Circadian regulation of locomotion, respiration, and arousability in adult blacklegged ticks (Ixodes scapularis).

The blacklegged tick, Ixodes scapularis, is an ectoparasitic arachnid and vector for infectious diseases, including Lyme borreliosis. Here, we investigate the diurnal activity and respiration of wild-caught and lab-reared adult ticks with long-term video recording, multi-animal tracking and high-resolution respirometry. We find male and female ticks are in a more active, more arousable state during circadian night. We find respiration is augmented by light, with dark onset triggering more frequent bouts of discontinuous gas exchange and a higher overall volume of CO2 respired. Observed inactivity during the day meets the criteria of sleep: homeostatic in nature, rapidly reversible, a characteristic pose, and reduced arousal threshold. Our findings indicate that blacklegged ticks are in a distinct, heightened state of activity and arousability during night and in dark, suggesting this period may carry higher risk for tick bites and subsequent contraction of tick-borne diseases.

Probing the interaction and aggregation of lysozyme in presence of organophosphate pesticides: a comprehensive spectroscopic, calorimetric, and in-silico investigation.

Organophosphorus pesticides (OPs) are widely used in agriculture and may contaminate food or water, leading to potential health risks. However, there are few reports on the effect of OPs on protein conformation and aggregation. Hence, in this paper, we have characterized the impact of two OPs, chlorpyrifos (CPF) and methyl parathion (Para), on the model protein HEWL using biophysical and computational methods. The steady-state and time-resolved spectroscopy, Circular dichroism (CD), molecular dynamics simulation, and isothermal titration calorimetry were employed to investigate the binding interactions between HEWL and OPs. The steady-state and time-resolved fluorescence spectroscopy confirm the presence of both static and dynamic quenching between OPs and proteins. Based on fluorescence, MD, and CD results, it was found that the OPs not only show strong binding but also destabilize the protein structure and alter the secondary and tertiary structure of the protein. The molecular docking results showed that OPs entered the binding pocket of the HEWL molecule and interacted through hydrophobic and hydrogen bond interactions. The thermodynamic studies indicated that the binding was spontaneous and OPs have shown an effect on the aggregation process of HEWL. Finally, the protein aggregation process was studied using fluorescence and SDS-PAGE studies in the presence of both the OPs and found to enhance the aggregation process in the presence of OPs. These results provide insights into the potential health risks associated with OPs and highlight the importance of understanding their interactions with biological macromolecules.Communicated by Ramaswamy H. Sarma.

A Comparative Study of Mechanism and Performance of Anionic and Cationic Dialdehyde Nanocelluloses for Dye Adsorption and Separation.

In this study, anionic dialdehyde cellulose (DAC) and cationic dialdehyde cellulose (c-DAC) nanofibrous adsorbents were prepared via a two-step reaction from bamboo pulp, using sodium periodate and Girard's reagent T as oxidizing and cationizing agents, respectively. The performance of DAC and c-DAC for selective dye adsorption and separation was evaluated by six different organic dyes (with varying charge properties) and certain binary mixtures. Both adsorbents could remove the dyes but with different capability, where DAC exhibited high adsorption efficiency against cationic dyes (e.g., the maximum adsorption capacity for Bismarck brown Y was 552.1 mg/g) and c-DAC exhibited high adsorption efficiency against anionic dyes (e.g., the maximum adsorption capacity for Congo red was 540.3 mg/g). To investigate the adsorption mechanism for these adsorbents, effects of contact time, initial pH value, initial dye concentration, and ionic strength on the adsorption activity against Congo red were investigated. The adsorption equilibrium data of DAC were found to fit best with the Langmuir isotherm model, whereas that of c-DAC were found to fit best with the Freundlich model. Both DAC and c-DAC adsorption kinetic data could be described by the pseudo-second-order kinetic model, and these adsorbents possessed stable adsorption efficiency in the pH range of 4-10. Furthermore, their dye adsorption capabilities were found to increase with increasing ionic strength (salt concentration). The distinctive complementary features of DAC and c-DAC will allow them to remove a wide range of organic dyes from industrial wastewater.

Low Fouling Nanostructured Cellulose Membranes for Ultrafiltration in Wastewater Treatment.

Ultrafiltration (UF) is a common technique used in wastewater treatments. However, the issue of membrane fouling in UF can greatly hinder the effectiveness of the treatments. This study demonstrated a low-fouling composite cellulose membrane system based on microfibrillated cellulose (MFC) and silica nanoparticle additives. The incorporation of 'non-spherical' silica nanoparticles was found to exhibit better structural integration in the membrane (i.e., minimal aggregation of silica nanoparticles in the membrane scaffold) as compared to spherical silica. The resulting composite membranes were tested for UF using local wastewater, where the best-performing membrane exhibited higher permeation flux than commercial polyvinylidene difluoride (PVDF) and polyether sulfone (PES) membranes while maintaining a high separation efficiency (~99.6%) and good flux recovery ratio (>90%). The analysis of the fouling behavior using different models suggested that the processes of cake layer formation and pore-constriction were probably two dominant fouling mechanisms, likely due to the presence of humic substances in wastewater. The demonstrated cellulose composite membrane system showed low-fouling and high restoration capability by a simple hydraulic cleaning method due to the super hydrophilic nature of the cellulose scaffold containing silica nanoparticles.

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.

Influence of cyanobacterial inoculants, elevated carbon dioxide, and temperature on plant and soil nitrogen in soybean.

Climate change affects nitrogen dynamics in crops and diazotrophic microorganisms with carbon dioxide (CO2 ) sequestering potential such as cyanobacteria can be promising options. The interactions of three cyanobacterial formulations (Anabaena laxa, Calothrix elenkinii and Anabaena torulosa-Bradyrhizobium japonicum biofilm) on plant and soil nitrogen in soybean, were investigated under elevated CO2 and temperature conditions. Soybean plants were grown inside Open Top Chambers under ambient and elevated (550 ± 25 ppm) CO2 concentrations and elevated temperature (+2.5-2.8°C). Interactive effect of elevated CO2 and cyanobacterial inoculation through A. laxa and Anabaena torulosa-B. japonicum biofilm led to improved growth, yield, nodulation, nitrogen fixation, and seed N in soybean crop. Nitrogenase activity in nodules increased in A. laxa and biofilm treatments, with an increase of 55% and 72%, respectively, over no cyanobacterial inoculation treatment. Although high temperature alone reduced soil microbial biomass carbon, dehydrogenase activity, and soil available N, the combined effect of CO2 and temperature were stimulatory; cyanobacterial inoculation further led to an increase under all the conditions. The highest seed N uptake (758 mg plant-1 ) was recorded with cyanobacterial biofilm inoculation under elevated CO2 with control temperature conditions. The positive interactions of elevated CO2 and cyanobacterial inoculation, particularly through A. laxa and A. torulosa-B. japonicum biofilm inoculation highlights their potential in counteracting the negative impact of changing climate along with enhancing plant and soil N in soybean.

Lipase production from mutagenic strain of Fusarium Incarnatum KU377454 and its immobilization using Au@Ag core shells nanoparticles for application in waste cooking oil degradation.

In the present study, lipase production from mutated strain of Fusarium incarnatum KU377454 was optimized through central composite design (CCD) based response surface methodology (RSM). The maximum lipase production (4.01 IU/mL) was obtained within 4 days of incubation using 0.1% CaCl2 concentration and 8% wheat bran concentration. Further, salting out technique was applied for partial purification of lipase. The partially purified lipase was immobilized using Au@Ag bimetallic nanoshell. The characterization of immobilized lipase was carried out by transmission electron microscopy (TEM), field emission scanning electron microscopy (FE-SEM), Fourier transformed infrared (FTIR), energy dispersive X-ray (EDX), X-ray diffraction (XRD) and thermo gravimetric analysis (TGA). The immobilized lipase could retain its 95% of activity after 15 days of storage at 4 °C. Subsequently, Au@Ag immobilized lipase was used for the degradation of waste cooking oil (WCO), which showed higher WCO degradation (85%) compared to the free lipase mediated waste cooking oil degradation (71%). The immobilized lipase could be reused for five times without any loss of its activity.

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.

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.

A Chalcone-Based Potential Therapeutic Small Molecule That Binds to Subdomain IIA in HSA Precisely Controls the Rotamerization of Trp-214.

The principal intent of this work is to explore whether the site-specific binding of a newly synthesized quinoline-appended anthracenyl chalcone, (E)-3-(anthracen-10-yl)-1-(6,8-dibromo-2-methylquinolin-3-yl)prop-2-en-1-one (ADMQ), with an extracellular protein of the human circulatory system, human serum albumin (HSA), can control the rotamerization of its sole tryptophan residue, Trp-214. With this aim, we have systematically studied the binding affinity, interactions, and localization pattern of the title compound inside the specific binding domain of the transport protein and any conformation alteration caused therein. Multiple spectroscopic experiments substantiated by an in silico molecular modeling exercise provide evidence for the binding of the guest ADMQ in the hydrophobic domain of HSA, which is primarily constituted by residues Trp-214, Arg-218, Arg-222, Asp-451, and Tyr-452. Rotationally restricted ADMQ prefers to reside in Sudlow site I (subdomain IIA) of HSA in close proximity (2.45 nm) to the intrinsic fluorophore Trp-214 and is interestingly found to control its vital rotamerization process. The driving force for this rotational interconversion is predominantly found to be governed by the direct interaction of ADMQ with Trp-214. However, the role of induced conformational perturbation in the biomacromolecule itself upon ADMQ adoption cannot be ruled out completely, as indicated by circular dichroism, 3D fluorescence, root-mean-square deviation, root-mean-square fluctuation, and secondary structure element observations. The comprehensive spectroscopic study outlined herein provides important information on the biophysical interaction of a chalcone-based potential therapeutic candidate with a carrier protein, exemplifying its utility in having a regulatory effect on the microconformations of Trp-214.

Is the Sudlow site I of human serum albumin more generous to adopt prospective anti-cancer bioorganic compound than that of bovine: A combined spectroscopic and docking simulation approach.

A comparative biophysical study on the individual conformational adaptation embraced by two homologous serum albumins (SA) (bovine and human) towards a potential anticancer bioorganic compound 2-(6-chlorobenzo[d] thiazol-2-yl)-1H-benzo[de] isoquinoline-1,3(2H)- dione (CBIQD) is apparent from the discrimination in binding behavior and the ensuing consequences accomplished by combined in vitro optical spectroscopy, in silico molecular docking and molecular dynamics (MD) simulation. The Sudlow site I of HSA although anion receptive, harbors neutral CBIQD in Sudlow site I (subdomain IIA, close to Trp) of HSA, while in BSA its prefers to snugly fit into Sudlow site II (subdomain IIIA, close to Tyr). Based on discernable diminution of HSA mean fluorescence lifetime as a function of biluminophore concentration, facile occurrence of fluorescence resonance energy transfer (FRET) is substantiated as the probable quenching mechanism accompanied by structural deformations in the protein ensemble. CBIQD establishes itself within HSA close to Trp214, and consequently reduces the micropolarity of the cybotactic environment that is predominantly constituted by hydrophobic amino acid residues. The stronger association of CBIQD with HSA encourages an allosteric modulation leading to slight deformation in its secondary structure whereas for BSA the association is comparatively weaker. Sudlow site I of HSA is capable to embrace a favorable conformation like malleable gold to provide room for incoming CBIQD, whereas for BSA it behaves more like rigid cast-iron which does not admit any change thus forcing CBIQD to occupy an altogether different binding location i.e. the Sudlow site II. The anticancer CBIQD is found to be stable within the HSA scaffold as vindicated by root mean square deviation (RMSD) and root mean square fluctuation (RMSF) obtained by MD simulation. A competitively inhibited esterase-like activity of HSA upon CBIQD binding to Lys199 and Arg257 residues, plausibly envisions that similar naphthalimide based prodrugs, bearing ester functionality, can be particularly activated by Sudlow site I of HSA. The consolidated spectroscopic research described herein may encourage design of naphthalimide based pro-drugs for effective in vivo biodistribution using HSA-based drug delivery systems.

A Simple Approach to Prepare Carboxycellulose Nanofibers from Untreated Biomass.

A simple approach was developed to prepare carboxycellulose nanofibers directly from untreated biomass using nitric acid or nitric acid-sodium nitrite mixtures. Experiments indicated that this approach greatly reduced the need for multichemicals, and offered significant benefits in lowering the consumption of water and electric energy, when compared with conventional multiple-step processes at bench scale (e.g., TEMPO oxidation). Additionally, the effluent produced by this approach could be efficaciously neutralized using base to produce nitrogen-rich salts as fertilizers. TEM measurements of resulting nanofibers from different biomasses, possessed dimensions in the range of 190-370 and 4-5 nm, having PDI = 0.29-0.38. These nanofibers exhibited lower crystallinity than untreated jute fibers as determined by TEM diffraction, WAXD and 13C CPMAS NMR (e.g., WAXD crystallinity index was ∼35% for nanofibers vs 62% for jute). Nanofibers with low crystallinity were found to be effective for removal of heavy metal ions for drinking water purification.

Development of multifunctional heterocyclic Schiff base as a potential metal chelator: a comprehensive spectroscopic approach towards drug discovery.

Amyloid-ß peptides and their metal-associated aggregated states have been implicated in the pathogenesis of Alzheimer's disease. The present paper epitomises the design and synthesis of a small, neutral, lipophilic benzothiazole Schiff base (E)-2-((6-chlorobenzo[d]thiazol-2-ylimino)methyl)-5-diethylamino)phenol (CBMDP), and explores its multifunctionalty as a potential metal chelator/fluorophore using UV-visible absorption, steady-state fluorescence, single molecule fluorescence correlation spectroscopic (FCS) techniques which is further corroborated by in silico studies. Some pharmaceutically relevant properties of the synthesized compound have also been calculated theoretically. Steady-state fluorescence and single molecule FCS reveal that the synthesized CBMDP not only recognizes oligomeric Aß40, but could also be used as an amyloid-specific extrinsic fluorophore as it shows tremendous increase in its emission intensity in the presence of Aß40. Molecular docking exercise and MD simulation reveal that CBMDP localizes itself in the crucial amyloidogenic and copper-binding region of Aß40 and undergoes a strong binding interaction via H-bonding and π-π stacking. It stabilizes the solitary α-helical Aß40 monomer by retaining the initial conformation of the Aß central helix and mostly interacts with the hydrophilic N-terminus and the α-helical region spanning from Ala-2 to Val-24. CBMDP exhibits strong copper as well as zinc chelation ability and retards the rapid copper-induced aggregation of amyloid peptide. In addition, CBMDP shows radical scavenging activity which enriches its functionality. Overall, the consolidated in vitro and in silico results obtained for the synthesized molecule could provide a rational template for developing new multifunctional agents.

Conformation controlled turn on-turn off phosphorescence in a metal-free biluminophore: thriving the paradox that exists for organic compounds.

The legacy of phosphorescence from expensive organometallic compounds has inspired researchers to develop efficient metal-free organic phosphors. Although organic phosphors offer a cheaper alternative, the long-lived triplets of organic phosphors that are primarily consumed by vibrational dissipation need to be adequately suppressed, and this provides an opportunity to design new organic entities, at par with the organometallic compounds, based on conformational control and incorporation of useful functional groups to alter their emissive properties, especially phosphorescence. Here, we have achieved a proficient dual state emission, underlining the key design rule of conformational control in an organic molecular platform for 2-(6-chlorobenzo[d]thiazol-2-yl)-1H-benzo[de]isoquinoline-1,3(2H)-dione (CBIQD). In contrast to other known naphthalimides, the system limiting access to non-radiative triplet states is achieved by steric encumbrance which exhibits strong phosphorescence. Here, in addition to strong fluorescence (from planar conformer), phosphorescence is unlocked by suppression of non-radiative channels from the non-planar conformer in glassy solvents (77 K) and when embedded in a polymer matrix of poly(methyl methacrylate) (PMMA) at RT. The spectroscopic delineation of adopted geometry and optical property relationship is sought by a steric approach, extent of intramolecular charge transfer (ICT), presence of carbonyl groups, directed heavy atom effect and the spin-orbit coupling (SOC) invoked by -S- and -Cl atoms. Time dependent density functional theory (TD-DFT) is used to explain the favourable mechanistic path for the decay of excited states (ESs) leading to phosphorescence from a non-planar conformer and fluorescence from a planar conformer. The spectacular access to the radiative singlet and triplet states suggests that there is less scope for loss channels. The phosphorescence of the CBIQD-PMMA system may find use in other biomedical applications due to the biocompatibility of each component.

Design, Synthesis, and Proticity Inclined Conformational Modulation in a Highly Fluorescent Bichromophoric Naphthalimide Derivative: Hint Directed from RICT Perspective.

The present study embodies design, in silico DNA interaction, synthesis of benzothiazole containing naphthalimide derivative, 2-(6-chlorobenzo[d]thiazol-2-yl)-1H-benzo[de] isoquinoline-1,3(2H)-dione (CBIQD) along with its systematic photophysics, solvatochromic behavior, and solvation dynamics using an experimental and theoretical spectroscopic approach. Steady-state dual emission and biexponential fluorescence decay reveals the formation of two different excited species. Ground- and excited-state optimized geometry and the potential-energy curve obtained from DFT and TD-DFT calculation ascertained the existence of nonplanar and planar conformation. When the solvent polarity is changed from nonpolar to protic polar, the feebly emissive emission band highly intensifies probably due to the reversal of n, π*-π, π* emissive state along with consequent modulation of their energy gap that is induced by H-bonding. Excluding nonpolar solvents, in all other solvents, the Stokes shift correlates linearly with orientation polarizability, whereas in water, the story remains intriguing. With photoexcitation, intermolecular H-bonding stimulates the pyramidalization tendency of imide "N" with subsequent conformational change of GS nonplanar geometry to a coplanar one through acceptor rehybridization generating a rehybridized intramolecular charge transfer (RICT) state that caused a dramatic fluorescence upsurge. This allosteric modulation is promoted by excited-state H-bonding dynamics especially in strong H-bond donor water. A close interplay between preferential solvation and the proximity effect is evident in the emission behavior in a benzene (Bn)-ethanol (EtOH) binary mixture. Molecular docking analysis delineates considerable noncovalent sandwiched π-π stacking interactions of CBIQD with the pyrimidine rings as well as with imidazole rings of dG 6 and dG 2 base pairs of B-DNA double helix, which probably suffices the design strategy adopted. Overall, a strategic design to synthesize a highly fluorescent and potential bioactive agent is executed to revolutionize the fluorophore field due its enormous progressive importance in biochemical applications.

Groove binding mediated structural modulation and DNA cleavage by quinoline appended chalcone derivative.

The present study embodies the detail DNA binding interaction of a potential bioactive quinoline appended chalcone derivative (E)-3-(anthracen-10-yl)-1-(6,8-dibromo-2-methylquinolin-3-yl)prop-2-en-1-one (ADMQ) with calf thymus DNA (ctDNA) and its consequences by UV-Vis absorption, steady state fluorescence spectroscopy, fluorescence anisotropy, circular dichromism, helix melting, agarose gel electrophoresis, molecular docking, Induced Fit Docking (IFD) and molecular dynamics (MD) simulation. The UV-Vis absorption and fluorescence study reveal that the molecule undergoes considerable interaction with the nucleic acid. The control KI quenching experiment shows the lesser accessibility of ADMQ molecule to the ionic quencher (I(-)) in presence of ctDNA as compared to the bulk aqueous phase. Insignificant change in helix melting temperature as well as in circular dichromism (CD) spectra points toward non-covalent groove binding interaction. The moderate rotational confinement of this chalcone derivative (anisotropy=0.106) trapped in the nucleic acid environment, the comparative displacement assay with well-known minor groove binder Hoechst 33258 and intercalator Ethidium Bromide establishes the minor groove binding interactions of the probe molecule. Molecular docking, IFD and MD simulation reveal that the DNA undergoes prominent morphological changes in terms of helix unwinding and bending to accommodate ADMQ in a crescent shape at an angle of 110° in a sequence specific manner. During interaction, ADMQ rigidifies and bends the sugar phosphate backbone of the nucleic acid and thereby shortens its overall length by 3.02Å. Agarose gel electrophoresis experiment with plasmid pBR 322 reveals that the groove binded ADMQ result in a concentration dependent cleavage of plasmid DNA into its supercoiled and nicked circular form. The consolidated spectroscopic research described herein provides quantitative insight into the interaction of a heterocyclic chalcone derivative with relevant target nucleic acid, which may be useful for the future research on chalcone based therapeutic agents.

Design, synthesis, physicochemical studies, solvation, and DNA damage of quinoline-appended chalcone derivative: comprehensive spectroscopic approach toward drug discovery.

The present study epitomizes the design, synthesis, photophysics, solvation, and interaction with calf-thymus DNA of a potential antitumor, anticancer quinoline-appended chalcone derivative, (E)-3-(anthracen-10-yl)-1-(6,8-dibromo-2-methylquinolin-3-yl)prop-2-en-1-one (ADMQ) using steady state absorption and fluorescence spectroscopy, molecular modeling, molecular docking, Fourier-transform infrared spectroscopy (FTIR), molecular dynamics (MD) simulation, and gel electrophoresis studies. ADMQ shows an unusual photophysical behavior in a variety of solvents of different polarity. The dual emission has been observed along with the formation of twisted intramolecular charge transfer (TICT) excited state. The radiationless deactivation of the TICT state is found to be promoted strongly by hydrogen bonding. Quantum mechanical (DFT, TDDFT, and ZINDO-CI) calculations show that the ADMQ is sort of molecular rotor which undergoes intramolecular twist followed by a complete charge transfer in the optimized excited state. FTIR studies reveals that ADMQ undergoes important structural change from its native structure to a ß-hydroxy keto form in water at physiological pH. The concentration-dependent DNA cleavage has been identified in agarose gel DNA electrophoresis experiment and has been further supported by MD simulation. ADMQ forms hydrogen bond with the deoxyribose sugar attached with the nucleobase adenine DA-17 (chain A) and result in significant structural changes which potentially cleave DNA double helix. The compound does not exhibit any deleterious effect or toxicity to the E. coli strain in cytotoxicity studies. The consolidated spectroscopic research described herein can provide enormous information to open up new avenues for designing and synthesizing chalcone derivatives with low systematic toxicity for medicinal chemistry research.