Laxmikanta Khamari

The direct formation of a C-N bond at the ortho-position of naphthalene monoimides (NMI) and perylene monoimides (PMI) is reported herein using dioxazolones as the amide source. This method affords direct access to ortho-amino NMI and PMI through an amidation and deprotection sequence. One-pot telescopic bay-bromination of ortho-amino PMIs was also achieved. The ortho-amidated NMIs and PMIs, accessed by the current methodology, show significant red shifts in their absorption and fluorescence spectra compared with the NMI and PMI alone. An improvement in the quantum yield and fluorescence lifetime was observed by the incorporation of pivalamide groups at the ortho-positions of NMI and PMI.

Intrinsically disordered proteins (IDPs) are a class of proteins that do not follow the unanimated perspective of the structure-function paradigm. IDPs enunciate the dynamics of motions which are often difficult to characterize by a particular experimental or theoretical approach. The chameleon nature of the IDPs is a result of an alteration or transition in their conformation upon binding with ligands. Experimental investigations via ensemble-average approaches to probe this randomness are often difficult to synchronize. Thus, to sense the substates of different conformational ensembles of IDPs, researchers have often targeted approaches based on single-molecule measurements. In this Perspective, we will discuss various single-molecule approaches to explore the conformational transitions of IDPs in different scenarios, the outcome, challenges, and future prospects.

Intercalated-motif (i-motif) DNA formed by cytosine (C)-rich sequences has been considered a novel target in anticancer research. Interestingly, this type of noncanonical DNA structure is highly dynamic and can display several conformational polymorphisms based on the immediate surrounding environment. However, studies regarding the folding pathway of i-motifs having disease-specific sequences under a confined environment at physiological pH are relatively scarce. This thereby warrants more explorations that will decipher their structural and functional properties inside constrained media. Herein, using the single-molecule Förster Resonance Energy Transfer (smFRET) studies, for the first time, we have illustrated the conformational dynamics of c-MYC promoter-based i-motif structures at physiological pH inside microemulsions of different dimensions. We concluded that the folding of such motifs under confined space is not a direct transition between the random coil and i-motif conformations; rather it occurs through a partially folded intermediate, depending on the confined dimension.

This work delineates an integrative approach combining spectroscopic and computational studies to decipher the association-induced fluorescence properties of a fluorescent molecular rotor, viz., auramine O (AuO), after interacting with 20-mer duplex DNA having diverse well-matched base pairs. While exploring the scarcely explored sequence-dependent interaction mechanism of AuO and DNA, we observed that DNA could act as a conducive scaffold to the formation of AuO dimer through noncovalent interactions at lower molecular density. The photophysical properties of AuO depend on the nucleotide compositions as described from sequence-dependent shifting in the emission and absorption maxima. Furthermore, we explored such DNA base pair-dependent fluorescence spectral characteristics of AuO toward discriminating the thermodynamically most stable single nucleotide mismatch in a 20-mer sequence. Our results are interesting and could be useful in developing analogues with further enhanced emission properties toward mismatched DNA sequences.

Understanding the fundamental interactions between plasmonic metal nanoparticles (MNPs) and small molecules is of utmost importance in various applications such as catalysis, sensing, drug delivery, optoelectronics, and surface-enhanced Raman spectroscopy. Herein, we have investigated the early stage of the aggregation pathway of citrate-stabilized Au NPs with surfactants and explored their catalytic efficacy. Our findings reveal that (17 ± 2)-nm-sized citrate-stabilized Au NPs undergo concentration and time-dependent aggregation with positively charged cetyltrimethylammonium bromide (CTAB). Kinetic analyses revealed the presence of two distinct kinds of aggregates, namely, smaller clusters and a larger branched network of Au nanochains. At longer times and in the presence of higher concentrations of CTAB, these branched networks of Au nanochains transform into dense compact globular aggregates. The catalytic efficacy of Au NPs, branched Au nanochains, and dense compact aggregates has been explored with respect to the reductive hydrogenation of 4-nitophenol in the presence of excess NaBH₄. Our study revealed that the catalytic rate decreases in the order of Au NPs > branched Au nanochains > compact aggregates. Interestingly, pre-equilibrating different Au NP samples with excess NaBH₄ prior to the onset of the reaction results in similar catalytic activity irrespective of the aggregation state of Au NPs. This observation has been explained by considering efficient surface restructuring via ligand exchange with H^– ions and the subsequent disruption of CTAB-induced aggregates of Au NPs. Moreover, the aggregated Au NPs can be recycled over several consecutive cycles for the reductive hydrogenation of 4-NP upon ligand exchange with H^– ions. Taken together, our present study highlights the early-stage aggregation kinetics of Au NPs with CTAB surfactants and demonstrates the importance of the surface restructuring of Au NPs on their catalytic efficacy.

Monitoring the DNA dynamics in solution has great potential to develop new nucleic acid-based sensors and devices. With spectroscopic approaches, both at the ensemble average and single-molecule resolution, this study is directed to differentiate a single nucleotide mismatch (SNM) via a metal ion-stabilized mismatched base-pairing (C–Ag⁺–C/C–Cu²⁺–T) (C = cytosine, T = thymine) and site-selective extrinsic fluorophore, specifically, Thioflavin T (ThT). This is the first approach of its kind where dynamic quantities like molecular diffusion coefficients and diffusion times have been utilized to distinguish the least-stable SNM (CC & CT) formed by the most discriminating nucleobase, specifically, cytosine in a 20-mer duplex DNA. Additionally, this work also quantifies metal ions (Ag⁺ and Cu²⁺) at lower concentrations using fluorescence correlation spectroscopy. Our results can provide greater molecular-level insights into the mismatch-dependent metal–DNA interactions and also illuminate ThT as a new fluorophore to monitor the dynamics involved in DNA–metal composites.