Amitava Das

Correction for ‘Reductive microenvironment-activated paclitaxel–BODIPY nanoassemblies for self-reporting drug delivery’ by Deepak Tayde et al. , Org. Biomol. Chem. , 2026, https://doi.org/10.1039/d6ob00954a.

We report the design and synthesis of a redox-responsive paclitaxel–BODIPY conjugate (PTX-SS-BDP) in which paclitaxel is linked to a BODIPY moiety through a glutathione-cleavable disulfide spacer.

The rational design of responsive molecular frameworks that convert molecular recognition into measurable optical signals is crucial for advanced sensing technologies. Herein, we report a preorganized 3D conjugated polymeric receptor integrated with a custom‐built IoT‐enabled photonic platform for the quantitative detection of the advanced explosive TKX‐50. The polymeric receptor ( 2 ), synthesized from tris(4‐aminophenyl)amine (TAPA) and tetraphenylethylene (TPE) motifs, exhibits a selective fluorescence “turn‐on” response toward TKX‐50. Structural and spectroscopic analyses confirm the formation of a thermally robust imine‐linked polymeric framework with spherical morphology. Receptor 2 shows a broad emission band with λ _max ∼600 nm ( Φ _Ems = 0.005, Ru(2,2′‐bipy) ₃ ²⁺ as reference), whereas TKX‐50 binding induces a strong emission at ∼ 475 nm (Φ _Ems = 0.51, Ru(2,2′‐bipy) ₃ ²⁺ as reference), affording an ultralow detection limit of 29.2 nM. Time‐resolved fluorescence and DFT/TD‐DFT studies reveal that hydrogen bonding‐driven charge transfer and excited‐state rigidification suppress nonradiative decay pathways associated with phenyl‐ring rotation. This emission response was utilised for photocurrent generation and the development of a portable IoT‐integrated fluorometric device. A custom‐made LED‐photodiode architecture enables rapid, reproducible, and quantitative detection of TKX‐50. This work integrates purpose‐built polymer design with intelligent optoelectronic engineering, establishing a new paradigm for real‐time, field‐ready detection of energetic materials.

Compartmentalization underpins biological organization and the design of programmable therapeutic carriers. Here, we report a sequence‐defined short peptide, Biotin‐Ser(‐OPO ₃ ^{2 −} )‐Phe‐Phe‐Arg ( Biotin‐SR ), that undergoes physiological liquid–liquid phase separation to form lipid‐free coacervate vesicles (CVs) with enhanced structural persistence. The designer peptide integrates oppositely charged functionalities that drive pH‐responsive coacervation, incorporating an alkaline phosphatase (ALP)‐cleavable anionic phosphoester, a diphenylalanine motif that promotes hydrophobic packing, and a cationic guanidinium group that stabilizes the coacervate architecture while serving as a precursor for nitric oxide (NO) generation. These CVs selectively target cancer cells via biotin‐mediated recognition. CVs of Biotin‐SR  with pronounced morphological persistence, as confirmed by restricted molecular exchange in FRAP analysis, and encapsulate glucose oxidase (GOx) within this stabilized vesicular architecture, undergo ALP‐induced enzymatic dephosphorylation in ALP‐rich tumor environments to trigger an irreversible loss of charge complementarity, GOx release and a synergistic therapeutic cascade integrating enzymatic starvation, oxidative stress amplification, and NO‐mediated mitochondrial dysfunction. The resulting glucose depletion couples with NO generation to elevate reactive oxygen species (ROS), inducing mitochondrial dysfunction and suppressing tumor growth in both spheroids and xenograft models. This work demonstrates how minimal peptide sequences can translate liquid‐liquid phase separation into stable coacervate vesicles with enzyme‐responsive supramolecular function for targeted therapeutics.

Amyloid-β 42 (Aβ-42) misfolding and self-assembly drive proteostatic collapse in Alzheimer’s disease, but chemically programmable systems enabling sequence-selective recognition and remodeling of the Aβ-42 aggregation pathway remain elusive. We report a rationally engineered supramolecular composite, 18C6-LV-PEG, that integrates benzo-18-crown-6 (18C6) to form a supramolecular inclusion complex with the ε-NH₃⁺ group on lysine, a short peptide sequence targeting the ¹⁷LVFF²⁰ motif of Aβ-42, and a PEG appendage to enhance pharmacokinetics and blood–brain barrier permeability. Cooperative multivalent engagement of this motif, confirmed by ¹H–¹⁵N HSQC NMR, confers markedly enhanced affinity (K_a^ITC ∼ 7.4 × 10⁴ M^–1 toward monomeric Aβ-42) relative to individual components (≤10² M^–1), demonstrating synergistic binding. Importantly, 18C6-LV-PEG not only blocks nucleation-dependent Aβ-42 aggregation but also effectively destabilizes soluble oligomers, as well as mature aggregates, revealing a mechanistically distinct supramolecular modulation of the Aβ-42 aggregation pathway relative to conventional inhibitors. The nontoxic conjugate mitigates oxidative stress, restores mitochondrial function, reinstates glial–neuronal connectivity, and improves cognition in an Alzheimer’s model. More broadly, this work introduces a conceptual design principle that integrates precision Lys¹⁶–clamp by 18C6 with targeting of the aggregation-prone ¹⁷LVFF²⁰ motif to enable chemically programmable, multivalent intervention in pathogenic protein assemblies.

Wilson disease (WD) is caused due to mutations in the copper ATPase gene ATP7B, that result in accumulation of labile copper pools and the consequent disruption of cellular redox homeostasis through uncontrolled copper-mediated reactive oxygen species generation. Current therapies mainly depend on high-affinity copper chelation to lower metal burden which sometimes also strip copper from cuproproteins and may disturb physiological copper-dependent processes. It also does not directly suppress pathological copper reactivity i.e., free radical generation, a major driver of WD progression. To overcome these limitations, we have rationally designed Gua-Cu-3, a C₃-symmetric guanidinium-based molecule that can chelate labile copper without metal stripping from cuproproteins due to moderate binding affinity and it has intrinsic antioxidant activity within a single nanosheet-forming supramolecular self-assembly. Spectroscopic, calorimetric, and computational analyses revealed controlled multivalent copper coordination (K _d = 95.4 μM) while radical-scavenging and hydroxyl-radical inhibition assays further revealed potent redox-regulatory activity. In cellular models of copper overload, Gua-Cu-3 treatment reduces ATP7B trafficking from trans-Golgi network, confirming effective intracellular copper sequestration. This was accompanied by a marked reduction in oxidative stress, reduction of translocation of Nrf2 in nucleus and of HO-1 expression, thereby limiting lipid peroxidation which leads to restoration of cellular homeostasis, including improved lysosomal integrity, reduced endoplasmic reticulum stress, decreased mitochondrial superoxide levels, and diminished apoptosis. Importantly, the protective effects extended, beyond cultured cells, Gua-Cu-3 attenuates oxidative stress in ATP7B-homolog-deficient C. elegans and rescues copper-induced developmental defects in zebrafish, outperforming D-penicillamine, which is currently in use for Wilson disease management. These findings establish Gua-Cu-3 as a molecularly designed supramolecular copper-reactivity buffer that couples-controlled copper sequestration with redox regulation which is distinct from conventional copper depletion and provides a framework for treating Wilson disease and other disorders associated with metal dyshomeostasis and oxidative stress.

Methicillin‐resistant Staphylococcus aureus (MRSA) remains a significant global health threat, necessitating the development of new antimicrobials. We report the rational design of a small molecule TPL(II)‐07, that combines multiple functional modules: (i) 2‐phenylthiophene for specific recognition and binding to lipid II, a key intermediate in peptidoglycan biosynthesis; (ii) an adamantane fragment with high interfacial permeability to destabilize lipid packing; (iii) a cationic lysine moiety to disperse biofilms; and (iv) a moderate aliphatic chain to disrupt membrane integrity. Among seven analogues, TPL(II)‐07 exhibited the highest potency, highlighting the synergistic contribution of each component. Mechanistic assays confirmed preferential binding of lipid II, bactericidal potency, biofilm dispersion, and the generation of reactive oxygen species, effective against both drug‐resistant (MIC 19 µM) and drug‐sensitive (MIC 9 µM) S. aureus strains. TPL(II)‐07 demonstrated excellent biocompatibility, with IC ₅₀ > 50 mM in HEK‐293 and WI38 cells and negligible hemolytic activity. In addition, it suppressed key virulence traits, including hemolysin activity, biofilm formation, and staphyloxanthin production. Further, a borate‐functionalized guar gum hydrogel incorporating TPL(II)‐07 achieved effective infection control and enhanced wound repair in a murine excisional model, establishing thiophene‐based lipid II targeting as a versatile platform for next‐generation antimicrobials with dual antibacterial and wound‐healing potential.

Methicillin‐resistant Staphylococcus aureus (MRSA) remains a significant global health threat, necessitating the development of new antimicrobials. We report the rational design of a small molecule TPL(II)‐07, that combines multiple functional modules: (i) 2‐phenylthiophene for specific recognition and binding to lipid II, a key intermediate in peptidoglycan biosynthesis; (ii) an adamantane fragment with high interfacial permeability to destabilize lipid packing; (iii) a cationic lysine moiety to disperse biofilms; and (iv) a moderate aliphatic chain to disrupt membrane integrity. Among seven analogues, TPL(II)‐07 exhibited the highest potency, highlighting the synergistic contribution of each component. Mechanistic assays confirmed preferential binding of lipid II, bactericidal potency, biofilm dispersion, and the generation of reactive oxygen species, effective against both drug‐resistant (MIC 19 µM) and drug‐sensitive (MIC 9 µM) S. aureus strains. TPL(II)‐07 demonstrated excellent biocompatibility, with IC ₅₀ > 50 mM in HEK‐293 and WI38 cells and negligible hemolytic activity. In addition, it suppressed key virulence traits, including hemolysin activity, biofilm formation, and staphyloxanthin production. Further, a borate‐functionalized guar gum hydrogel incorporating TPL(II)‐07 achieved effective infection control and enhanced wound repair in a murine excisional model, establishing thiophene‐based lipid II targeting as a versatile platform for next‐generation antimicrobials with dual antibacterial and wound‐healing potential.

Mimicking the efficiency of natural photosynthesis for multielectron CO ₂ photoreduction remains a central challenge in solar fuel research. Toward this goal, we developed herein a noble metal free supramolecular ion‐pair assembly comprising rhodamine B ( RB ), an underexplored organic photosensitizer, and a cobalt(II) tris(2‐pyridylmethyl)amine complex ( 1Co ), which self‐assembles into core–shell nano/micro‐assembly via counterion‐mediated contact ion pairing. This confined ion pair architecture promotes counterion mediated, light‐driven hopping electron transfer, suppressing geminate recombination and enabling efficient charge migration, as demonstrated by optical spectroscopy, femtosecond–nanosecond transient absorption, electrochemical impedance spectroscopy, and 2D mass spectrometry studies. Orthogonal dual‐light excitation activates radical anion excited states (RB ^•−* ) within the assembly, enabling a diffusion‐independent cascade electron transfer pathway. This unique approach achieves selective CO ₂ photoreduction to syngas under single‐light irradiation and switches product distribution toward methane generation under dual‐light conditions‐ a rare feat for photocatalytic CO ₂ reduction systems. This work introduces a generalizable supramolecular ion‐pairing strategy for engineering spatially preorganized donor–acceptor architectures that harness high‐energy radical excited states for sustainable solar fuel generation.