Ni(II) complexes have been used as electrocatalysts in the hydrogen evolution reaction (HER) to produce clean, environmentally friendly fuel. Geometry around the metal centre may play a crucial role in its electrocatalytic activities. For this purpose, two nickel complexes, [Ni(L1)2] (complex 1) and [Ni(L2)NO3] (complex 2), where HL1 = 1-((2-(pyrrolidin-1-yl)ethylimino)methyl)naphthalen-2-ol and HL2 = 1-((3-((3-aminopropyl)(methyl)amino)propylimino)methyl)naphthalen-2-ol, were synthesized and characterized by different standard methods, including single crystal X-ray diffraction analysis. The Ni in complex 1 is characterized by a square planar geometry, and the metal center in complex 2 is hexacoordinated. Various experiments reveal that (i) the diffusion coefficient of complex 1 (18.01 × 10-2 cm2 s-1) is higher than that of complex 2 (3.45 × 10-2 cm2 s-1), (ii) the overpotential values are 0.47 V and 0.56 V for complex 1 and complex 2, respectively, (iii) the TOF values are 389.5 and 182.5 for complex 1 and complex 2, respectively, and (iv) the faradaic efficiency is 90% for complex 1 and 86% for complex 2. On the basis of the electrochemical results and the DFT-optimized local-minimum structures, an ECEC-type HER pathway is proposed, although other proton-/electron-transfer sequences cannot be ruled out from the present data. These results suggest more robust catalytic activity of complex 1 than complex 2 in the HER.

Transition-metal catalysis in living cells offers a valuable tool in chemical biology for intracellular transformations; however, it is hindered by insufficient catalyst uptake and rapid deactivation in the intracellular environment. This study introduces "Pallado-fingers": Pd(II) complexes derived from a minimal Cys2His2 zinc finger domain, engineered into a His2 scaffold (ZFP2H) to facilitate precise metal coordination and catalysis. Using a fluorogenic propargylated dye, this work demonstrates efficient Pd(II)-mediated de-propargylation in buffer solutions, with activity modulated by the co-ligand/counterion in the order PPh3 > OAc- > Cl-. Notably, this trend is reversed within mammalian cells (A549, HeLa, U2OS), with ZFP2H-PdCl2 emerging as the most effective intracellular catalyst, highlighting the significant influence of the cellular environment on catalyst performance. To address limitations associated with peptide internalization, 4-carboxyphenylboronic acid units were installed to lysine residues, yielding ZFP2HBA that exhibits markedly improved cellular uptake. The complexation of ZFP2HBA with PdCl2 induces a tenfold increase in intracellular de-propargylation, as quantified by flow cytometry and visualized through fluorescence microscopy, followed by an exploration of the internalization pathway using different endocytosis inhibitors. This research establishes boronic acid-assisted delivery of Pallado-fingers as a straightforward, modular strategy to enhance transition metal complex catalysis in living mammalian cells.

Zinc is an essential transition metal ion in our body system. Its deficiency and deposition lead to several health issues. Thus, its detection becomes necessary. For this purpose, we have synthesized a bisphenol A derivative (H2L-Oxy) incorporating a pyridine unit as a chemosensor by a two-step reaction for detection of Zn2+. The probe exhibited a weak emission band at 530 nm in 10 mM HEPES buffer in H2O/DMF = 4: 1 (v/v) (pH 7.4) when it was excited at 410 nm. While in the presence of Zn2+, the fluorescence intensity of H2L-Oxy increased by 12 times at 467 nm with a blue shift of 54 nm. This enhancement of fluorescence intensity has been explained by the restriction of -C--N isomerization, ICT (Intramolecular charge transfer) and CHEF (Chelation enhancement of fluorescence) mechanism. The limit of detection (LOD) of the probe towards the cation was determined as 5.53 x 10- 8 M. H2L-Oxy formed a 1: 2 complex with Zn2+ with an association constant of 1.7 x 104 M- 1. Theoretical calculations have been carried out to support the observed results. It has been applied in imaging of Zn2+ in living cells.

Delivering cargo into live cells has extensive applications in chemistry, biology, and medicine. Cell-penetrating peptides (CPPs) provide an ideal solution for cellular delivery. Enhancing CPPs with additional functional units can improve delivery efficiency. We investigate the conjugation of boronic acid modules to enhance internalization through interactions with cell surface glycans. The aim of this study is to determine whether adding boronic acid can transform a peptide that typically lacks CPP properties into one that functions as a CPP, enabling the delivery of crucial biological cargo like ubiquitin (Ub). The zinc finger protein in its apo state was selected as a "boronate-enabled" CPP. Results indicate that skeletal point mutations and post-synthetic modifications, combined with conjugated benzoboroxole derivatives, enable the apo-ZFP the ability to transport Ub within A549 cells, confirmed through microscopy and flow cytometry. This effective internalization of cargo offers valuable insights for advancing the development of boronic acid-mediated cell-penetrating peptides.

MOFs are extensively utilized for recognizing metal ions. With their tunable structures, opportunities for postsynthetic modification, and chemical stability, MOFs outperform current alternatives by providing unique spectroscopic readings for metal ion detection. We find their recyclability particularly appealing, as it allows repeated use of the same host probe-this aspect is crucial for point-of-care technologies. This review offers an in-depth exploration of metal ion recognition through MOFs, including insights into sensing mechanisms and photophysical properties sourced from more than 130 articles. It serves as a valuable reference for those interested in a comprehensive understanding of knowledge.

We report here discriminative interaction of 3-(((6-chlorobenzo[d]thiazol-2-yl)imino)methyl)-2-hydroxy-5methylbenzaldehyde (HL) with Zn2+, Cu2+ and Ni2+. HL was synthesized by a reaction between 4-methyl-2,6diformyl phenol and 6-chlorobenzo[d]thiazol-2-amine in 1:1 ratio. It showed moderate fluorescence intensity at 530 nm in 10 mM HEPES buffer in water/DMF = 4:1 (v/v) (pH 6.0) upon excitation at 420 nm. On addition of Zn2+, its fluorescence maximum shifted to 480 nm and then its intensity gradually enhanced at 480 nm signifying ratiometric detection of the metal ion. In the presence of Cu2+ and Ni2+, its fluorescence intensity at 530 nm quenched severely. Other metal ions could not alter the fluorescence of HL. Quantum yield of HL changed from 0.166 to 0.299, 0.059 and 0.010 in the presence of Zn2+, Cu2+ and Ni2+, respectively. It formed 1:1 complexes with each of these cations with an association constant of 3.30 x 103, 9.00 x 104 and 9.70 x 104 M- 1 with Zn2+, Cu2+ and Ni2+, respectively. The values of limit of detection were determined to be 3.44 x 10- 8, 3.81 x 10- 8 and 3.30 x 10- 8 M towards Zn2+, Cu2+ and Ni2+, respectively indicating impressive sensitivity. Binding of Zn2+ to HL results in the restriction of C--N isomerization and CHEF mechanism leading to the high fluorescence. Due to the paramagnetic nature of the metal center, fluorescence intensity of HL decreases with Cu2+ and Ni2+. HL was applied in imaging these metal ions in living HeLa cells.

Bispecific agents capable of simultaneously targeting two distinct cell surface receptors promise enhanced specificity and efficacy in cancer therapy. Here, we report a strategy for the rapid optimization of compact bispecific agents using nucleic acid hybridization to display peptide ligands for both the epidermal growth factor receptor (EGFR) and the mesenchymal-epithelial transition factor (MET). The self-assembly process involved 20 and 21 nucleotide (nt) long DNA-peptide conjugates and 41-46 nt template strands, which precisely controlled the spatial arrangement of the EGFR-targeting peptide GE11 and the MET-binding bicyclic peptide GE137. We introduce improved synthetic methods for the challenging construction and functionalization of GE137, enabling its efficient conjugation to oligonucleotides. Systematic variation of peptide spacing revealed a striking distance-dependent affinity profile in interactions with live A549 cells, with optimal staining observed when GE11 and GE137 were separated by 21 paired and 3 unpaired DNA nucleotides. Incorporation of a cleavable cytotoxic payload (monomethyl auristatin E) into bispecific DNA-peptide constructs led to potent, HGF-dependent cytotoxicity, underscoring the requirement for targeted internalization. Conjugation to DNA effectively masked the cytotoxic payload, unless the combined activity of GE11 and GE137 induced internalization. This work establishes that DNA-directed assembly allows precise optimization of bispecific peptide agents that are much smaller than conventional constructs, offering robust targeting and conditional cytotoxicity. These findings highlight the promise of nucleic acid scaffolds for next-generation, cell-selective therapeutics.

Chemical modification and nucleic acid self-assembly can be used to make protein receptor ligands form specific arrangements. While this property has been extensively exploited for probing of homomultivalent interactions, there has been comparatively little attention paid to the exploration of heteromultivalent interactions. In this study, we investigated the use of readily assemblable DNA duplexes for programming bispecific targeting of specific cell types. In contrast to previous bispecific agents, we leverage the potential of peptide-based high-affinity binders of cell surface proteins used in diagnostics/therapeutics. Systematic spatial screening revealed the optimal distance between two (cyclo)peptides required for selectively recognizing cells expressing unique combinations of receptors. The VGFR2/αVβ3 receptor system on HUVECs was tolerant to changes of the distance between two cyclopeptides (L and cyclo(-RGDf(N-Me)K-)) and required that the distance exceeded the equivalent of 20 nucleotides distance. A different distance-affinity landscape was observed for recognition of EGFR and MET on A549 cells (through GE11 and bicyclic peptide GE-137). The DNA-programmed bispecific binders demonstrated specificity and efficient internalization into target cells. Auristatin-loaded DNA enabled a selective targeting of cytotoxic payload. Of note, the distance-optimized bispecific DNA-peptide probes have much lower molecular weight than previously used agents based on DNA nanostructures or antibodies.

This study explores an enhancement to a cell-penetrating peptide (CPP), specifically cyclic deca arginine (cR10), by modifying it with boronic acid to improve the delivery efficiency of ubiquitin (Ub), an essential protein that plays various roles in cellular functions. The hypothesis is that adding boronic acid could boost cellular uptake through glycan-boronic acid interactions. This research assesses how the boronic acid-modified cR10 compares to TAT, a natural CPP derived from the HIV-1 transactivator of transcription, in delivering Ub into cells. Experiments with U2OS cells indicated that the boronic acid-linked cR10Ub cargo achieved a fourfold increase in cellular uptake compared to the TAT-Ub conjugate. The findings from this study could contribute to developing new approaches for enhancing protein delivery methods relevant to biomedical research and therapeutic applications.

Metal mediated several organic reactions are known which can be used inside the cellular medium for protein modifications, eventually for targeting diseases. Indeed, due to their ease of handling, rapid solubility, and effective cell penetration, metals are superior than any other competitor as a stimulus/mediator in organic reactions relevant with protein modifications. Metal mediated most effective reactions as a chemical biology tool are Cu(I)-catalyzed azide-alkyne cycloaddition(CuAAC)/click reactions or Pd mediated multiple chemical reactions for intra/extra cellular protein modifications etc. A few examples of Au(III), Ru(III) are also known. Among these, the click reaction has high potential for the management of biomolecules within cells, and thus this methodology is adopted broadly in chemistry, biology towards therapeutic applications in pharmacology. Fast kinetics in aqueous medium at ambient to normal temperature with specificity between precursors (e. g., azide and alkyne for click reactions which are bio-orthogonal to cells) are essential aspects behind the success of metal mediated intracellular reactions. This review dealt with specifically metal mediated protein modifications within live cells, the achievements and challenges.

Glycosylated RNA (glycoRNA) has recently emerged as a novel constituent of the glycocalyx on cell surfaces, yet its biological functions remain largely unexplored. In this report, we present the first analysis of glycoRNA expression and functionality in alveolar epithelial cells. To this end, we optimized new techniques for the detection of glycoRNA on living cell surfaces and in cell membrane-associated RNA samples through in-gel imaging after labeling with fluorescent dye conjugates. Specifically, we used conjugation of Cy5-hydrazide after mild oxidation with sodium periodate for detection of total cell surface sialoglycoRNA. Conjugation of dibenzocyclooctyne-sulfo-Cy5 in cells fed with tetraacetylated N-azidoacetyl-mannosamine or 6-azido-L-fucose detected de novo-formed sialoglycoRNA or fucoglycoRNA, respectively. Finally, biotinylated lectins in combination with infrared dye-conjugated streptavidin were used to differentiate between specific glycosidic linkages. Comparisons across primary alveolar epithelial cells and different alveolar epithelial-like cell lines revealed a cell-type-specific variation in glycoRNA abundance. Treatment of primary alveolar epithelial cells with an RNase cocktail reduced epithelial surface glycoRNA and was associated with a reduction in transepithelial electrical resistance and influenza A viral particle abundance. As such, the present work identifies glycoRNA as a novel component of the alveolar epithelial glycocalyx with potential relevance in epithelial barrier regulation and viral infection.

Rhodamine probes are highly explored as a host for metal ion recognition. Indeed, along with a single rhodamine unit, bis-rhodamine units are also exploited for the same. Single rhodamine probes are exhaustively studied, whereas bis-rhodamine probes comparatively are younger and less explored, eventually never reviewed separately. Still, bis rhodamine probes have the potential to be individually treated due to multiple reasons such as possibilities of higher sensitivity, better chelation, multi-ion sensing etc. Thus, this review discusses the possibilities of bis-rhodamine probes and possible connections with artificial intelligence and machine learning (AIML) based methods. Several reputed researchers use AI-ML-based methods for multiple uses to fulfil unmet needs. In the case of chemosensors, no such AI-ML-based methods have been reported before. Through this review, the possibility of a promising connection is suggested for chemosensors, particularly bis-rhodamine probes.

Bisphenol A is a fluorophoric platform that is used to develop chemosensors for various species. Here we report one bisphenol A based Schiff-base molecule, 4,4'-(propane-2,2-diyl)bis(2-((E)-((2-hydroxy-5-methylphenyl)imino)methyl)phenol (Me-H4L), as a selective chemosensor...

Cell-penetrating peptides (CPPs) are handy tools for protein/peptide delivery, thus helping in protein therapeutics, understanding versatile protein mechanisms etc. Indeed, CPP attached to the target protein, which is otherwise not cell permeable, can now be delivered to the cell. To explore the role of CPPs in cell delivery, the work will investigate the effect of different CPP scaffolds on cellular uptake. Thus, a poly-arginine (Arg, R) based small CPPs is synthesised. Linear R5 was chosen as the model CPP modified to K2R3 (Lys, K) to explore the influence of Arg within the scaffold. G2R3 (Gly, G) probs the influence of charge as it failed to pass the membrane. To investigate the effect of aromaticity in cellular uptake, F2R3 (Phe, F) was synthesised, which was later modified to Y2R3 (Tyr, Y) to explore the effect of aromaticity along with active -OH groups. S2R3 (Ser, S) was designed to investigate the sole influence of -OH groups in cell delivery. Experiments suggest that R5 outperforms other peptides in cell delivery and was further examined at 37°C and 4°C. Successful cell delivery of R5 at 4°C rules out chances of any energy-dependent cellular uptake pathway, including endocytosis. The probable structural influence of R5 and K2R3 was also investigated using DFT calculation.

Two mononuclear complexes, [Cu(L1)2] (Complex 1) and [Cu(HL2)2](NO3)2 (Complex 2)where HL1 is1-((cyclohexylmethylimino)methyl)-naphthalen-2-ol and HL2 is 4-bromo-2-((2-morpholinoethylimino)methyl)phenol, have been synthesized under mild conditions and characterized by different standard analytical methods. Single...

Studying functional protein delivery into live cells is important, ranging from fundamental research to therapeutics. Cell-penetrating peptides (CPPs) are known to deliver proteins with applauded efficacy and have gained importance for applications in protein therapeutics and exploration of versatile cellular mechanisms. The primary aim of the work is to design a CPP as a tool and delivery vehicle for macromolecules, including proteins. In this work, boronic acid-linked cyclic deca arginine (cR10) is reported as an efficient CPP that exhibited 3-fold higher delivery of chemically synthesized ubiquitin (Ub) than pristine cR10-linked Ub, examined with live U2OS cells. As a futuristic plan, an artificial intelligence machine learning-based rationale has been designed and proposed.