Angle-resolved plasmonic photocapacitance of gold nanorod dimers.

The assembly of nanostructures with plausible statistical orientations has provided the opportunity to correlate physical observables to develop a diverse range of niche applications. The dimeric configurations of gold nanorods have been chosen as atypical model systems to correlate optoelectronic with mechanical properties at a number of combinations of angular orientations. Metals are considered as conductors in electronics and reflectors in optics - therefore, metallic particles at the nanoscale exhibit unique optoelectronic characteristics that enable the design of materials to meet the demand of the modern world. Gold nanorods have often been adopted as prototypical anisotropic nanostructures owing to their excellent shape-selective plasmonic tunability in the vis-NIR region. When a pair of metallic nanostructures is sufficiently close to exhibit electromagnetic interaction, the evolution of collective plasmon modes, substantial enhancement of the near-field and strong squeezing of the electromagnetic energy at the interparticle spatial region of the dimeric nanostructures occur. The localised surface plasmon resonance energies of the nanostructured dimers strongly depend on the geometry as well as the relative configurations of the neighbouring particle pairs. Recent advances in the 'tips and tricks' guide have even made it possible to assemble anisotropic nanostructures in a colloidal dispersion. The optoelectronic characteristics of gold nanorod homodimers at different mutual orientations with statistical variation of the angle between 0 and 90° at particular interparticle distances have been elucidated from both theoretical and experimental perspectives. It has been observed that the optoelectronic properties are governed by mechanical aspects of the nanorods at different angular orientations of the dimers. Therefore, we have approached the design of an optoelectronic landscape through the correlation of the plasmonics and photocapacitance through the optical torque of gold nanorod dimers.

Switching of the Polarity-Sensitive Aggregation Pattern of a Thiosemicarbazone-Based Anticancer Luminophore and Its Involvement in Cellular Apoptosis of the Human Lung Cancer Cell Line.

Elucidation of the photophysical and biochemical properties of small molecules can facilitate their applications as prospective therapeutic imaging (theragnostic) agents. Herein, we demonstrate the luminescence behavior of a strategically designed potential therapeutic thiosemicarbazone derivative, (E)-1-(4-(diethylamino)-2-hydroxybenzylidene)-4,4-dimethylthiosemicarbazide (DAHTS), accompanied by the illustration of its solvation and solvation dynamics using spectroscopic techniques and exploring its promising antitumor activities by adopting the necessary biochemical assays. Solvent-dependent photophysical properties, namely UV-vis absorption, fluorescence emission, and excitation profiles, concentration-dependent studies, and time-resolved fluorescence decays, serve as footprints to explain the existence of DAHTS monomers, its excited-state intramolecular proton transfer (ESIPT) product, and dimeric and aggregated forms. The emission intensity progressively intensifies with increasing polarity and proticity of the solvents up to MeOH, but in water, a sudden dip is seen. Solvent polarity and H-bonding modulate the fluorescence behavior of the primary emission peak and significantly influence the formation of the dimer and DAHTS aggregates. The designed luminophore (DAHTS) exhibits significant antiproliferative activity against the human lung cancer (A549) cell lines with inhibitory concentrations (IC50) of 16.88 and 11.92 µM for 24 and 48 h, respectively. DAHTS effectively reduces the cell viability and induces cytotoxicity with extensive morphological changes in A549 cells in the form of spikes when compared to the normal HEK cell lines. More importantly, it increases the p53 expression at the mRNA level that consolidates its potential therapeutic activity. The effect of DAHTS on apoptotic pathways against the A549 cell line has been investigated to determine its probable mechanism of cell death. Thus, the all-inclusive understanding of the photophysical properties and the necessary biochemical assays put forward important steps toward tailoring the thiosemicarbazone core structure for favorable cancer theragnostic applications in academic and pharmaceutical research.

Effect of artificial sweetener saccharin on lysozyme aggregation: A combined spectroscopic and in silico approach.

The use of saccharin in food products attracts much attention as it involves the risk of lethal allergies and many protein aggregation diseases. However, its role in protein aggregation has not been explored to date. This study embodies the effect of artificial sweeteners on HEWL in the absence and presence of commonly available natural products such as curcumin and EGCG. Various techniques have been used to characterize the protein interaction, such as steady-state emission and time-resolved fluorescence, FTIR, gel electrophoresis, TEM, and molecular docking. Steady-state and time-resolved studies revealed the binding strength and concomitant effect of saccharin on HEWL protein. Kinetic measurements revealed that saccharin causes significant enhancement of HEWL aggregation with a considerable reduction in lag phase time i.e. from 37 hr to 08 hr. Whereas in the presence of natural products, the effect of saccharin on HEWL aggregation was significantly reduced specifically in the case of curcumin. The result obtained in the fluorescence experiment were also supported by the gel electrophoresis technique and morphological images taken by TEM. The rapid change in the secondary structure of the protein in the presence of saccharin was confirmed by the FTIR spectroscopy technique. This study is instrumental in understanding the effect of saccharin on protein aggregation and the role of commonly available natural products in curbing its effect.

A Catalogue of Indian Hydraenidae (Insecta: Coleoptera).

This catalogue lists 46 valid species included in 7 genera and two subfamilies of the family Hydraenidae (Coleoptera), recorded from India. The subfamily Hydraeninae accommodates 24 species (5 genera), and Ochthebiinae 22 species (2 genera). We include synonyms, type localities, type depositories, and distribution of the species. The Himalayan region supports the maximum diversity (31 species), followed by Deccan Peninsula (5 species), Western-Ghats (5 species), Northeast (4 species), Gangetic Plains (4 species), Semi-Arid (2 species), and Islands (one species).

Photothermal Reshaping of One-Dimensional Plasmonic Polymers: From Colloidal Dispersion to Living Cells.

Cellular internalization of plasmonic metal nanostructured materials has recently become a requisite for biomedical engineering of several intracellular processes that could foster an extensive paradigm to perform desired functions in the living cells. While numerous anisotropic metal nanostructures can be employed to pursue the specific functions, their incorporation becomes restricted due to morphological specificity to be engulfed in the cells. Due to recent advent in the self-assembly strategies, individual gold nanospheres could be interdigitated to one-dimensional plasmonic polymers and undergo subsequent laser-induced photothermal reshaping to rod-like nanostructures. The salient feature of biological significance is merely the variation of particle size within the polymers that engenders a dramatic impact on the radiative and nonradiative properties expressed in the scale of Faraday number (F a) and Joule number (J 0), respectively, as a function of the aspect ratio (α) of the nanorods. The effect on the nonradiative properties augments designing of nanoscale thermometry essential for photothermal applications in living cells. The conception of the colloidal dispersion has been extended to the cellular environment in a mice model; the selective accumulation of the nanostructures in the cells could provide an invading relationship between plasmonic characteristics, temperature distribution, and the biological issues. The critical correlation between optical and thermal characteristics toward biomedical manipulation from both theoretical and experimental perspectives could augment a milestone toward the progress of modern medical sciences.

Vibration-Assisted Intersystem Crossing in the Ultrafast Excited-State Relaxation Dynamics of Halocoumarins.

Due to its numerous applications, triplet formation and resulting phosphorescence remain a frontier area of research for over eight decades. Facile intersystem crossing (ISC) is the primary requirement for triplet formation and observation of phosphorescence. The incorporation of a heavy atom in molecules is one of the common approaches employed to facilitate ISC. A detailed study of the excited state dynamics that governs ISC is necessary to understand the mechanism of heavy atom effect (HAE). Incorporation of iodine at the 3 position of coumarin-1 reduces fluorescence quantum yield (ϕf) drastically as expected, whereas bromine substitution at the same position increased the ϕf. Such a contrasting effect of the two heavy atoms suggests that there are other features yet to be discovered to fully understand the HAE. Detailed steady state and femtosecond transient absorption studies along with theoretical calculations suggest that the C3-X (X = Br, I) bond vibration plays an important role in the ISC process. The study reveals that while in the case of the iodo-derivative there is no energy barrier in the singlet triplet crossing path, there is a barrier in the case of the bromo-derivative, which slows the ISC process. Such an unexpected phenomenon is not limited to halocoumarins as this rationalizes the photobehavior of 1-bromo-/iodo-substituted naphthalenes as well.

Unusual higher-order nonlinear optical properties in Au-coated triangular Ag-Au nanostructures.

Here, we report hitherto unobserved local field (LF)-assisted pump wavelength-dependent nonlinear optical (NLO) effects of three-photon (3PA)-induced four-photon absorption (4PA) at 532 nm and two-photon-induced 3PA at 730 nm in triangular-shaped core-shell Ag-Au nanoparticles (TrAg@Au) by femtosecond Z-scan. The shell thickness-dependent enhancement in the LF is observed by a COMSOL simulation. The intensity-dependent interplay between saturable and reverse-saturable absorptions along with switching of nonlinear (NL) phase is reported at 730 nm, showing the superiority of TrAg@Au in optical switching (OS). The optical limiting (OL) threshold (Fth) of 5.9(6.5)mJ/cm2 at 730 (532) nm boost their potential over benchmarked materials.

Plasmonic Sensing: Connecting the Dots.

Plasmonic sensitivity of noble metals has often been attributed to the morphology of the nanostructures and dielectric effects of both the materials and the surrounding medium. The measurable plasmonic shift with respect to the change in local dielectric as a function of analyte concentrations within nanoscale volume forms the basis of plasmonic sensing. However, the situation of the surrounding medium in the presence of multicomponent systems and, moreover, inhomogeneous adsorption around the anisotropic nanostructures become seemingly complicated as the precise description of several individual components becomes nearly impossible. Therefore, we have designed a retrospective formalism through a critical condensation of the electromagnetic scattering theories, macroscopic mixing rules, and micromechanics at the metal-analyte interface that can be adopted as generalized model irrespective of morphology of the nanostructures and the nature of analytes to account for the response of all the individual (microscopic) components to the observed (macroscopic) plasmonic sensing.

Stabilization of a potential anticancer thiosemicarbazone derivative in Sudlow site I of human serum albumin: In vitro spectroscopy coupled with molecular dynamics simulation.

Human Serum Albumin (HSA) is the most important protein in human blood plasma and can acts as a major transporting agent for various drug molecules with flexible binding interaction. To elucidate the interaction of a newly designed potential anticancer thiosemicarbazone based luminophore (E)-1-(4-(diethylamino)-2-hydroxybenzylidene)-4,4-dimethyl-thiosemicarbazide (DAHTS) with HSA under physiological condition, in vitro optical spectroscopic experiments viz UV-Vis absorption, steady state fluorescence, fluroscence anisotropy, time resolved fluorscence (TRF) and cicular dichroism (CD) spectroscopy have been scrutinised. The experimental findings have been corroborated with in silico molecular docking analysis and Molecular Dynamics (MD) simulation. The spectroscopic results demonstrated that the conventionally anion-favouring Sudlow site I of HSA copiously adapt neutral DAHTS molecule with moderate binding affinity. The mean fluorescence lifetime of the sole tryptophan (Trp-214) present in the macromolecule experiences an appreciable diminution with an increase in concentration of the synthesized molecule. DAHTS localize itself close to Trp-214 within subdomain IIA (Sudlow site I) and surrounded by multiple hydrophobic amino acid residues (Val-235, Val-231, Ala-229, Phe-228, Val-325, Phe-326, Leu-327, Met-329, Phe-330, Leu-331, Tyr-332, Leu-346, Leu-347, Val-482, Leu-349, Ala-350, Ala-210, Trp-214, Ala- 213 and Val-216) in HSA. The distinct fluorescence lifetime, diverse pathways and changing rate of population indicates that the rotamerisation of Trp-214 residue is controlled by the guest molecule. Sudlow site I of HSA behaves flexibly and induces an allosteric modulation in the macromolecule resulting a minor deformation in the protein secondary structure as observed in CD (observed 11% change of α-helix content) as well as in MD simulation. The integrated multi-spectroscopic research described herein provides several important information about the binding interaction of a thiosemicarbazone Schiff base with HSA, which can be very significant for thiosemicarbazone based drug designing for academia as well as industry.

Diversity in the Family of Manganese Oxides at the Nanoscale: From Fundamentals to Applications.

The interesting chemistry of manganese is due to its various oxidation states. The possibility of several oxidation states has offered the element a special position among the transition metal elements in the periodic table. Amidst the possible oxidation states of manganese (in the range of -3 to +7), the +2, +3, and +4 oxidation states are the most prevalent in nature. Manganese possesses the ability to form multiple bonds with oxygen through spontaneous oxidation to a variety of stoichiometric oxides/hydroxides/oxyhydroxides that are collectively coined as "manganese oxides". However, using the recent advances in the synthetic strategies and characterization techniques over the past couple of decades, the investigation of the physicochemical properties of manganese oxides has been extended up to the nanoscale dimensions beyond the molecular. Moreover, the family of the manganese oxides also includes a series of porous architectures that are, often, stabilized at the nanoscale dimensions. Exquisite synthetic control over the size, shape, organization, and mass production of a variety of oxides at the nanoscale dimensions renders outstanding structural, optical, catalytic, magnetic, and transport properties. The tunable properties along with the chemical and biological accessibility open up new opportunities in a diverse range of niche applications critical to global society. Therefore, beyond the multivariance, polymorphism, thermodynamics, phase transition, crystallinity, magnetism, semiconducting behavior, and biogenecity may serve as the key factors to describe the compelling applications in health and other fields and to further understand the manganese oxides at the nanoscale.

Synthesis and Characterization of Acid-Responsive Luminescent Fe(II) Metallopolymers of Rigid and Flexible Backbone N-Donor Multidentate Conjugated Ligands.

In this report we have disclosed the syntheses and properties of two new conjugated organic moieties bearing the same coordination sites but possessing different backbone rigidities and rotational flexibilities. Two new metallopolymers have been synthesized from the corresponding ligands under identical reaction conditions, and they have been thoroughly characterized through different techniques to understand the effect of backbone rigidity on the evolution of different properties in these metallopolymers. A FESEM micrograph of the rigid metallopolymer confirms the formation of a rigid nanorod type structure, while long agglomerated nanofiber strands are visible on the substrate in the case of the flexible analogue. All of the newly synthesized materials are fluorescence active. An Fe(II) metallopolymer of the flexible ligand showed huge changes in emission properties in the presence of different acids and showed a possibility of it being used as a thin film acid vapor sensor. All of the materials showed reversible electrochemical activity, and both of these polymers have shown electroluminescence when an appropriate potential is applied.

The consequences of adopting therapeutic luminophore azapodophyllotoxin into BSA: a molecular regulator to control emissive population of two tryptophan residues in carrier protein.

Bovine serum albumin (BSA) is a widely recognized plasma protein for its ubiquitous function as one of the paramount transporter of different drugs and enzymes inside biological systems. HPFQ, a member of azapodophyllotoxin family, has been observed to be highly bioactive against a majority of cancer cell lines; while subsequently showing impressive fluorescent properties throughout the polarity scale. However, further pursuit into compliance of this bioactive fluorophore with carrier protein remains imperative for excavating its suitable transporter inside human body. The present biophysical spectroscopic study attempts to exhibit the adaptability of BSA towards a potential therapeutic fluorophore (HPFQ) by combining in vitro optical spectroscopy and in silico molecular docking. The competitive site-binding studies demonstrated that BSA nurtures neutral anti-cancer fluorophore HPFQ into Sudlow site I, where it experiences varying interactions with surrounding hydrophobic amino acid residues viz. Phe 205, Trp 213, Ala 209, Leu 330, Ala 349, Leu 480 etc. HPFQ gets accommodated at the vicinity of Trp-213 in BSA and initiates operation of FRET between them. Adaptation of HPFQ encourages an allosteric modulation, leading to a minor deformation in secondary protein structure, which probably allows the invading water molecules to increase the micropolarity of the adjacent environment around Trp-213. HPFQ assumes to administer conformational alteration in BSA and regulate emissive population of two tryptophan residues Trp-134 and Trp-213. The amalgamated spectroscopic investigation described herein may encourage design of azapodophyllotoxin based potential therapeutic agents for effective in vivo bio-circulation using BSA-based drug distribution systems.Communicated by Ramaswamy H. Sarma.

Entrapment in micellar assemblies switches the excimer population of potential therapeutic luminophore azapodophyllotoxin.

Azapodophyllotoxin is a new class of anti-tumor agent with brilliant therapeutic activity and understanding its physicochemical nature in bio-mimetic microenvironments may provide substantial importance in context of its intercellular localization, efficacy as well as delivery. The present work epitomizes environment-sensitive fluorescence modulation of a prodigy, 4-(2-Hydroxyethyl)-10-phenyl-3,4,6,7,8,10- hexahydro-1H-cyclopenta[g]furo[3,4-b]quinoline-1-one (HPFQ) from the class of anti-cancer agent Azapodophyllotoxin, in differently charged model bio-mimetic micellar microenvironment of cationic CTAB, anionic SDS and neutral Triton X-100 using UV-visible absorption, steady state fluorescence, time-resolved fluorescence and fluorescence anisotropy studies. As a distinct phenomenon, anticancer HPFQ exhibits prolific fluorescence in solvents of varying polarity, originating from a mixed contribution of locally excited, charge transfer and excimer emission. A dramatic modulation in the photophysics of HPFQ has been observed in two types of surfactant consortiums: pre-micellar and post-micellar at physiological and anoxic pH. On photo-excitation, anti-cancer HPFQ exists in monomer-excimer equilibrium with varying ratios in different polarity regions. The marked enhancement in fluorescence intensity of HPFQ in post-micellar region of the surfactant under study probably arises due to regeneration of the monomer from its excimer. This reoccurrence reduces the possibility of Förster resonance energy transfer (FRET) from monomer to excimer, which essentially increases the desired emission intensity. Localization of HPFQ in micellar systems highly depends on polarity gradient inside the micelle, electrostatic, hydrophobic and intermolecular hydrogen bonding interactions. Further corroboration with the polarity sensitive experiments in dioxane-water mixture indicates towards spatial localization of the probe molecule in the stern layer of cationic CTAB, sheer surface of neutral TX100 and outer Gouy-Chapman layer in anionic SDS micelles. A molecular binary logic gate correlates the dominance of micellization over the polarity factor, which enhances the fluorescence response of HPFQ. The enhancement of the emissive potential of anti-cancer HPFQ in biomimetic environments by switching its excimer population may have an immense importance to achieve the status of a dual therapeutic and imaging agent altogether in progressive biomedical research.

Biomimetic systems trigger a benzothiazole based molecular switch to 'turn on' fluorescence.

Molecular switches are valuable tools for the detection of many chemical and biological processes. On the other hand, Schiff bases are known for their simplicity in synthesis and their enormous biochemical applications. In this scenario, when a strategically designed Schiff base acts as a molecular switch in biomimetic environments drags inevitable attention. In this article, we hereby demonstrate an interesting behavior of a strategically designed bioactive benzothiazole based Schiff base (E)-2-(((6-chlorobenzo[d]thiazol-2-ylimino)methyl)-5-diethylamino) phenol (CBMDP) whose fluorescence characteristics dramatically modulate as consequence of its structural modification in aqueous and biomimetic environments individually. Electronic absorption, steady state and time resolved fluorescence spectroscopic techniques along with DFT based quantum chemical calculation evidence that in pure organic solvents CBMDP exists in highly fluorescent enol-imine (N) form which transform into feebly fluorescent hydrated species (H) in bulk aqueous media. Contrariwise, on interaction with the ionic and non-ionic micellar media or with liposome, a structural restoration occurs from less fluorescent hydrated (H) species into a highly fluorescent normal (N) one. This molecular flipping of the title compound upon micellar compartmentalization is possibly caused by the micropolarity of the local environment and further supported by its spectral behavior in different polarity gradient solvent mixture of water-dioxane (protic-aprotic) and water-methanol (protic -protic). Usually, Schiff bases are prone to hydrolysis in aqueous media, interestingly, the structural framework of this strategically designed molecule only allow the first step of hydrolysis, which is hydration of azomethine linkage whereas it withstand the second step, and that possibly helps the structural restoration process. Hence the article described herein may emphasize how a systematically designed Schiff base framework can be used as 'turn off- turn on' fluorescent molecular switch which may be extremely useful for its applications in the area of biochemical sensors.

Manipulating the confinement of electromagnetic field in size-specific gold nanoparticles dimers and trimers.

The intriguing light-matter interactions can be governed by controlling the particle size and shape, electromagnetic interactions and dielectric properties and local environment of the metal nanostructures. Amongst the different approaches that have been engendered to manipulate light at the nanoscale, the self-assembly of metallic nanostructures with controllable interparticle distances and angular orientations, which strongly impact their optical attributes, is one of the viable avenues to exploit their utility in a diverse range of niche applications. The simplest geometrical architectures that enable such modulations are dimers with changeable interparticle distances and trimers with an additional degree of angular orientation to correlate the plasmonic observables with the observed spectral characteristics. Wet chemical approaches have been adopted in this study for the synthesis of size-selective gold nanoparticles, and appropriate organic linkers have judiciously been employed to induce plasmonic interactions amongst the gold nanoparticles in close proximity to each other. The combination of experimental observations and electromagnetic simulations adopted to probe the plasmonic interactions revealed that the electrodynamic coupling effect was very sensitive to particle size, interparticle distances and angular orientations in these simple nanoassemblies. The capability to precisely manipulate the electric field at the junctions between these plasmon-coupled nanoparticles could pave the way for the application of these nanoassemblies in surface-enhanced spectroscopies and sensing applications.

A novel quinoline-appended chalcone derivative as potential Plasmodium falciparum gametocytocide.

BACKGROUND & OBJECTIVES: Malaria has remained a global health problem despite the effective control and treatment measures. In the backdrop of drug resistance, developing novel hybrid molecules targeting the sexual stages (gametocytes) of the human malaria parasite Plasmodium falciparum is of great significance. Recently, chalcone- based polyphenols have generated a great interest in the malaria research community worldwide due to their ease of synthesis and significant biological activity. The primary objective of this study was to investigate the interaction of a newly synthesized quinoline-appended chalcone derivative (ADMQ) with gametocyte specific proteins, Pfg 27 and Pfs 25 and explore its in vitro gametocytocidal potential. METHODS: The characterization of ligand-protein interactions at the atomistic level was done by a simulation strategy that combines molecular docking and molecular dynamics (MD) simulation in a coherent workflow. The X-ray crystal structure of Pfg 27 was retrieved from protein data bank and Pfs 25 was built using the Iterative Threading ASSembly Refinement (I-TASSER) server. The detailed interaction of both ADMQ and a known gametocytocidal agent, methylene blue (MB) (used as a positive control) with gametocyte proteins Pfg 27 and Pfs 25 was studied with a 50 ns explicit MD simulation. The ligand binding pose in terms of glide score, molecular mechanics-generalized born surface area (MM-GBSA) binding energies, protein-ligand root-mean-square-deviation (RMSD) and secondary structure elements (SSE) changes were analyzed accordingly. The direct effect of ADMQ on structural integrity of P. falciparum gametocytes was also examined using in vitro microscopy. RESULTS: The analogous Glide score and MM-GBSA free energy of binding indicated stable interactions for both ADMQ and MB harboured in the active site of targeted gametocyte proteins, Pfg 27 and Pfs 25, separately. Explicit MD simulation by Desmond software package indicated similar distinguishable conformational changes in the active site of target polypeptide chain due to the specific accommodation of ADMQ molecule. The simulation also manifested comparable mechanistic profile in terms of protein-ligand RMSD and changes in secondary structure elements (SSE). Further, ADMQ treatment was found to adversely affect the structural integrity of gametocytes, which resulted in appearance of vesicles protruding from the gametocytes. INTERPRETATION & CONCLUSION: The consolidated in silico molecular modeling and in vitro study described herein may give an insight into the interaction patterns of quinoline-chalcone hybrids with critical gametocyte proteins in the mosquito. This study will possibly pave the way for further exploration of similar heterocyclic quinoline-chalcone hybrids to open up new avenues in drug candidate development against P. falciparum gametocytes.

Switching of Trp-214 intrinsic rotamer population in human serum albumin: An insight into the aftermath of embracing therapeutic bioorganic luminophore azapodophyllotoxin into sudlow site I.

Human serum albumin is perceived to be the most abundant protein in human blood plasma and functions as a major carrier of different enzymes and drugs inside human body. The present article puts in an effort to demonstrate the attitude adopted by human serum albumin towards a potential therapeutic luminophore 4-(2-Hydroxyethyl)-10-phenyl-3,4,6,7,8,10-hexahydro-1H-cyclopenta[g]furo[3,4-b]quinoline-1-one (HPFQ). HPFQ is a prodigy from azapodophyllotoxin class of compounds, which have been synthesized from the perspective of improved bioactivity than its prologue podophyllotoxins. While, HPFQ has proved to be highly bioactive against most cancer cell lines with best GI50 values of <0.1 µM for a major number of cell lines; it also showed terrific fluorescent properties throughout the polarity scale, worthy of a promising imaging agent. The binding mechanism of HPFQ with HSA has been established by combining in vitro spectroscopic techniques, in silico molecular docking and induced fit docking (IFD). The competitive site-binding studies demonstrated that the otherwise anion-receptor sudlow site I of HSA nurtures neutral HPFQ with prudent affinity (Binding constant, Kb = 0.74 × 105 M-1). The time-resolve fluorescence studies reveal an appreciable reduction in HSA average radiative lifetime against an increase in HPFQ concentration and provided evidence for Forster's resonance energy transfer (FRET) being responsible for the dominant quenching mechanism, escorted by minor structural deformations in the backbone of protein structure. HPFQ institutes itself near Trp-214 within protein matrix, and subsequently the "hydrophobic amino acids" dominated cybotactic environment of Trp-214 experiences a reduction in the micropolarity. The allosteric modulation triggered by the stronger association of HPFQ with HSA leads towards minor deformation in secondary structure of protein. Sudlow site I of HSA proficiently embraces a favourable conformation like malleable dough to furnish space for arriving bioactive HPFQ molecule. HPFQ is also believed to administer the conformational regulation in HSA domain by affecting inter-conversion of HSA rotamers, which may prove to be an enlightening area to decode the preferable interaction between them. The juxtaposed spectroscopic research described herein is expected to embolden design of azapodophyllotoxin based anti-proliferative clinical agents for efficient in vivo bio-distribution employing HSA-centred drug delivery and administration systems.

Unveiling the Potential of Unfused Bichromophoric Naphthalimide To Induce Cytotoxicity by Binding to Tubulin: Breaks Monotony of Naphthalimides as Conventional Intercalators.

In the development of small-molecule drug candidates, naphthalimide-based compounds hold a very important position as potent anticancer agents with considerable safety in drug discoveries. Being synthetically and readily accessible, naphthalimide compounds with planar architecture have been developed mostly as DNA-targeting intercalators. However, in this article, it is demonstrated, for the first time, that an unfused naphthalimide-benzothiazole bichromophoric compound 2-(6-chlorobenzo[ d] thiazol-2-yl)-1 H-benzo[ de] isoquinoline-1,3(2 H)-dione (CBIQD), seems to expand the bioactivity of naphthalimide as anti-mitotic agent also. Preliminary studies demonstrate that CBIQD interferes with human lung cancer (A549) cell proliferation and growth and causes cellular morphological changes. However, the underlying mechanism of its antitumor action and primary cellular target in A549 cells remained skeptical. Confocal microscopy in A549 cells revealed disruption of interphase microtubule (MT) network and formation of aberrant multipolar spindle. Consistent with microscopy results, UV-vis, steady-state fluorescence, and time-resolved fluorescence (TRF) studies demonstrate that CBIQD efficiently binds to tubulin ( Kb = 2.03 × 105 M-1 ± 1.88%), inhibits its polymerization, and depolymerizes preformed microtubules (MTs). Low doses of CBIQD have also shown specificity toward tubulin protein in the presence of a nonspecific protein like bovine serum albumin as well as other cytoskeleton component, actin. The in vitro determination of binding site coupled with in silico studies suggests that CBIQD may prefer to occupy the colchicine binding site. Further, CBIQD perturbed tubulin conformation to some extent and protected ∼1.4 cysteine residues toward chemical modification by 5,5'-dithiobis-2-nitrobenzoic acid. We also suggest the possible mechanism underlying CBIQD-induced cancer cell cytotoxicity: CBIQD, when bound to tubulin, may prevent it to maintain a straight conformation; consequently, the α- and ß-heterodimers might be no longer available for MT growth. Thus, the consolidated spectroscopic research described herein explores the potential of CBIQD as a new paradigm in the design and development of novel unfused or nonring-fused naphthalimide-based antimitotic cancer therapeutics in medicinal chemistry research.

Gold­manganese oxide nanocomposite suppresses hypoxia and augments pro-inflammatory cytokines in tumor associated macrophages.

The tumor microenvironment, essentially hypoxic, is sustained by the hypoxia inducing factor (HIF), released from the pro-tumorigenic tumor associated macrophages (TAMs), functionally identical to the M2 phenotype macrophages. Stability of HIF mainly depends on molecular oxygen and an iron-dependent enzyme prolyl hydroxylase, while its activity may be inhibited by high levels of reactive oxygen species and nitric oxide. The present work showcases a novel approach utilizing the anti-tumorigenic potential of a gold-manganese oxide nanocomposite material in the tumor microenvironment that affects tumor hypoxia, exploring the possibility of restoring the immunoregulatory nature of TAMs from their pro-tumorigenic state. Along with the biochemical markers, ELISA and FACS analyses have also confirmed the potential of these nanoparticles in reverting back the M2 phenotype of TAMs to their classically activated M1 phenotype.