Ground State Complex Formation Research Articles

Selective detection of azelnidipine in pharmaceuticals via carbon dot mediated spectrofluorimetric method: A green approach.

A spectrofluorimetric method using fluorescent carbon dots (CDs) was developed for the selective detection of azelnidipine (AZEL) pharmaceutical in the presence of other drugs. In this study, N-doped CDs (N-CDs) were synthesized through a single-step hydrothermal process, using citric acid and urea as precursor materials. The prepared N-CDs showed a highly intense blue fluorescence emission at 447 nm, with a photoluminescence quantum yield of ~21.15% and a fluorescence lifetime of 0.47 ns. The N-CDs showed selective fluorescence quenching in the presence of all three antihypertensive drugs, which was used as a successful detection platform for the analysis of AZEL. The photophysical properties, UV-vis light absorbance, fluorescence emission, and lifetime measurements support the interaction between N-CDs and AZEL, leading to fluorescence quenching of N-CDs as a result of ground-state complex formation followed by a static fluorescence quenching phenomenon. The detection platform showed linearity in the range 10-200 μg/ml (R2 = 0.9837). The developed method was effectively utilized for the quantitative analysis of AZEL in commercially available pharmaceutical tablets, yielding results that closely align with those obtained from the standard method (UV spectroscopy). With a score of 0.76 on the 'Analytical GREEnness (AGREE)' scale, the developed analytical method, incorporating 12 distinct green analytical chemistry components, stands out as an important technique for estimating AZEL.

Comparative study on interactions of phillyrin and phillygenol with lysozyme: Spectroscopy, differential scanning calorimetry and molecular modeling approaches

Phillyrin (PR) and its derivative phillygenol (PG) are major active extracts of the Chinese medicine Forsythiae Fructus. Lysozyme, an important carrier protein, has a variety of physiological along with pharmaceutical functions. Herein, the interactions of PR and PG with hen egg white lysozyme (HEWL) are investigated in details by spectroscopic analyses, differential scanning calorimetry (DSC) tests, and molecular modeling approaches. Fluorescence measurement and UV–visible absorption difference spectroscopy reveal that an “untypical static quenching” takes place pointing towards the formation of ground state complex. The binding constants of HEWL-PG are greater than that of HEWL-PR. Moreover, the major driving force for the binding process is elucidated as hydrophobic interactions for both cases. Circular dichroism spectroscopy and three-dimensional fluorescence indicate that PR and PG decrease the helical structure of the HEWL and hydrophobicity surrounding Trp and Tyr residues. The thermal stability of HEWL decreases in the presence of PR and PG by DSC. Docking study infers that both PR and PG could bind to the hydrophobic cavity of HEWL and supports the higher binding of PG than PR. Molecular dynamics study illustrates that PR has higher relative position change, which may attribute to its lower binding ability. In terms of the radius of gyration (Rg), PG causes the protein structure to swell even more. The average hydrogen bonds number of HEWL-PG is less than that of HEWL-PR and more changes of the residual fluctuation are observed in HEWL-PG system. Furthermore, MM-PBSA analysis exhibits that HEWL-PG has lower binding energy. Collectively, these results support that both PR and PG could bind to HEWL, but PG possesses higher affinity which leads to stronger secondary structural changes of HEWL than PR. These findings are beneficial to comprehensively understand the binding characteristic of PR and PG with HEWL, providing experimental basis for pharmacokenitics of PR and PG.

Imidazolium-Functionalized Conjugated Polymer for On-Site Visual and Ultrasensitive Detection of Toxic Hexavalent Chromium.

Hexavalent chromium [Cr(VI)] is considered a serious environmental pollutant that possesses a hazardous effect on humans even at low concentrations. Thus, the development of a bifunctional material for ultratrace-selective detection and effective elimination of Cr(VI) from the environment remains highly desirable and scarcely reported. In this work, we explore an imidazolium-appended polyfluorene derivative PF-DBT-Im as a highly sensitive/selective optical probe and a smart adsorbent for Cr(VI) ions with an ultralow detection limit of 1.77 nM and removal efficiency up to 93.7%. In an aqueous medium, PF-DBT-Im displays obvious transformation in its emission color from blue to magenta on exclusively introducing Cr(VI), facilitating naked-eye colorimetric detection. Consequently, a portable sensory device integrated with a smartphone is fabricated for realizing real-time and on-site visual detection of Cr(VI). Besides, the imidazolium groups attached onto side chains of PF-DBT-Im are found to be highly beneficial for achieving selective and efficient elimination of Cr(VI) with capacity as high as 128.71 mg g-1. More interestingly, PF-DBT-Im could be easily regenerated following treatment with KBr and can be recycled at least five times in a row. The main factor behind ultrasensitive response and excellent removal efficiency is found to be anion-exchange-induced formation of a unique ground-state complex between PF-DBT-Im and Cr(VI), as evident by FT-IR, XPS, and simulation studies. Thus, taking advantage of the excellent signal amplification property and rich ion-exchange sites, a dual-functional-conjugated polymer PF-DBT-Im is presented for the concurrent recognition and elimination of Cr(VI) ions proficiently and promptly with great prospects in environmental monitoring and water decontamination.

Interaction of eugenol-based anti-tuberculosis nanoemulsion with bovine serum albumin: A spectroscopic study including Rifampicin, Isoniazid, Pyrazinamide, and Ethambutol

Tuberculosis (TB), a deadly infectious disease, is primarily caused by the bacterium Mycobacterium tuberculosis. The misuse of antibiotics has led to the development of drug resistance, prompting researchers to explore new technologies to combat multidrug-resistant Tuberculosis (MDR TB). Phospholipid-based nanotherapeutics, such as nanoemulsions, are gaining traction as they enhance drug solubility, stability, and bioavailability. Our study focuses on the interaction between Bovine Serum Albumin (BSA) and a drug-loaded nanoemulsion based on Eugenol. This nanoemulsion incorporates Eugenol, Clove, cinnamon oil, and first-line anti-tuberculosis drugs like Rifampicin, Isoniazid, Pyrazinamide, and Ethambutol. The primary objective is to assess the biosafety profile of the nanoemulsion upon interaction with BSA. We employed Fluorescence, UV–visible, and Fourier Transform Infrared Spectroscopy (FTIR) to analyze this interaction.UV–visible spectroscopy detected changes in hydrophobicity due to structural alterations in BSA near the tryptophan residue, leading to the formation of ground-state complexes. Fluorescence spectroscopy demonstrated that the nanoemulsion effectively quenched fluorescence originating from tryptophan and tyrosine residues. Studies using synchronous and three-dimensional spectroscopy point to a potential modification of the aromatic environment of BSA by the nanoemulsion. Resonance light scattering spectra indicated the formation of large aggregates due to the interaction with the nanoemulsion. The second derivative FTIR spectra showed an increase in the magnitude of secondary structure bands, suggesting a conformational shift. This research has significant pharmacological implications for developing safer, more targeted drug delivery systems. The information obtained from the interaction of the nanoemulsion with the blood carrier protein is vital for the future development of superior carriers with minimal adverse effects on patients. It is crucial to remember that conformational changes brought on by drug-ligand complexes attaching to carrier proteins may have negative consequences. Therefore, this study enhances the in vitro evaluation of potential adverse effects of the nanoemulsion on serum proteins.

Possible Role of High-Molecular-Weight Salivary Proteins in Astringency Development.

Since the initial findings that food tannin/salivary protein interaction and subsequent precipitation is the main cause of the astringency development, numerous studies have concentrated on the supramolecular characterization of these bindings. Most of these works have focused on the low-molecular-weight salivary proteins, in particular proline-rich proteins, hardly considering the involvement of the high-molecular-weight salivary proteins (HMWSPs). Herein, different techniques such as fluorescence quenching, Isothermal Titration Calorimetry and HPLC-MS-DAD were employed to determine the occurrence of molecular interactions between three HMWSPs, namely, mucin, α-amylase and albumin, and a complex extract of tannins composed mainly of flavan-3-ols. The obtained results prove the capability of the three HMWSPs to effectively interact with the flavan-3-ol extract, involving different forces and action mechanisms. Flavan-3-ols are capable of interacting with mucins by a mechanism that includes the formation of stable ground-state complexes that led to approximately 90% flavan-3-ol precipitation, while for albumin and α-amylase, the interaction model of a "sphere of action" was established, which represented only 20% flavan-3-ol precipitation. These data highlight the relevance of including HMWSPs in astringency analyses, paying special heed to the role of mucins in the interaction and subsequent precipitation of dietary tannins.

Controlled photoinduced electron transfer via triplet in polymer matrix using electrostatic interactions

Drawing inspiration from highly efficient natural photosynthetic systems, we developed an artificial photoinduced electron transfer (PET) system within a poly(N-methyl-4-vinylpyridinium) (P4VPMe) polymer matrix. This system features 5,10,15,20-tetrakis-(4-sulfonatophenyl) porphyrin (TPPS) and its zinc complex (ZnTPPS) as electron donors and methylviologen (MV2+) as the electron acceptor. In the presence of an excess of P4VPMe, ZnTPPS exists as individual molecules rather than self-aggregating, favoring PET. Under these conditions, P4VPMe inhibits the formation of ground-state charge-transfer complex between ZnTPPS and MV2+. This shifts the main PET process from singlet to triplet states. ZnTPPS in an excess of P4VPMe demonstrates over a tenfold increase in catalytic activity for the photoinduced oxidation of MV2+ compared to ZnTPPS alone.

Deciphering the intriguing molecular recognition of a novel indene-phloroglucinol tethered compound with human serum albumin using multi-spectroscopy and molecular docking studies

A new indene-phloroglucinol tethered compound IPC1 was synthesized in our laboratory in three steps. The interaction of the final compound IPC1 with human serum albumin (HSA) was studied using multi-spectroscopic and molecular docking methods. UV–vis and fluorescence studies confirmed the spontaneous formation of ground state complex and the values of the binding constants were found to be in the order of 104 M−1 (4.727×104 M−1 at 290.15 K). Positive ΔS° (+112.797 J K−1 mol−1) and ΔH° (+6.756 KJ mol−1) indicate the involvement of hydrophobic interaction as the major contributing force in the complex formation process. Site marker studies suggested that the compound IPC1 binds near the subdomain IIIA of HSA, which was further supported by fluorescence spectroscopic and molecular docking analysis.

Dynamics of interfacial charge transfer between CsPbBr3 perovskite nanocrystals and molecular acceptors for photodetection application

Perovskite nanocrystals (NCs) recently emerged as a suitable candidate for optoelectronic applications because of its simplistic synthesis approach and superior optical properties. For better device performance, the effective absorption of incident photons and the understanding of charge transfer (CT) process are the basic requirements. Herein, we investigate the interfacial charge transfer dynamics of CsPbBr3 NCs in the presence of different molecular acceptors; 7,7,8,8-Tetracyanoquinodimethane (TCNQ) and 11,11,12,12 tetracyanonaphtho-2,6-quinodimethane (TCNAQ). The vivid change in CT dynamics at the interfaces of NCs and two different molecular acceptors (TCNQ and TCNAQ) has been observed. The results demonstrate that the ground state complex formation in the presence of TCNQ acts as additional driving force to accelerate the charge transfer between the NCs and molecular acceptor. Moreover, this donor (NCs)-acceptor (TCNQ, TCNAQ) system results in the higher absorption of incident photons. Finally, the photo detector based on CsPbBr3-TCNQ system was fabricated for the first time. The device exhibited a high on–off ratio (104). Furthermore, the CsPbBr3-TCNQ photodetector shows a fast photoresponse times of 180 ms/110 ms (rise/decay time) with a specific detectivity (D*) of 5.2 × 1011 Jones. The simple synthesis and outstanding photodetection abilities of this perovskite NCs-molecular acceptor system make them potential candidates for optoelectronic applications.

Investigating the binding of caffeic acid to human hemoglobin using multispectroscopic and molecular docking approaches

Caffeic acid (CA) is a hydroxycinnamic acid derivative that possess a wide variety of biological properties and is non-toxic to humans. The binding mechanism of CA with human hemoglobin (HHb) was studied for the first time using multispectroscopic and molecular docking methods. The UV–visible absorption spectra showed that CA interacts with HHb through the formation of ground state complex. The fluorescence studies revealed that CA quenches HHb fluorescence by the static mechanism and confirmed the presence of a single CA binding site on the HHb molecule. The negative values of thermodynamics parameters (ΔH,ΔSand ΔG) showed that the binding of CA to HHb is a spontaneous and exothermic process. Hydrogen bonds and van der Waal interactions are the major intermolecular forces that stabilize the HHb-CA complex. Synchronous fluorescence experiments showed that binding of CA altered the microenvironment around tryptophan residues of HHb. Fluorescence resonance energy transfer studies indicated a high propensity of energy transfer from tryptophan residues of HHb to CA. Circular dichroism spectra and catalytic esterase activity confirmed that only minor changes occur in the secondary structure of HHb in the presence of CA. Molecular docking study identified the HHb amino acid residues involved in binding to CA. Analysis of the binding mode of CA with HHb represents an important step in elucidating the molecular mechanism of the protection of HHb from oxidative damage. This will help in understanding the potential role of CA and related antioxidants as therapeutic agents in various blood-related diseases.

Pt(II) Tetrafacial Barrel with Aggregation-Induced Emission for Sensing.

A new tetraphenylpyrazine-based tetraimidazole ligand (L) was synthesized and used for subcomponent self-assembly with cis-(tmeda)Pd(NO3)2 and cis-Pt(PEt3)2(OTf)2, leading to the formation of two tetrafacial barrels [Pd8L4(tmeda)8](NO3)16 (1) and [Pt8L4(PEt3)16](OTf)16 (2), respectively. Although ligand L is aggregation-induced emission (AIE) active, barrel 2 showed a magnificently higher AIE activity than ligand L, while 1 failed to retain the AIE properties of the ligand. Pd(II) barrel 1, undergoing an aggregation-caused quenching (ACQ) phenomenon, nullified the AIE activity of the ligand to be used in the photophysical application. The enhanced emission in the aggregated state of Pt(II) barrel 2 was used for the recognition of picric acid (PA), which is explosive in nature and one of the groundwater contaminants in landmine areas. The recognition of picric acid was found to be selective in comparison with that of other nitroaromatic compounds (NACs), which could be attributed to ground-state complex formation and resonance energy transfer between picric acid and barrel 2. The use of new AIE-active assembly 2 for selective detection of PA with a low detection limit is noteworthy.

A red emissive covalently bonded graphene quantum dot-Tetraaminophenylporphyrin hybrid as a probe for the sensing of L-proline

L-Proline, the exclusive secondary amino acid with proteinogenic properties, is a vital contributor to body metabolism and the maintenance of muscle repairs, playing a pivotal role in numerous physiological processes in the human body. However, the current understanding of proline sensing is limited. In this study, we have used Tetraaminophenylporphyrin (TAPP) covalently functionalized graphene quantum dot (GQD) as a probe for the selective and sensitive detection of L-Proline. Analytical studies carried out under the optimized conditions reveal a good linear range of 9.8×10−5 M to 3.5×10−3 M with 1.6×10−7 M limit of detection. Photophysical studies reveal a ground state complex formation between the probe and proline which is responsible for the turn-off behaviour. This is not present in the case of the individual components GQD and TAPP separately which highlights the importance of covalent functionalization. The stabilization energy of the complex between the probe and different aminoacids and the corresponding hydrogen bond distances between these two moieties were calculated theoretically using density functional theory. This corroborates the enhanced stability of complex formation and the selectivity of probe towards proline compared to other aminoacids. The practical utility of the developed probe for the detection of proline in real samples like commercial milk and artificial urine is also demonstrated by spike recovery analysis which results in a recovery percent and RSD values within the acceptable limit.

Studies on the interaction of 2,4-dibromophenol with human hemoglobin using multi-spectroscopic, molecular docking and molecular dynamics techniques

2,4-Dibromophenol (DBP) has several industrial applications, including as a wood preservative and flame retardant. This study investigated the interaction between DBP and human hemoglobin (Hb) using spectroscopic, molecular docking and molecular dynamic techniques. The UV-visible spectra showed ground-state complex formation between DBP and Hb. Fluorescence studies revealed that DBP binding caused significant quenching of Hb fluorescence by the static quenching mechanism. The binding of DBP to Hb is a spontaneous process that involves van der Waals forces and hydrogen bonds. There is one DBP binding site on each Hb molecule that is located at the α1β2 interface of Hb. DBP binding did not alter the microenvironment of tyrosine and tryptophan residues in Hb. Circular dichroism studies revealed that DBP increased the α-helical content of Hb. The intrinsic esterase activity of Hb was inhibited by DBP in a concentration-dependent manner. Molecular docking showed that DBP binds to Hb via hydrogen bonds, hydrophobic, van der Waals and interactions. Molecular dynamics simulation confirmed that the Hb-DBP complex is stable. Overall, the results of this study clearly show that DBP induces structural changes and interferes with the function of Hb. This can have important implications for human health. Communicated by Ramaswamy H. Sarma

Hydroxychloroquine-Loaded Chitosan Nanoparticles Induce Anticancer Activity in A549 Lung Cancer Cells: Design, BSA Binding, Molecular Docking, Mechanistic, and Biological Evaluation.

The current study describes the encapsulation of hydroxychloroquine, widely used in traditional medicine due to its diverse pharmacological and medicinal uses, in chitosan nanoparticles (CNPs). This work aims to combine the HCQ drug with CS NPs to generate a novel nanocomposite with improved characteristics and bioavailability. HCQ@CS NPs are roughly shaped like roadways and have a smooth surface with an average size of 159.3 ± 7.1 nm, a PDI of 0.224 ± 0.101, and a zeta potential of +46.6 ± 0.8 mV. To aid in the development of pharmaceutical systems for use in cancer therapy, the binding mechanism and affinity of the interaction between HCQ and HCQ@CS NPs and BSA were examined using stopped-flow and other spectroscopic approaches, supplemented by molecular docking analysis. HCQ and HCQ@CS NPs binding with BSA is driven by a ground-state complex formation that may be accompanied by a non-radiative energy transfer process, and binding constants indicate that HCQ@CS NPs-BSA was more stable than HCQ-BSA. The stopped-flow analysis demonstrated that, in addition to increasing BSA affinity, the nanoformulation HCQ@CS NPS changes the binding process and may open new routes for interaction. Docking experiments verified the development of the HCQ-BSA complex, with HCQ binding to site I on the BSA structure, primarily with the amino acids, Thr 578, Gln 579, Gln 525, Tyr 400, and Asn 404. Furthermore, the nanoformulation HCQ@CS NPS not only increased cytotoxicity against the A549 lung cancer cell line (IC50 = 28.57 ± 1.72 μg/mL) compared to HCQ (102.21 ± 0.67 μg/mL), but also exhibited higher antibacterial activity against both Gram-positive and Gram-negative bacteria when compared to HCQ and chloramphenicol, which is in agreement with the binding constants. The nanoformulation developed in this study may offer a viable therapy option for A549 lung cancer.

Binding interactions of Vildagliptin with pepsin: A multi-spectroscopic and in-silico approach and a comparative account with metformin

Vildagliptin (VDG) and Metformin (Met) belong to a class of dipeptidylpeptidase-4 (DPP-4) inhibitor and biguanide, respectively and used for the management of diabetes mellitus type II (DMTII). Both the drugs are orally available which leads to various side effects due to its oral ingestion. Occurrence of these side effects might be due to some interactions with pepsin at a molecular level. Therefore, in order to investigate these interactions, multi-spectroscopic and in-silico techniques have been extensively studied to identify the binding characteristics of VDG with pepsin. Fluorescence data suggested that the quenching is due to dynamic and static mechanism and static was dominant one. However, fluorescence and UV–Vis spectroscopic measurement analysis suggested that VDG tends to associate with pepsin, via ground-state complex formation. Fluorescence study revealed the binding-constant value which was found to be 0.559 × 103 M−1 at 298.15 K that is non-covalent in nature. VDG-pepsin complex shows exothermic and spontaneous binding as confirmed by the calculated values of ΔH, ΔS, and ΔG, are majorly caused by van der Waals forces and H-bonding interactions. CD spectra of pepsin in presence of VDG confirmed post binding conformational change. Enzyme-activity assay showed that activity of pepsin was decreased by upto 28 %. FRET analysis suggested that energy transfer efficiency is negligible for VDG-pepsin interaction. In-silico analysis reveals that H-bonding and electrostatic negative forces are the significant driving forces involved in the interaction of VDG and pepsin.

Exploring the effect of a series of flavonoids on tyrosinase using integrated enzyme kinetics, multispectroscopic, and molecular modelling analyses

The control of food browning can be achieved by inhibiting tyrosinase (TY) activity, but current studies on the interaction of flavonoids as potent inhibitors with TY are inadequate. Herein, the effect of a library of flavonoids on TY was investigated using enzyme kinetics, multispectroscopic methods, and molecular modelling. Some flavonoids including 4, 8, 10, 17, 18, 28, 30, 33, and 34 exhibited potent TY inhibitory activity, with compound 10 demonstrating reversible inhibition in a mixed-competitive manner. Ultraviolet-visible spectral changes confirmed the formation of flavonoid-TY complexes. Fluorescence quenching analysis suggested effective intrinsic fluorescence quenching by flavonoids through static quenching with the ground-state complex formation. Synchronous fluorescence spectra showed the microenvironment change around the fluorophores induced by flavonoids. ANS-binding fluorescence assay indicated TY's surface hydrophobicity change by flavonoids and highlighted the change in secondary structure conformation, which was further confirmed by Fourier-transform infrared spectra. Molecular modelling results helped visualize the preferred binding conformation at the active site of TY, and demonstrated the important role of hydrophobic interaction and hydrogen bonding in stabilizing the flavonoid-TY complexes. These findings prove that diverse flavonoid structures distinctly impact their binding behavior on TY and contribute to understanding flavonoids' potential as TY inhibitors in controlling food browning.

3D Ag(I) coordination polymer sandwiched by water-muconate anionic layers: Synthesis, structure, Hirshfeld surface analysis, binding with BSA, and photocatalytic activity

The sonochemical reaction between silver salt, 1,3-bis(4-pyridylpropane (bpp) and trans,trans-muconic acid (H2muc) formed an Ag(I) coordination polymer with a 3D supramolecular sandwich architecture, {[Ag8(bpp)8(H2O)3].(muc)4.29(H2O)}n, (1) consisting of the silver-bpp cationic host that alternates with 2D water–muc guest anionic layers. The latter is formed by H-bonded water molecules-anions comprising hexagonal (H2O)6 clusters. The Hirshfeld surface and fingerprint plots have been used to quantify the weak intermolecular interactions in the crystal packing arrangement. The study showed that intermolecular hydrogen bonds are the most critical in constructing the titled supramolecular complex, accounting for 51.2% of the total Hirshfeld surface. Several spectrofluorimetric methods have been employed to investigate the binding interaction between Bovine Serum Albumin (BSA) and the titled complex. The complex induced significant fluorescence quenching of BSA, indicating a strong binding affinity for the protein. Static or ground state complex formation was envisaged as the primary quenching mechanism when the complex interacts with BSA. In addition, the Ag compound also offers photocatalytic properties by degrading the toxic organic methylene blue dye.

Aminoquinolines: Fluorescent sensors to DNA – A minor groove probe. Experimental and in silico studies

An aminoquinoline (AQ4) was developed and proven to be a new and efficient DNA minor groove fluorescent probe. The specificity for DNA minor groove was attested by comparing it with well-established DNA probes such as Hoechst stain, acridine orange, and ethidium bromide. AQ4 was similar to the Hoechst stain, a classic minor groove probe, and opposite to acridine orange and ethidium bromide, the typical intercalating probes. An advantage of AQ4 to the Hoechst stain was the higher fluorescent signal-to-noise ratio (+DNA/-DNA). The interaction with DNA leads to an exclusive fluorescent band centered at 590 nm. The red-shifted fluorescent band is associated with a new absorption band (490 nm), revealing a ground-state complex formation. The complexation was also evidenced by circular dichroism, anisotropy, and fluorescence lifetime. The complex AQ4-DNA was pH dependent, being favored in an acidic medium. This feature was related to the preferential interaction with a protonated form of AQ4, i.e., AQ4(H+), revealing the role of electrostatic forces, which was corroborated by the strong dependence on the ionic strength of the medium and, particularly, on magnesium ions. The complexes were studied by docking and molecular dynamics and confirmed the stability of AQ4(H+). Additionally, 500 ns simulations were performed by adding salts. The presence of the salts leads to the loss of the binding of AQ4(H+) after 52 ns (NaCl) and 142 ns (MgCl2). Experimental and in silico outcomes showed the advantages of the aminoquinoline over the commercial DNA minor groove stain, the Hoechst dye. Hence, we propose its further application in cell-based assays.

Multi-spectroscopic and molecular simulation methods of analysis to explore the mode of binding of Mebendazole drug with calf-thymus DNA

UV–vis, fluorescence, circular dichroism (CD) and 1H NMR spectroscopic techniques have been employed to explore the mode of binding of Mebendazole (MBZ) drug with calf thymus DNA (CT-DNA). UV–vis and fluorescence spectral studies suggested a complex formation between the drug and nucleic acid. The fluorescence of MBZ was found to enhance upon binding with CT-DNA through a ground state complex formation with Kb in the order of 104 M−1. The thermodynamic aspects indicated that the complex formation is a spontaneous process and an entropy-driven one. ΔH0 > 0 and ΔS0 > 0 revealed that hydrophobic interaction plays a dominant role in the stabilization of the complex. Competitive dye displacement assays with ethidium bromide (EB) and Hoechst 33258 dyes and viscosity measurements pointed out that MBZ binds with CT-DNA via intercalation mode, which is confirmed by CD and 1H NMR spectral studies as well as denaturation studies. Molecular docking analysis could not match well with the experimental results. However, molecular simulation studies and the resultant free energy surface (FES) analysis clearly showed that the benzimidazole ring of MBZ intercalated between the base pairs of the nucleic acid, which is in excellent agreement with the results of the various biophysical experiments.

Tryptanthrin-malononitrile adduct for highly efficient turn-off fluorescent sensing of aniline

The fluorescence quenching of 2-(8-chloro-12-oxo-12H-indolo[2,1-b]quinazolin-6-ylidene)-malononitrile (5a) by aniline was studied in detail. Time correlated single photon counting measurements (TCSPC) indicated that the quenching involved both static and dynamic mechanisms without ground state complex formation. The selectivity towards aniline sensing in presence of other amines/aromatics and the anti-interference studies together with the low LOD value indicates the potential of 5a as a molecular probe for aniline sensing which is unaffected by pH alteration as well.

Bioactives Promiscuity of Mucin: Insight from Multi-Spectroscopic, Thermodynamic, and Molecular Dynamic Simulation Analyses.

Mucosal drug delivery plays an increasing role in the clinical setting owing to mucin's advantageous biochemical and pharmacological properties. However, how this transport system recognizes different substrates remains unclear. In this study, we explore the mechanism of bioactive (quercetin and berberine) promiscuity of mucin using various spectroscopic techniques and molecular dynamics simulations. The UV-visible spectroscopy results and the decreased fluorescence intensity of mucin in the presence of the bioactive compounds via a static quenching mechanism confirmed ground-state complex formation between the bioactives and mucin. The binding constants (Kb) were evaluated at different temperatures to afford Kb values of ∼104 Lmol-1, demonstrating the moderate and reasonable affinity of the bioactives for mucin, yielding greater diffusion into the tissues. Thermodynamic analysis and molecular dynamics (MD) simulations demonstrate that mucin-bioactive complex formation occurs primarily because of electrostatic/ionic interactions, while hydrophobic interactions were also crucial in stabilizing the complex. Far-UV circular dichroism spectroscopy showed that bioactive binding induced secondary structural changes in mucin. Sitemap and MD simulation indicated the principal binding site of mucin for the bioactives. This study also provides insight into the bioactives promiscuity of mucin in the presence of a crowded environment, which is relevant to the biological activity of mucin in vivo. An in vitro drug release study revealed that crowding assisted drug release in an enhanced burst manner compared with that in a dilute buffer system. This work thus provides fresh insight into drug absorption and distribution in the native cellular environment and helps direct new drug design and use in pharmaceutical and pharmacological fields.