of varying-length target sequences to 5'S and 3'NS in a paradigmatic miRISC isolated from human cells, revealing distinct stable states of miRISC with mutually exclusive 5'S and 3'NS pairing.

Chromato-kinetic fingerprinting enables multiomic digital counting of single disease biomarker molecules.

Early and personalized intervention in complex diseases requires robust molecular diagnostics, yet the simultaneous detection of diverse biomarkers-microRNAs (miRNAs), mutant DNAs, and proteins-remains challenging due to low abundance and preprocessing incompatibilities. We present Biomarker Single-molecule Chromato-kinetic multi-Omics Profiling and Enumeration (Bio-SCOPE), a next-generation, triple-modality, multiplexed detection platform that integrates both chromatic and kinetic fingerprinting for molecular profiling through digital encoding. Bio-SCOPE achieves femtomolar sensitivity, single-base mismatch specificity, and minimal matrix interference, enabling precise, parallel quantification of up to six biomarkers in a single sample with single-molecule resolution.

Regioselective C-H Thio- and Selenocyanation of Pyrazolo[1,5-a]pyrimidines.

Herein, we report a metal-free, N-chlorosuccinamide (NCS)-mediated, highly efficient, and regioselective C-H thio- and selenocyanation of pyrazolo[1,5-a]pyrimidines using KSCN and KSeCN respectively. The transformation required only NCS (1 equiv) and operated under mild conditions such as ambient temperature and aerobic atmosphere. This method was found to be highly efficient for the C-H thiocyanation of pyrazolo[1,5-a]pyrimidines as compared to our previously developed photocatalytic strategy and also enabled the C-H selenocyanation of the substrates to access 3-selenocyanatopyrazolo[1,5-a]pyrimidines, for the first time, which was unexplored or unsuccessful so far.

HFIP-mediated, regio- and stereoselective hydrosulfenylation of ynamides: a versatile strategy for accessing ketene ,-acetals.

Herein, we report an HFIP-mediated, versatile, sustainable, atom-economical, and regio- and stereoselective hydro-functionalization of ynamides with various -nucleophiles (1 equiv.) such as thiols, thiocarboxylic acids, carbamates, xanthates, and ,-diethyl -hydrogen phosphorothioate to access a wide variety of stereodefined trisubstituted ketene ,-acetals under mild conditions. This protocol requires only HFIP, which plays multiple roles, such as acting as a Brønsted acid to protonate the ynamide regioselectively at the carbon to generate the reactive keteniminium intermediate, stabilizing the intermediate as solvent through H-bonding.

Charge-transfer mediated J-aggregation in red emitting ultra-small-single-benzenic -fluorophore crystals.

Red emission in crystals has been observed with an ultra-small-single-benzenic -fluorophore () with a molecular weight (MW) of only 197 Da, bettering the literature report of fluorophores with the lowest MW = 252 Da. Supramolecular extensive hydrogen-bonding and J-aggregate type centrosymmetric discrete-dimers or a 1D chain of s led to red emission ( = 610-636 nm) in crystals. Unlike in the solution phase showing one absorption band, in thin films and in crystals the transition from the S state to both the S state and S state becomes feasible.

Sustainable and solvent-free synthesis of molecules of pharmaceutical importance by ball milling.

The solvent-free mechanochemical reactions under ball milling have emerged as a promising alternative to traditional solution-based chemistry. This approach not only eliminates the necessity for large quantities of solvents and minimizes waste production, but it also facilitates a unique reaction environment that enables strategies, reactions, and compound syntheses that are typically unattainable in solution. This solvent-less synthetic strategy under ball-milling has been well employed in synthetic organic chemistry in accessing various potential organic molecules including pharmaceutically important molecules and pharmaceuticals or drug-molecules.

Visible-Light-Mediated, Organophotocatalytic C-H Thiocyanation of Pyrazolo[1,5-]pyrimidines.

Herein, we report a metal-free, organophotoredox-catalyzed sustainable C-H thiocyanation of a biologically active class of N-heterocycles, pyrazolo[1,5-]pyrimidines, with potassium thiocyanate (KSCN) using 9-mesityl-10-methylacridinium perchlorate as the photocatalyst (PC) and molecular oxygen as the terminal oxidant under blue-light-emitting diode irradiation at room temperature. The developed catalytic protocol features mild reaction conditions, a broad substrate scope, a high yield of products, and a straightforward scalability. Mechanistic studies revealed a radical pathway involving reductive quenching of the PC by KSCN.

HFIP-Mediated, Highly Chemo-, Regio-, and Stereoselective Hydrofunctionalizations of Ynamides: Access to Stereodefined Alkenes Bearing Drugs and Natural Products.

We disclose a sustainable and versatile synthetic strategy for the highly chemo-, regio-, and stereoselective hydrofunctionalizations of ynamides, through its activation by a solvent, HFIP, to access a wide variety of stereodefined ketene ,, ,, ,, and , acetals in high yield at room temperature. The reaction proceeded through the formation of the reactive keteniminium ion intermediate, formed via protonation at the β-carbon of ynamide by HFIP, followed by an attack of a nucleophile (-addition) at the α-carbon. When ynamides are treated with only HFIP at room temperature, the HFIP addition products of ynamides are formed in a 100% atom-economic fashion; however, in the presence of a stronger -/-/-/-based nucleophile, the corresponding -hydroheterofunctionalized products are formed.

Solvent-Controlled, Atom-Economic, and Highly Regio- and Stereoselective Halo-Chalcogenations of Ynamides: Green Synthesis of Stereodefined Tetrasubstituted Alkenes Bearing Four Different Functional Groups.

The synthesis of stereodefined tetrasubstituted alkenes bearing four different functional groups is challenging. Herein, we disclose a 100% atom-economic and highly regio- and stereoselective halo-chalcogenations, in particular, chlorosulfenylation, bromosulfenylation, chloroselenation, and bromoselenation, of ynamides in toluene at room temperature under an aerobic atmosphere for the synthesis of a wide variety of stereodefined tetrasubstituted alkenes bearing four different functional groups in excellent yields. Notably, all the reactions are highly efficient and furnished the desired products in excellent yield (average yield >96%) and stereoselectivity (/ = 90:10 to >99:1) within a short time (15-30 min).

Electricity-driven, oxidative C-H selenylative and tellurylative annulation of -(2-alkynyl)anilines: sustainable synthesis of 3-selanyl/tellanylquinolines.

A metal- and oxidant-free, radical C-H selenylative and tellurylative annulation of -(2-alkynyl)anilines with diorganyl dichalcogenides is developed under electrochemical conditions for the sustainable synthesis of valuable 3-selanyl/tellanylquinolines up to 92% yield at room temperature. The developed protocol required only electricity as the green reagent and offers high atom economy, broad substrate scope, and efficient scalability.

-Fluorophores: an uncharted ocean of opportunities.

-Fluorophores (MFs) are unique ultra-light (in terms of molecular weight (MW)) fluorophores exhibiting luminescence with a wide colour gamut ranging from blue to the NIR. Single benzenic MFs are easy to synthesize, are quite bright (with photoluminescence quantum yield (PLQY) as high as 63%) and exhibit very large Stokes shift (as high as 260 nm (8965 cm)), with large solvatochromic shift (as high as 175 nm), and very long excited-state-lifetime (as high as 26 ns) for such ultra-light fluorophores. An emission maximum of ≥600 nm has been achieved with an MF in a polar medium having a MW of only 177 g mol and in a nonpolar medium having MW of only 255 g mol; therefore, a large-sized π-conjugated -fluorophore is no longer a prerequisite for red/NIR emission.

Unleashing the power of porphyrin photosensitizers: Illuminating breakthroughs in photodynamic therapy.

This comprehensive review provides the current trends and recent developments of porphyrin-based photosensitizers. We discuss their evolution from first-generation to third-generation compounds, including cutting-edge nanoparticle-integrated derivatives, and explores their pivotal role in advancing photodynamic therapy (PDT) for enhanced cancer treatment. Integrating porphyrins with nanoparticles represents a promising avenue, offering improved selectivity, reduced toxicity, and heightened biocompatibility.

Critical Analysis and Optimization of Stoichiometric Ratio of Drug-Coformer on Cocrystal Design: Molecular Docking, In Vitro and In Vivo Assessment.

In this present research, an attempt has been made to address the influence of drug-coformer stoichiometric ratio on cocrystal design and its impact on improvement of solubility and dissolution, as well as bioavailability of poorly soluble telmisartan. The chemistry behind cocrystallization and the optimization of drug-coformer molar ratio were explored by the molecular docking approach, and theoretical were implemented practically to solve the solubility as well as bioavailability related issues of telmisartan. A new multicomponent solid form, i.

Synthesis of (4-Trifluoromethyl)isoxazoles through a Tandem Trifluoromethyloximation/Cyclization/Elimination Reaction of α,β-Unsaturated Carbonyls.

We disclose a metal-free, cascade regio- and stereoselective trifluormethyloximation, cyclization, and elimination strategy with readily available α,β-unsaturated carbonyl compounds to access a wide variety of pharmaceutically potential heteroaromatics, i.e., 4-(trifluoromethyl)isoxazoles including a trifluoromethyl analogue of an anticancer agent.

Highly sensitive protein detection by aptamer-based single-molecule kinetic fingerprinting.

Sensitive assays of protein biomarkers play critical roles in clinical diagnostics and biomedical research. Such assays typically employ immunoreagents such as monoclonal antibodies that suffer from several drawbacks, including relatively tedious production, significant batch-to-batch variability, and challenges in site-specific, stoichiometric modification with fluorophores or other labels. One proposed alternative to such immunoreagents, nucleic acid aptamers generated by systematic evolution of ligand by exponential enrichment (SELEX), can be chemically synthesized with much greater ease, precision, and reproducibility than antibodies.

Predominance of genomically defined A lineage of HPV16 over D lineage in Indian patients from eastern India with squamous cell carcinoma of the cervix in association with distinct oncogenic phenotypes.

Human papillomavirus type-16 (HPV16) is classified into lineages, A, B, C and D and 10 sub-lineages portraying variable infectivity, persistence, and cytological outcomes, however, with geographical variations. Our objective was to delineate the distinctive features of lineages among cervical squamous cell carcinoma (SCC) in the eastern region of India. A total of 145 SCC cases and 24 non-malignant specimens, harboring episomal HPV16, were included.

Synthesis of Organosulfur and Related Heterocycles under Mechanochemical Conditions.

In the last few decades, ball-milling has received tremendous attention as a "green tool" for conducting various challenging organic transformations under transition-metal-free and solvent-free conditions. Organosulfur and related heterocycles are ubiquitous in numerous biologically active molecules with potential applications, and those molecules could be synthesized from readily available starting materials under mechanochemical conditions without using any hazardous chemical or solvent. This synopsis highlights the green strategies developed in recent times to synthesize organosulfur and related heterocycles under ball-milling conditions.

Iodine-Catalyzed Methylthiolative Annulation of 2-Alkynyl Biaryls with DMSO: A Metal-Free Approach to 9-Sulfenylphenanthrenes.

An iodine-catalyzed sustainable, cost-effective, and atom-economic synthetic methodology is developed to synthesize a wide variety of valuable sulfenylphenanthrenes and polycyclic heteroaromatics in moderate to high yield through electrophilic thiolative annulation of 2-alkynyl biaryls (6- cyclization) using methyl sulfoxides such as dimethyl sulfoxide (DMSO) as the sulfur source under transition-metal-free conditions. The transformation requires only iodine in a catalytic amount and trifluoroacetic anhydride. Notably, DMSO played multiple roles such as methylthiolating reagent, oxidant, and solvent in this reaction.