Binding Constants Research Articles

Study on the interaction mechanism of whey protein isolate with phosphatidylcholine: By multispectral methods and molecular docking.

The elucidation of the interaction mechanism between phospholipids and milk proteins within emulsions is pivotal for comprehending the properties of infant formula fat globules. In this study, multispectral methods and molecular docking were employed to explore the relationship between phosphatidylcholine (PC) and whey protein isolate (WPI). Observations indicate that the binding constant, alongside thermodynamic parameters, diminishes as temperature ascends, hinting at a predominantly static quenching mechanism. Predominantly, van der Waals forces and hydrogen bonds constitute the core interactions between WPI and PC. This assertion is further substantiated by Fourier transform infrared spectroscopy, which verifies PC's influence on WPI's secondary structure. A detailed assessment of thermodynamic parameters coupled with molecular docking reveals that PC predominantly adheres to specific sites within α-lactalbumin, β-lactoglobulin, and bovine serum albumin, propelled by a synergy of hydrophobic interactions, hydrogen bonding, and van der Waals forces, with binding energies noted at -5.59, -6.71, and -7.85kcal/mol, respectively. An increment in PC concentration is observed to amplify the emulsification properties of WPI whilst concurrently diminishing the zeta potential. This study establishes a theoretical foundation for applying the PC-WPI interaction mechanism in food.

Screening and analysis of the targeted compounds in Choerospondias axillaris extract by receptor chromatographic column with immobilized angiotensin II type 1 receptor.

As a result of the lack of modern techniques, the study of Tibetan medicine has been hindered in identifying bioactive compounds. Herein, we established a chromatographic approach using an immobilized angiotensin II type 1 receptor (AT1R) via a one-step method triggered by haloalkane dehalogenase. The bioactive compounds from Choerospondias axillaris (Guangzao) were screened and identified using the immobilized AT1R followed by MS. Frontal analysis (FA) and adsorption energy distribution (AED) were used to evaluate the association constants. Molecular docking was used to investigate the binding configurations, and the surface efficiency index, binding efficiency index, and ligand-lipophilicity efficiency (LLE) were calculated to assess the drug-like properties. The results identified naringenin, pinocembrin, and chrysin as the compounds that specifically bind to AT1R in Guangzao. FA and AED confirmed that there is only one type of binding site between these compounds and AT1R. The association constants were (2.40 ± 0.02) × 104 M-1 for naringenin (5.22 ± 0.26) × 104 M-1 for pinocembrin, and (4.27 ± 0.14) × 104 M-1 for chrysin, respectively. These compounds can bind with AT1R through the orthosteric binding pocket. Naringenin exhibited better LLE than pinocembrin and chrysin. These results confirmed the feasibility of using the immobilized AT1R column for screening and analyzing bioactive compounds in Tibetan medicines.

Sensing of Co2+ and Cu2+ Ions Using Dimethylamino-functionalized Poly(azomethine-1,3,4-oxadiazole)s.

The ability of OxT and OxFl azomethines to recognize metal ions in THF solutions was investigated using UV-vis absorption techniques. Various metal ions, including Cd2+, Hg2+, Co2+, Sn2+, Cu2+, Ni2+, Zn2+ and Ag+, were tested. The absorption spectra revealed two distinct π-π* transition bands in the 273-278nm and 330-346nm wavelength ranges. Additionally, OxFl displayed an absorption peak at 309nm, attributed to the fluorene group. Spectral titrations were used to study the fluorescence behavior in the presence of these metal ions. The results showed significant quenching with Co2+ and Cu2+ ions, while other metal ions had minimal effects on the fluorescence intensity. The quenching mechanism was further analyzed using the Stern-Volmer and Lehrer equations, and the binding constants ( ) were calculated using the Benesi-Hildebrand relations. The results confirm that Co2+ has a 1:2 stoichiometry and Cu2+ has a 1:1 stoichiometry, indicating the strong affinity of OxFl and OxT for these ions. The negative values of ΔG (Gibbs free energy) suggest that complex formation occurs spontaneously at room temperature.

Insights into the roles of heat‐stable protein derived from egg white in vitamin A stabilisation

SummaryVitamin A (VA) is a fat‐soluble compound that is essential for physiological functions including vision, fetal growth, immune response, cell differentiation and proliferation. However, its susceptibility to environmental conditions leading to poor stability limits its application in food. This study investigated the interaction between egg white protein (EWP) and VA by spectroscopy and molecular docking. The results indicated one EWP could bind 16.00 ± 0.89 VA molecules and the binding constant is (2.59 ± 0.71) × 105 m−1. What's more, there was a fluorescence resonance energy transfer between EWP and VA, and the Förster radius is 5.28 nm. In addition, VA enhanced the hydrophobic interactions with the EWP, resulting in protein aggregation, larger average particle size and more uniform particle size distribution. Finally, the combination of VA with EWP could significantly improve the photothermal stability and storage stability of VA. These studies indicate that EWP nanocomplexes can be used as ideal delivery carriers for bioactive substances.

Cation-Binding of Glutamate in Aqueous Solution.

Interactions of the cations Li+, Na+, Mg2+, and Ca2+ with L-glutamate (Glu-) in aqueous solution were studied at room temperature with dielectric relaxation spectroscopy in the gigahertz region. Spectra of ∼0.4 M NaGlu with added LiCl, NaCl, MgCl2, or CaCl2 (c(MCln) ≤ 1.5 M) were evaluated and experiments supplemented by density functional theory and 3D reference interaction site model (3D-RISM) calculations. In addition to the modes found for aqueous NaGlu, namely, the reorientation of free Glu- ions (peaking at ∼1.6 GHz), of moderately retarded H2O molecules hydrating the carboxylate moieties of Glu- (∼8.4 GHz), of the cooperative resettling of the H-bond network of bulk water (∼20 GHz), and its preceding fast H-bond flip (∼400 GHz), an additional low-frequency relaxation at ∼0.4 GHz was detected upon the addition of the four salts. In the case of NaGlu + MgCl2(aq) and NaGlu + CaCl2(aq), this mode could be unequivocally assigned to an ion pair formed by the cation and the side-chain carboxylate moiety of Glu-. For NaGlu + LiCl(aq), either this species or a backbone-[Li+-H2O-Cl--Glu-] triple ion is formed. Binding constants increase in the order Li+<Mg2+<Ca2+. For NaGlu + NaCl(aq), an assignment of the ∼0.4 GHz mode to ion pairs or triples was not plausible. Accordingly, its origin remains speculative here.

Antibacterial and cytotoxicity studies of pyrrolo-based organic scaffolds and their binding interaction with bovine serum albumin.

Two pyrrolo-based compounds, 1H-pyrrolo[3,2-b]pyridine-3-carboxylic acid (L1) and 1H-pyrrolo[3,2-c]pyridine-4-carboxylic acid (L2), were employed for the detection of bovine serum albumin (BSA) by UV-Vis and fluorescence spectroscopic methods in phosphate buffer solution (pH = 7). In the presence of L1 and L2, the fluorescence emission of BSA at 340 nm was quenched and concomitantly a red-shifted emission band appeared at 420 nm (L1)/450 nm (L2). The fluorescence spectral changes indicate the protein-ligand complex formation between BSA and L1/L2. An isothermal titration calorimetry (ITC) experiment was conducted to determine the binding ability between BSA and L1/L2. The binding constants are found to be 4.45 ± 0.22 × 104 M-1 for L1 and 2.29 ± 0.11 × 104 M-1 for L2, respectively. The thermodynamic parameters were calculated from ITC measurements (i.e. ∆rH = -40 ± 2 kcal/mol, ∆rG = -4.57 ± 0.22 kcal/mol and -T∆rS = 35.4 ± 1.77 kcal/mol), which indicated that the protein-ligand complex formation between L1/L2 with BSA is mainly due to the electrostatic interactions. The protein-ligand interactions were studied by performing molecular docking. Further, the antibacterial assay of L1 and L2 was conducted against gram-positive and gram-negative bacterial strains in an effort to address the difficulties caused by the co-occurrence of antimicrobial and multidrug-resistant bacteria. E. coli and S. aureus were significantly inhibited by L1 and L2. The L1 exhibits 13, 12 and 15 mm, whereas L2 exhibits a 2, 3 and 5 mm zone of inhibition against S. aureus, S. pyogenesand E. coli, respectively. In silico molecular docking of L1 and L2 was performed with bacterial DNA gyrase to establish the intermolecular interactions. Finally, the in vitro cytotoxicity activities of the ligands L1 and L2 have been carried out using drosophila.

Physicochemical investigations of nootropic drug piracetam for enhanced solubilization as nano drug carrier under the influence of single and mixed micellar formulations: An optimized approach towards drug delivery

Nonionic surfactants have drawn tremendous attention for micellar solubilization, sustained release of the drug, encapsulation of pharmaceutically active ingredients, and permeabilization due to their distinct physicochemical characteristics. Concise solubility investigations are required for the appropriate selection of nonionic surfactant that is to be used for a formulation. In the present research, a cluster of micelles was developed that relies on trapping and stabilizing piracetam by balancing the hydrophilic and hydrophobic forces of nonionic surfactants. Tween 80 and Triton-X 100 and a mixture of these surfactants were used to clarify the drug-surfactant interaction in an aqueous and micellar medium. The interaction was investigated in premicellar, micellar, and post-micellar regions by using UV/Visible spectroscopy. Spectroscopic parameters were calculated to determine the degree of solubilization in terms of the partition coefficient (Kx), binding constant (Kb), and their respective energies in terms of Gibbs free energy of partition (ΔGp) and Gibbs free energy of binding (ΔGb) for piracetam. The solubilization of piracetam is enhanced by mixing an adequate amount of both nonionic surfactants. The obtained results demonstrated that solubilization is spontaneous and entropically favorable and the cluster of micelles in both single and mixed micellar mediums are stable due to the presence of a much more hydrophobic and hydrophilic culture which provides a synergistic link between the two surfactants.

A Comparative Analysis of the Interaction between Donepezil and Albumin with and Without a ZnO/Chitosan Quantum Dot Nanocomposite

AbstractIn this study, a nanocomposite of zinc oxide (ZnO) nanoparticles and chitosan‐based carbon quantum dots (ZnO/chQDs) in the presence of bovine serum albumin (BSA) as a promising drug carrier candidate was synthesized and characterized. For this purpose, chitosan and citric acid were used for the synthesis of chQDs and donepezil (DNP) was selected as a model drug. The BSA binding properties of DNP were analyzed by FT‐IR and UV‐Vis techniques, electrochemical methods and molecular docking in the absence and presence of ZnO/chQDs. The thermodynamic parameters and binding constants of DNP with BSA were also evaluated by these methods. The changes in the structural properties of BSA in the presence of DNP, ZnO/chQDs and ZnO/chQDs‐DNP were monitored by ATR‐FTIR spectroscopy. Cyclic and differential pulse voltammetric techniques and electrochemical impedance spectroscopy were applied to investigate the interactions, using methylene blue in electrolyte solution as redox probe, and its redox behaviour was observed to explore the interactions. Molecular docking was carried out on the interaction of DNP with BSA in the absence and presence of the synthesized ZnO/chQDs, and the results were compared with those of the experimental observations. The experimental results were confirmed by molecular docking studies.

Bifunctional fluorescent probe for fluoride and copper(Ⅱ) based on perylene diimide derivative and its application in cell imaging

A bifunctional fluorescent probe P1 based on perylene diimide derivative (PDI) was developed, demonstrating high sensitivity and selectivity for the rapid detection of fluoride (F-) and copper (Cu2+). The fluorescence of P1 was quenched upon interaction with F- and enhanced upon interaction with Cu2+. The concentration ranges for fluorescent detection of F- and Cu2+ are 0 ∼ 4 × 10-5 M and 0 ∼ 2.4 × 10-5 M, respectively. The stoichiometry of the complex formed between Cu2+ and P1 or F− and P1 was 1:1. The probe displays detection limits of 0.16 and 0.21 μM and binding constants (Ksv) of 3.92 × 104 and 1.72 × 104 M−1 for the detection of F- and Cu2+, respectively. The sensing mechanism and binding mode of P1 with F- and Cu2+ were investigated. The fluorescence quenching/enhancement of P1 was controlled by a photoinduced electron-transfer (PET) process. Furthermore, the ability of the probe to detect intracellular F- and Cu2+ was assessed using cell imaging techniques.

Synthesis and characterization of magnetic molecularly imprinted polymers for the rapid and selective determination of clofazimine in blood plasma samples

Clofazimine (CLF) is a riminophenazine derivative and a new therapeutic option with high efficacy for patients with rifampicin-resistant tuberculosis (TB). The blood levels of CLF are low and suboptimal, so therapeutic drug monitoring is required. Prior to this study, there were no molecular imprinting–based solid phase extraction (SPE) sorbents that could be used to determine the blood CLF levels. Hence, we prepared a magnetic molecularly imprinted polymer (MMIPs) to capture CLF. We employed computational selection of a functional monomer and crosslinker and confirmed these selections based on the association constant (Ka) and a Job plot. We synthesised MMIPs with two surface modifiers and characterized the polymers. Our computational analysis based on the bond energy revealed that methyl methacrylate (MMA) was the most suitable functional monomer at a CLF-to-MMA molar ratio of 1:4. Based on the bond energy, the most suitable crosslinker was trimethylolpropane trimethacrylate (TRIM) at a CLF-to-TRIM molar ratio of 1:1. We determined the Ka of MMA and TRIM in different solvents. Isopropanol produced the highest Ka. The Job plot showed that a template-to-MMA-to-TRIM molar ratio of 1:4:20 was optimal to synthesize imprinted polymer in isopropanol. We prepared MMIPs using two different modifiers, namely aminopropyltrimethoxysilane (APTES) and oleic acid (OA), using the ratio determined from the Job plot. Physical characteristic tests carried out using FT-IR, SEM-EDS, PSA, BET and VSM, showed that the synthesis was success with a spherical and uniform agglomeration of particles, also a flat surface with many holes with a particle size of MMIP-APTES and MMIP-OA respectively 0.14 μm and 0.28 μm, showed a surface area for MMIP-APTES is 2874.51 m2/g and MMIP-OA 2913.07 m2/g, exhibiting superparamagnetic properties with a saturation magnetization value of MMIP-APTES 21.1 emu/g−1 and MMIP-OA 49.9 emu/g−1. Adsorption capacity result showed that MMIP-OA fits well with the Langmuir model, while MMIP-APTES fits better with the Freundlich. Application of MMIP-SPE (Magnetic Molecular Imprinted Polymer-Solid Phase Extraction) APTES resulted 92.3 ± 6.1 % and MMIP-SPE-OA 51.5 ± 8.1 % for recovering CLF in blood. The result of selectivity test also showed that MMIP-SPE-APTES is better than MMIP-SPE-OA and selectively recover CLF from human blood plasma existed together with other TB-Drugs. The study result shows that MMIPs with APTES modification can be used for CLF determination in human blood plasma.

Ultrasensitive detection of trace Hg(Ⅱ) in acidic conditions using DMABR loaded on sepiolite: Function, application and mechanism studies

Fast and real-time detection of trace Hg(Ⅱ) by fluorescent probes under acidic conditions is urgently required due to the high toxicity and accessibility to creatures and human being. However, fluorescent probes for Hg(Ⅱ) detection in environmental samples are rarely reported due to the protonation potential of acidic mercury sources. In this study, the SD probe was developed by 5-(p-dimethylaminobenzylidene) rhodanine (DMABR) loaded on sepiolite by hydrothermal treatment, and showed excellent Hg(Ⅱ) detection performances for mercury sources at pH 4–10 due to buffering ability of the hyperconjugated lactam rings. Sepiolite functioned as the support skeleton to decrease intermolecular transition, and thus increased the sensitivity. At pH 4, the SD probe showed high selectivity and sensitivity for Hg(Ⅱ) among various species, with low LOD and binding constant of 4.78 × 10−9 M and 1.34 × 106 M−1, respectively. Through DFT calculations, MAS 1H NMR and 2D-COS analysis, the detection mechanism was demonstrated as SN1 substitution of the spontaneous leaving H on amino groups in the transient state during tautomeric equilibrium, rather than the expected high-affinity sulphydryl. Additionally, the SD probe exhibited promising potential in quantifying water-soluble and bioavailable Hg(Ⅱ) in acidic polluted soil and water samples. Moreover, real-time detection was realized by paper-based strips.

Efficacy of Click derived 1,2,3-Bistriazole on selective recognition of Co(II) and its application in seed germination

The present investigation supports the synthesis of Bis-Triazole allied S-heterocyclic based Schiff base via click chemistry and simple condensation approach. The molecular docking was performed on both the compounds which interprets that after the addition of Schiff base to Bis-Triazole moiety it showed better binding affinity for cytochrome p450 oxidase. Further the effect of compound-4 was seen on the seedling growth of Zea mays and Medicago sativa. When applied to Zea mays, compound-4 demonstrated its best benefits at a concentration of 0.5 mg L−1, whereas 10 mg L−1 of Medicago sativa displayed promising results. In addition, UV–Vis. Absorbance studies revealed that compound-4 selectively detects Co(II) in presence of several other metal ions, with good value of limit of detection and association constant.

Interaction of anionic dye ethyl orange and cationic CnTAC surfactants: A multi technique investigation

This research presents the application of electrical conductivity measurements to ascertain the critical micelle concentration (CMC) values for N-alkyltrimethylammonium chloride surfactants (CnTAC; with alkyl chain lengths of n = 12, 14, 16, and 18). Complementary spectrophotometric analysis was conducted to probe the interactions between CnTAC series and Ethyl Orange (ETO), an anionic dye. Applying the Benesi-Hildebrand and Scott equations, we evaluated the binding constant (Kb) of the cationic micelles’ interaction with ETO, which in turn facilitated calculations of Gibb’s free energy (ΔG°) changes. These calculations provided insight into the binding affinity of ETO to the micelles. Our findings suggest that the interaction between ETO and CnTAC is contingent on the surfactant concentration, with higher concentrations leading to a disassociation of the ETO-CnTAC complex and a reduction in ETO adsorption. Notably, the alkyl chain length within CnTAC molecules critically affects various properties, including ΔG°, CMC, and other thermodynamic parameters that determine the surfactant’s energetic behavior. The study underscores the importance of the alkyl chain length in dictating the interaction dynamics and properties of CnTAC surfactants. A trend was observed where longer alkyl chains lead to increased Kb values and reductions in both CMC and ΔG°, enhancing dye solubilization and interaction spontaneity. The affinity sequence of ETO to the micelles, influenced by alkyl chain length, was found to be C12TAC < C14TAC < C16TAC < C18TAC.

Pf bacteriophages hinder sputum antibiotic diffusion via electrostatic binding.

Despite great progress in the field, chronic Pseudomonas aeruginosa (Pa) infections remain a major cause of mortality in patients with cystic fibrosis (pwCF), necessitating treatment with antibiotics. Pf is a filamentous bacteriophage produced by Pa and acts as a structural element in Pa biofilms. Pf presence has been associated with antibiotic resistance and poor outcomes in pwCF, although the underlying mechanisms are unclear. We have investigated how Pf and sputum biopolymers impede antibiotic diffusion using pwCF sputum and fluorescent recovery after photobleaching. We demonstrate that tobramycin interacts with Pf and sputum polymers through electrostatic interactions. We also developed a set of mathematical models to analyze the complex observations. Our analysis suggests that Pf in sputum reduces the diffusion of charged antibiotics due to a greater binding constant associated with organized liquid crystalline structures formed between Pf and sputum polymers. This study provides insights into antibiotic tolerance mechanisms in chronic Pa infections and may offer potential strategies for novel therapeutic approaches.

Azine Based Oligoesteric Chemosensors for Cu2+ Ion Detection: Synthesis, Structural Characterization, and Theoretical Investigations.

Synthesized monomer and its three oligoesters were characterized by techniques such as 1H, 13C{1H}, IR, UV, GPC and applied to chemosensor applications. A series of metal ions was studied with fluorophores to evaluate the sensitivity towards Cu2+ ion. The fluorophores results exhibit the selective and sensitive "Turn off" fluorescence response with Cu2+ ion in DMF/H2O (1:1, pH: 7.4, fluorophore: 5µM) solution. Binding stoichiometry and binding constant of fluorophores were calculated using Stern-Volmer equation and Benesi-Hildebrand plots, respectively. Structure of fluorophores were studied using DFT, B3LYP/6-311 + + G(d,p) level basis set. Quenching mechanisms and electrical properties of fluorophores were explained with theoretical outcomes. Iodine doped and undoped oligoesters electrical conductivity were studied in solid-state and the conductivity was gradually increased with increase the contact time of iodine with oligoesters. At different frequencies and temperatures, the dielectric measurement was calculated using the two-probe method. Among all oligoesters, DMDAP exhibited high electrical conductivity and DMDMP has a higher dielectric constant value than other oligoesters.

Probing noncovalent binding, spectroscopic characteristics and antiproliferative behavior of inclusion complex between quinoline and para-sulfonatothiacalix[4]arene

The inclusion complex between bowl-shaped para-sulfonatothiacalix[4]arene (TSCX4) macrocycle and quinoline has been studied with a unison of UV–visible, infra-red, flourescence emission and 1H nuclear magnetic resonance (NMR) and 2D nuclear overhauser effect spectroscopy (NOESY), high resolution mass spectrometry (HRMS) experiments. Both 1H NMR titration and HRMS experiments point to 1:1 stoichiometry for the water soluble Q⊂TSCX4 complex. The electronic structure of the inclusion complex obtained from density functional theory (DFT) showed a partial encapsulation of quinoline guest, which is held within the host cavity by C–H---π, π---π and hydrogen bonding interactions. The fluorescence emission spectra upon complexation display marginal blue shift of the 411 nm band in TSCX4. Moreover, the binding constant (7.1 × 103 M−1) determined from fluoresence emission experiments underline the effective host–guest binding in the complex, which was corroborated through frequency up-shift (‘blue shift’) of characteristic Ar-OH (3433 cm−1) and SO3- vibrations (1141 cm−1 and 1037 cm−1) in the measured infrared spectra of TSCX4. The antiproliferative activitities of the Q⊂TSCX4 complex against HeLA, MDA-MB-231and N2a cells are presented. The Q⊂TSCX4 complex has been shown to be efficient against N2a (neuroblastoma) cell line.

Exploring the therapeutic potential of rutin through investigating its inhibitory mechanism on lactate dehydrogenase: Multi-spectral methods and computer simulation

Lactate dehydrogenase (LDH), a crucial enzyme in anaerobic glycolysis, plays a pivotal role in the energy metabolism of tumor cells, positioning it as a promising target for tumor treatment. Rutin, a plant-based flavonoid, offers benefits like antioxidant, antiapoptotic, and antineoplastic effects. This study employed diverse experiments to investigate the inhibitory mechanism of rutin on LDH through a binding perspective. The outcomes revealed that rutin underwent spontaneous binding within the coenzyme binding site of LDH, leading to the formation of a stable binary complex driven by hydrophobic forces, with hydrogen bonds also contributing significantly to sustaining the stability of the LDH-rutin complex. The binding constant (Ka) for the LDH-rutin system was 2.692 ± 0.015 × 104 M−1 at 298 K. Furthermore, rutin induced the alterations in the secondary structure conformation of LDH, characterized by a decrease in α-helix and an increase in antiparallel and parallel β-sheet, and β-turn. Rutin augmented the stability of coenzyme binding to LDH, which could potentially hinder the conversion process among coenzymes. Specifically, Arg98 in the active site loop of LDH provided essential binding energy contribution in the binding process. These outcomes might explain the dose-dependent inhibition of the catalytic activity of LDH by rutin. Interestingly, both the food additives ascorbic acid and tetrahydrocurcumin could reduce the binding stability of LDH and rutin. Meanwhile, these food additives did not produce positive synergism or antagonism on the rutin binding to LDH. Overall, this research could offer a unique insight into the therapeutic potential and medicinal worth of rutin.

Theoretical Investigation and Design of Bioactive Quinoline Derivatives as Inhibitors of DNA Gyrase of Salmonella typhi

The ever-increasing rate of resistance to existing antibiotics by Salmonella typhi has made the search for novel drug candidates a necessity. In this study, Molecular docking technique was used to screen 18 bioactive quinoline derivatives against DNA gyrase of Salmonella typhi using PyRx graphical user interface of AutoDock Vina software. Ligand with the best binding affinity against the target macromolecule was used as prototype to design novel analogues with enhanced potencies. With the aid of Swiss ADME online server and Osiris DataWarrior v5.5.0 programme, the absorption, distribution, metabolism, excretion and toxicity (ADMET) profiles of the ligands were evaluated and their electronic properties were computed using density functional theory (DFT) method of Spartan 14.0 software. Ligand 3 (L3) with the best binding affinity (TG) value of −10.5 kcal/mol was chosen as a prototype to design La and Lb with TG value of −10.7 kcal/mol and −10.8 kcal/mol; binding constant (ka) of 7.04 × 107 and 8.35 × 107 ; and dissociation constant (kd) of 1.42 x 10−8 and 1.2 × 10−8, respectively. When compared with ciprofloxacin (TG = −7.7 kcal/mol), the ligands could be more potent. Likewise, the ligands were found to possess excellent oral bioavailability and pharmacokinetic profiles. Furthermore, DFT calculations on La and Lb revealed that they possess highest occupied molecular orbital-lowest unoccupied molecular orbital (HOMO-LUMO) energy gap of 3.46 eV and 3.45 eV; and global electrophilicity index of 3.83 eV and 3.96 eV, respectively. The designed ligands tend to be consistent with all the validation protocols deployed in this study and as such could be recommended as novel drug candidates for treatment of Salmonella typhi induced salmonellosis.

Characterization of the structural and molecular interactions of Ferulic acid ethyl ester with human serum albumin and Lysozyme through multi-methods

Ferulic acid ethyl ester (FAEE) is an essential raw material for the formulation of drugs for cardiovascular and cerebrovascular diseases and leukopenia. It is also used as a fixed aroma agent for food production due to its high pharmacological activity. In this study, the interaction of FAEE with Human serum albumin (HSA) and Lysozyme (LZM) was characterized by multi-spectrum and molecular dynamics simulations at four different temperatures. Additionally, the quenching mechanism of FAEE-HSA and FAEE-LZM were explored. Meanwhile, the binding constants, binding sites, thermodynamic parameters, molecular dynamics, molecular docking binding energy, and the influence of metal ions in the system were evaluated. The results of Synchronous fluorescence spectroscopy, UV–vis spectroscopy, CD, three-dimensional fluorescence spectrum, and resonance light scattering showed that the microenvironment of HSA and LZM and the protein conformation changed in the presence of FAEE. Furthermore, the effects of some common metal ions on the binding constants of FAEE-HSA and FAEE-LZM were investigated. Overall, the experimental results provide a theoretical basis for promoting the application of FAEE in the cosmetics, food, and pharmaceutical industries and significant guidance for food safety, drug design, and development.

Novel azo- and bisazo-5-pyrazolone dyes and their application as a colorimetric chemosensor for naked eye recognition of Cu2+

In this study, novel azo- and bisazo-5-pyrazolones (1/2a, b, and 1/2c, d, respectively) were synthesized. The structures of the new compounds were characterized using FTIR, UV–Vis., 1H NMR, 13C NMR-APT, and HRMS spectroscopic methods. 1H-NMR study revealed that the compounds are in hydrazone- form in solution. Among fourteen metal nitrate salts, the azo-5-pyrazolones showed a colorimetric response only to the Cu2+ ion, whereas the new bisazo-5-pyrazolones did not cause a specific color change to only one cation. The produced ligand changed from orangey-yellow to very light yellow, making it possible to identify Cu2+ without the need for spectroscopic equipment. Compound 1b [4-((2,4-dimethylphenyl)diazenyl)-2-(naphthalene-1-yl)-5-phenyl-2,4-dihydro-3H-pyrazole-3-one)] was taken as a representative example of the new azo-5-pyrazolones for the chemosensor research. The Cu(1b)2 complex was also synthesized and characterized. The binding ratio between the 1b sensor and Cu2+ was found to be 2:1 (ligand:metal) from the structural characterization of Cu(1b)2 and using Job's plot method. The pH study showed that even if the pH changes, the Cu2+ ion can still bind to the 1b receptor. In the reversibility experiment, when EDTA was added to the (1b+Cu2+) solution, the spectrum returned to the 1b spectrum. The interference study showed the selectivity of 1b with Cu2+ even in the presence of other cations. A study of the detection limit (LOD) revealed considerable sensitivity towards Cu2+metal cation using absorption titration method and LOD value was found to be 4.31 μM. The association constant (Ka) of (1b+Cu2+) was determined to be 0.79×105M−1 using the Benesi-Hildebrand plot.