Binding Constants Research Articles

Strong electrostatic attraction drives milk heteroprotein complex coacervation

Coacervates of oppositely charged milk proteins are used in functional food development, mainly to encapsulate bioactives. To uncover the driving forces behind coacervates formation, we study the association of lactoferrin and β−lactoglobulin at amino-acid level detail, using molecular simulations. Our findings show that inter-protein electrostatic interactions dominate and are, surprisingly, equally divided between an isotropic part, due to monopole-monopole attraction of the oppositely charged proteins, and an anisotropic part due to uneven surface charge distributions. In good agreement with recent experimental association constants, the calculated protein-protein interaction free energy is strongly dependent on pH and salt concentration. In addition to thermodynamics, we also investigate amino acid contacts in microstates of trimeric and pentameric protein complexes, and identify interaction hot-spots that drive heteroprotein complex coacervation process.

Efficient encapsulation of insulin by a giant macrocycle as a powerful approach to the inhibition of its fibrillation.

Diabetes is a lifelong metabolic disease that requires frequent subcutaneous injections of insulin. However, free insulin is prone to forming immunogenic fibrillar aggregates under physiologic conditions, which limits its biomedical applications. Here, an approach to inhibiting insulin fibrils was developed through entire encapsulation by a giant macrocyclic inhibitor agent. Negatively charged water-soluble Pentaphen[3]arene sulfate (PP[3]AS), bearing 15 benzenes on its skeleton, was designed and synthesized. In vitro and in vivo safety tests preliminarily demonstrated that PP[3]AS had excellent biocompatibility. PP[3]AS could not only effectively inhibit the formation of amyloid, but also disaggregate intractable mature insulin fibrils. This macrocyclic inhibitor exhibited effective host-guest complexation toward insulin at the C-terminal 11-mer peptide sequence of the B chain with association constants of (5.69 ± 0.50) × 106 M-1. Such complexation behavior is distinctive to traditional macrocycles, which can only recognize amino acid residues from the side due to their limited cavity sizes. Control experiments also proved that smaller cucurbit[7]uril and carboxylatopillar[5]arene could not prevent insulin from fibrillation under the same test conditions. Notably, co-administration with equimolar PP[3]AS maintained normoglycemia for at least 300 min in streptozotocin-induced diabetic model mice, whereas mice that received free insulin became hyperglycemic again within ∼150 min.

Trace level detection of Pb2+ ion using organic ligand as fluorescent-on probes in aqueous media.

In this study, an optical sensor, JA/(2,6-di((E)-benzylidene)cyclohexan-1-one), was synthesized and characterized using 1H NMR and FT-IR spectroscopy. The sensor exhibited high efficiency and selectivity in detecting Pb2+ ions, even in the presence of potential interfering ions such as Mn2+, Cu2+, Co2+, Cr3+, Ni2+, Ce3+, Hg2+, and Cd2+ in aqueous solutions. The interaction of JA with Pb2+ resulted in a significant enhancement of fluorescence intensity, suggesting the formation of a stable complex. A 2:1 binding ratio between JA and Pb2+ was confirmed through fluorometric analysis, absorption spectra, and theoretical calculations (DFT). The association constant for the complex was calculated to be 3×106M-2. The sensor demonstrated high sensitivity towards Pb2+ with a detection limit of 5×10-7M. Additionally, JA was successfully reused by applying EDTA to release Pb2+ from the sensor. Real sample analysis under optimized conditions of pH, time, and concentration of JA and Pb2+ further validated the practical applicability of the sensor.

The impact of encapsulation in cyclodextrin nanocavities on the participation of hydrogen bond assisted intramolecular charge transfer in fluorescence emission

This study investigates how incorporation of D-π-A derivatives in various cyclodextrin structures affects the identification of excited-state emission characteristics, focusing on the contribution of intramolecular charge transfer and hydrogen bond-assisted intramolecular charge transfer emissive states. In this context, the photophysical properties of 4-(5-(4-methoxyphenyl)thiophen-2-yl)benzamidine (I) and 2-fluoro-4-(5-(4-methoxyphenyl)thiophen-2-yl)benzamidine (II) in neutral aqueous solution and upon inclusion in various cyclodextrin derivatives were investigated by steady state and time-resolved measurements. Despite the very limited changes in the absorption spectra of the guest molecules upon addition of CDs, significantly large changes were observed in their steady-state fluorescence spectroscopy, both in the quantum yield of the fluorescence emission and their fluorescence lifetime results. Fluorescence decay profiles of (I) and (II) exhibited good fits with biexponential decay functions both in the presence and absence of the investigated CDs, with their respective contributions significantly dependent on the concentration of added cyclodextrin. The association constants derived from fluorescence decay measurements closely matched those obtained from steady-state fluorescence measurements. Inclusion of I and II in α-CD, β-CD, Mβ-CD, or HPβ-CD was confirmed using 1H NMR measurements, with notable 2D NOESY effects observed specifically for II..HPβ-CD complexes.

Smartphone-assisted colorimetric detection of nickel(II) ions using a novel benzothiazole-quinoline dyad in semi-aqueous media.

In this study, we present three different approaches for the colorimetric detection of Ni2+ ions using a specifically designed benzothiazole-quinoline dyad (L) synthesized via the Knoevenagel condensation reaction in high yield. The unique properties of L enable a rapid and selective response to Ni2+ ions, making it an ideal probe for practical applications. The probe L shows a pale yellow color under normal conditions. Upon interaction with Ni2+ ions, L undergoes a significant color change from pale yellow to bright orange, allowing for visual detection in semi-aqueous media. This rapid colorimetric response enables real-time monitoring of Ni2+ concentrations. The absorption maximum of L undergoes a bathochromic shift in the presence of Ni2+ ions due to ligand-to-metal charge transfer (LMCT). The probe L could form a 2 : 1 [L : Ni2+] stoichiometric complex, confirmed through Job's plot and ESI mass analysis with an estimated association constant of 2.61 × 106 M-2. The probe L could detect Ni2+ concentration down to 61 nM, 106 nM, and 129 nM via a UV-Vis spectrophotometer, smartphone-assisted RGB method, and test paper strip analysis. The binding mechanism of probe L with metal ions was studied using 1H NMR, ESI mass spectrometry, and DFT calculations. The zeta potential analysis showed a potential of -28.38 mV for the free ligand and +12.09 mV upon complexation with Ni2+. More importantly, the potential application of probe L includes the quantification of Ni2+ ions in various water samples through all three sensing approaches.

A New Empirical Equation to Take Into Account the Influence of Ionic Strength on Electrophoretic Mobility and Determination of Binding Constants of Ester Betulin Derivatives With Sulfated β‐Cyclodextrin by Affinity Capillary Electrophoresis

ABSTRACTAn empirical equation relating electrophoretic mobility and ionic strength was proposed. The equation includes a number of parameters that are found using the mobilities of reference ions: two coefficients in the numerator describing the linear relationship of the multiplier in front of the square root of the ionic strength with the product of the ion mobility in the background electrolyte (BGE) without additives by the modulus of the charge number, raised to a certain power, and also the multiplier in the denominator before the square root of the ionic strength. The proposed equation was tested using the mobilities measured in BGEs with the addition of sodium chloride to adjust ionic strength and sulfated β‐cyclodextrin (S‐β‐CD) for 11 anions with charge numbers from −1 to −4. Measuring anion electrophoretic mobility over a wide range of values, from −17 to −76 × 10−9 m2 V−1 s−1, was achieved through a combination of conventional separation and separation in a thermostatically controlled part of a capillary. The equation describes experimental data much more accurately (the discrepancy is no more than 1.1%) compared to the previously used simple empirical equation. For the S‐β‐CD complexes of betulin derivatives, the apparent binding constants determined are equal to 40–60 M−1.

Thermosensitive Molecular Brushes With Alternating Polyoxazoline Side Chains: Synthesis, Characterization, and Solubilization Properties

ABSTRACTUsing the “grafting through” approach, alternating polymer brushes with different lengths of the backbone and side chains are synthesized. Thermosensitive poly(2‐ethyl‐2‐oxazoline) and poly(2‐isopropyl‐2‐oxazoline) with styrene and maleimide moieties are used as the macromonomers. The prepared polymer brushes are characterized by molar masses in the range of 19,000–52,000 g·mol−1 and have a low dispersity Ð = 1.6–1.9. The number of side chains is from 10 to 20. The LCST behavior of alternating brushes in aqueous solutions is studied by light scattering and turbidimetry. Phase separation temperatures of aqueous solutions of alternating polymer brushes are varied from 37°C to 48°C depending on the length and number of the side chains, as well as on the polymer molar mass. The critical micelle concentrations depend on molar mass and the side chain length, changing from 1.12 × 10−5 to 9.40 × 10−4 mol·L−1, as established by the method of solubilization of a hydrophobic dye. Using the Benesi–Hildebrand method, the binding constants for curcumin and polymer brush samples are determined; their values range from 360 to 63,400 L·mol−1. It is shown that curcumin is effectively bound by polymer brush molecules in the aqueous solutions, which ensures the solubilization of hydrophobic curcumin in water.

Study of Newly Synthesized Pyridinium-based Cationic Surfactants for Drug Interaction and Antibacterial Activity

Two pyridinium-based new cationic surfactants have been synthesized by the reaction of 2-methylpyridine and 3-methylpyridine with an alkyl halide (1-bromoctadecane) using dry toluene as a solvent to get the compounds, N-(n-octadecyl)-2-methylpyridinium bromide (A1) and N-(n-octadecyl)-3-methylpyridinium bromide (A2), respectively. The synthesized samples were characterized by using various spectroscopic techniques. The synthesized compounds showed a critical micelle concentration in a very low-value range (0.111 mM to 0.125 mM), proving the synthesized compounds' best surface-acting ability. Both compounds exhibited limited antibacterial activity across various bacterial strains, with inhibition zones ranging from 3 to 7 mm. The change in Gibb’s free energy (ΔG) was also calculated from their binding constant (Kb) for samples A1 (-10.0 kJ/mol) and A2 (-19.37 kJ/mol). The samples demonstrated spontaneous interactions with the drug molecules, which proved the efficient bioavailability of the drug due to the best incorporation of drug molecules with the aggregated monomers of surfactant molecules.

Divalent Organo‐Bimetallic Chelates of Poly‐Dentate O,N,O‐dihydrazone Ligand as Effective Agents for Antitumor and Antimicrobial Assays, Interacting Modes With DNA

ABSTRACTSubstituted hydrazones and dihydrazones, as polydenatate ligand, reported high coordination chemical behavior towards numerous transition metals of different oxidation states for alternated applicable interest. Therefore, with a facile condensed reaction of the salicylaldehyde with tartric dihydrazide, a chelated tartrato‐dihydrazone ligand (H2Ltz) was formed. The coordinated features of H2Ltz versus two divalent metal ions of Cu (II) and Ni (II) ions were assumed to form two new bimetallic‐organic framework complexes, assigning triagonal bipyramidal and tetrahedral geometries (CuLtz and NiLtz, respectively). Their structural elucidating was determined within the analytical tools spectroscopically. The effectiveness of the growth inhibition for H2Ltz, CuLtz, and NiLtz against six named bacterial and fungal series, and three human cancer cell lines were examined discovering the reactive role of two central M (II) ions in CuLtz and NiLtz, respectively. The binding character of H2Ltz, CuLtz, and NiLtz, with calf thymus DNA, that is, DNA, was estimated based on the variation in viscometric/spectrophotometric features. The two bimetallic‐chelates represented more distinguished inhibitive attitudes than the regarded one of H2Ltz assigning to the inhibitive zones (mm) and the half‐inhibited concentration (IC50, μM) of growth inhibition of the studied microbes and human tumor cells, respectively. The examination of the binding action of H2Ltz, CuLtz, and CuLtz with DNA was approved according to the enhanced viscosity and the electronic spectral changes. Also, binding constants (14.09, 15.09, and 16.12 107 mol−1 dm3), Gibb's free energy (−42.06, −45.23, and −46.41 kJ mol−1), and the chromism (mainly hypo modes) are assigned to estimate the binding modes. Rewardingly, the bimetallic‐chelates MLtz displayed modified binding action more than that of H2Ltz against DNA regarding their hydrophobicity/lipophilicity.

Diazocines as Guests of Cucurbituril Macrocycles: Light-Responsive Binding and Supramolecular Catalysis of Thermal Isomerization.

The photoswitching of supramolecular host-guest complexes is the basis of numerous molecularly controlled macroscopic functions, such as sol-gel transition, photopharmacology, the active transport of ions or molecules, light-powered molecular machines, and much more. The most commonly used systems employ photoactive azobenzene guests and synthetic host molecules, which bind as the stable E isomers and dissociate as the Z forms after exposure to UV light. We present a new, extraordinarily efficient cucurbit[7]uril (CB7)/diazocine host/guest complex with inverted stability that self-assembles under UV irradiation and dissociates in the dark. The association constants of the Z and E isomers in water differ by more than 104-fold. We also show that the thermally activated E → Z isomerization is significantly accelerated by CB7, which is a rare case of enzyme-like catalysis by transition state stabilization without product inhibition. In contrast to CB7, cucurbit[8]uril (CB8) binds both isomers with high affinity, showing good selectivity (∼1000-fold) toward the Z isomer. Notably, this isomer preferentially binds CB8 relative to CB7 by a factor greater than 1 × 106. We also use the system to introduce a supramolecular photoacid that builds on the increased basicity of a guest bound to CB7 and on the extremely high affinity of the E isomer, which is utilized to displace the acid from CB7, thereby switching the pH of the solution.

Uranyl Speciation in Carbonate-Rich Hydrothermal Solutions: A Molecular Dynamics Study.

In this study, we employed classical molecular dynamics (CMD) and first-principles molecular dynamics (FPMD) simulations to investigate the speciation of uranyl in carbonate-rich hydrothermal solutions. The association constants (log10KA) of uranyl carbonate complexes were derived from the potential of mean forces (PMFs) obtained from CMD simulations, and the acid constants (pKas) of uranyl aqua ions were calculated using the FPMD-based vertical energy gap method. The results showed that uranyl ions could form stable mono- and bi-carbonate complexes at elevated temperatures and that uranyl aqua ions strongly hydrolyzed in neutral solutions at temperatures exceeding 473 K. The speciation of uranyl in hydrothermal solutions was constructed based on the calculated thermodynamics data. It was found that uranyl carbonate complexes were predominant in aqueous solutions at temperatures below 373 K, and at higher temperatures, UO2(OH)2/UO2(OH)+ became the predominant species. These findings provide molecular-level insight into the speciation of uranyl in hydrothermal solutions and highlight the role of uranyl hydroxides in the transport and deposition of uranium in hydrothermal processes.

Effects of black soybean peel anthocyanins on the structural and functional properties of wheat gluten.

Wheat gluten (WG) is a crucial cereal protein commonly utilized in the food, biological and pharmaceutical industries. However, WG is poorly soluble in water, resulting in poor functional properties, which restrict its application in the food industry. As a result, there is an urgent need for improving the properties of WG. This study was conducted to examine the functional properties of WG after binding with black soybean peel anthocyanin extract (BAE). Results showed that BAE enhanced the solubility, water-holding and antioxidant capacity, foaming properties and emulsifying activity of WG, while decreasing the emulsion stability. The degree of hydrolysis of WG and retention rate of BAE became higher in the digested WG-BAE complex than in the control groups. Additionally, an analysis was conducted on the mechanism of interaction between cyanidin-3-O-glucoside (C3G) and WG/gliadin (Gli)/glutenin (Glu). The secondary structure of WG/Gli/Glu was altered after adding C3G. C3G had high affinity for WG/Gli/Glu since their binding constants were greater than 104 L mol-1. The primary binding forces between C3G and WG/Gli were hydrophobic interactions, whereas the main interaction forces between C3G and Glu were hydrogen bonding and van der Waals forces. Moreover, C3G increased the thermal stability and changed the network structure of WG/Gli/Glu. This study revealed that BAE effectively enhanced a range of functional properties of WG. The interaction between WG and BAE also improved the bioavailability and nutritional value of them. Furthermore, the interaction mode between BAE and WG was investigated. These findings lay a foundation for utilizing gluten-anthocyanins in the food sector. © 2024 Society of Chemical Industry.

Enhancing Acyclovir Permeability Using SLS Crosslinked β-Cyclodextrin Nanoparticles

Introduction/Objective: Acyclovir, a BCS class III drug (that has high solubility and low permeability) is an antiviral drug used for the treatment of herpes simplex and varicose zoster. To enhance acyclovir's permeability across the intestinal membrane and to improve its bioavailability the β-cyclodextrin (β-CD) nanoparticles of acyclovir were prepared with sodium lauryl sulfate (SLS) as a crosslinking agent. Methods: A phase solubility study was performed with varying ratios of acyclovir to β-CD. Three formulations of acyclovir-loaded β-CD nanoparticles were prepared with drug-β-CD ratios of 1:1, 1:2, and 1:4. The prepared nanoparticle formulations were characterized for FTIR, dynamic light scattering (particle size, polydispersity index, zeta potential) and in vitro permeability studies. Results: Phase solubility study resulted in an "AL type" curve with an association constant (Kc) of 12 M-1 which suggested the formation of a strong complex between acyclovir and β-CD, leading to enhanced solubility of acyclovir with increasing concentrations of β-CD. The FTIR spectrum confirmed the compatibility of acyclovir, β-CD, and SLS in the formulations. Dynamic light scattering analysis demonstrated particle sizes ranging from 152.92 nm to 335.7 nm, with the smallest particles in the 1:4 ratio formulation (152.92 nm), potentially due to higher drug encapsulation. Zeta potential measurements reflected formation of stable nanoparticle suspensions, with the formulation exhibiting a zeta potential of -45.4 mV showcasing optimal stability. In vitro permeation studies revealed that the 1:4 ratio formulation exhibited the highest permeability (84.24 ±1.94 % at the end of 150 min) through the eggshell membrane, implying efficient drug release. This increase in permeability corroborated with its smallest particle size. Conclusion: The study highlights the potential of β-CD nanoparticles (with best performance shown by drug-to-β-CD ratio 1:4) in augmenting acyclovir's delivery, suggesting a promising avenue for improving the drug delivery in viral infections.

Interaction of N-methylmesoporphyrin IX with a hybrid left-/right-handed G-quadruplex motif from the promoter of the SLC2A1 gene.

Left-handed G-quadruplexes (LHG4s) belong to a class of recently discovered noncanonical DNA structures under the larger umbrella of G-quadruplex DNAs (G4s). The biological relevance of these structures and their ability to be targeted with classical G4 ligands isunderexplored. Here, we explore whether the putative LHG4 DNA sequence from the SLC2A1 oncogene promoter maintains its left-handed characteristics upon addition of nucleotides in the 5'- and 3'-direction from its genomic context. We also investigate whether this sequence interacts with a well-established G4 binder, N-methylmesoporphyrin IX (NMM). We employed biophysical and X-ray structural studies to address these questions. Our results indicate that the sequence d[G(TGG)3TGA(TGG)4] (termed here as SLC) adopts a two-subunit, four-tetrad hybrid left-/right-handed G4 (LH/RHG4) topology. Addition of 5'-G or 5'-GG abolishes the left-handed fold in one subunit, while the addition of 3'-C or 3'-CA maintains the original fold. X-ray crystal structure analyses show that SLC maintains the same hybrid LH/RHG4 fold in the solid state and that NMM stacks onto the right-handed subunit of SLC. NMM binds to SLC with a 1:1 stoichiometry and a moderate-to-tight binding constant of 15 μM-1. Thiswork deepens our understanding of LHG4 structures and their binding with traditional G4 ligands.

New lanthanum (III) complexes containing azaphosphor β-diketon and diimine ligands: Synthesis, crystallography, morphology properties, DNA binding, DNA cleavage, and DFT calculation.

Two octa-coordinated lanthanum (III) complexes of deprotonated azaphosphor β-diketon and diimine ligands, [LnL3Q] (L=[Cl2CHC(O)NP(O)(NC6H12)2], Q=Phen (C1) and Bipy (C2)), were synthesized and characterized by elemental analysis, IR, and NMR spectra. X-ray crystallography revealed a distorted tetragonal antiprism LaO6N2 coordination geometry around the lanthanum atom in both compounds. Nano-sized complexes (Ć1 and Ć2) were synthesized via a sonochemical process and analyzed using SEM and XRPD. TGA-DTA analysis were performed on complexes in both bulk and nano scales. Redox behavior was also examined by cyclic voltammetry. The interaction between the complexes and calf thymus DNA (ct-DNA) was investigated using UV-Vis spectroscopy, fluorescence titration, viscosity measurements, and gel electrophoresis. C2 and Ć2 likely intercalate between DNA base pairs through van der Waals forces and hydrogen bonding, whereas C1 and Ć1 interact with DNA via groove binding. Further, result indicated the apparent association constant (Kapp) in the range of 4.53×104M-1-26.86×104M-1 with the highest value for nanocomplex Ć2. Fluorescence studies revealed dynamic and static quenching for C1, while the other compounds followed a static quenching process. Hirshfeld surface analysis and the NCI method were employed to demonstrate how non-covalent interactions influence the crystal packing through intermolecular interactions.

Highly Rigid, Yet Conformationally Adaptable, Bisporphyrin sp2-Cage Receptors Afford Outstanding Binding Affinities, Chelate Cooperativities, and Substrate Selectivities.

If we aim to develop efficient synthetic models of protein receptors and enzymes, we must understand the relationships of intra- and intermolecular interactions between hosts and guests and how they mutually influence their conformational energy landscape so as to adapt to each other to maximize binding energies and enhance substrate selectivities. Here, we introduce a novel design of cofacial (ZnII)bisporphyrin cages based on dynamic imine bonding, which is synthetically simple, but at the same time highly robust and versatile, affording receptors composed of only sp2-hybridized C and N atoms. The high structural rigidity of these cages renders them ideal hosts for ditopic molecules that can fit into the cavity and bind to both metal centers, leading to association constants as high as 109 M-1 in chloroform. These strong binding affinities are a consequence of the remarkable chelate cooperativities attained, with effective molarity (EM) values reaching record values over 103 M. However, we discovered that the cages can still adapt their structure to a more compact version, able to host slightly smaller guests. Such a conformational transition has an energy cost, which can be very different depending on the direction of the imine linkages in the cage skeleton and which results in EM values 2-3 orders of magnitude lower. This interplay between cooperativity and conformational adaptability leads to strong and unusual selectivities. Not only these metalloporphyrin receptors can choose to bind preferably to a particular guest, as a function of its size, but also the guest can select which host to bind, as a function now of the host's conformational rigidity. Such highly cooperative and selective associations are lost, however, in related flexible receptors where the imine bonds are reduced.

Investigation of Host-Guest Interactions in 2-Ureido-4-ferrocenylpyrimidine Derivatives.

In the present study, synthesis, conformational behavior, host-guest complex formation, and electrochemical properties of novel 6-substituted-2-ureido-4-ferrocenylpyrimidines were explored. A comprehensive NMR spectroscopic investigation was carried out to confirm the structure and conformational equilibrium of the ureidopyrimidines through studying the temperature- and concentration dependence of NMR spectra. Low-temperature NMR measurements were used to clarify structural changes inflicted by a 2,6-diaminopyridine guest. Association constant (Kassoc) values of host-guest complexes were calculated based on low-temperature titrations. It was shown that the introduction of a pyridin-2-yl substituent in the pyrimidine ring in host 10 induced a considerable change not only in the conformational equilibrium of the host itself but also in that of the host-guest complex. Geometries and relative stabilities of the conformers of host 10 as well as its host-guest complexes were determined by quantum chemical calculations. Electrochemical behavior of ureidopyrimidine hosts and host-guest complexes was investigated by cyclic voltammetry (CV) and linear sweep voltammetry (LSV) measurements. Two ureidopyrimidine derivatives were immobilized on the surface of spectral graphite electrodes, and their electrochemical response on the addition of 2,6-diaminopyridine was compared. These results also supported the importance of the pyridin-2-yl substituent in the efficient sensing of the guest.

Dual Fluorometric and Colorimetric Chemosensor Based on Poly(Arylene Ether Nitrile)s Functionalized Zn(II)Porphyrins for Selective Detection of Cyanide

AbstractPoly(arylene ether nitrile)s (PAENs) appended with Zn(II)‐porphyrin in varied molar percentages (5% and 10%) are developed as dual colorimetric and fluorometric sensors for highly sensitive and selective cyanide (CN−) detection. The materials, DP‐5%PAEN@Zn and DP‐10%PAEN@Zn, exhibit significant Soret band shifts at 420 ± 2 nm, accompanied by the appearance of a new absorption band at 436 ± 2 nm, indicating strong CN− binding with high association constants of 1.3 × 10⁴ M−¹ and 2.3 × 10⁴ M−¹, respectively. A prominent color change from purple to green allowed for naked eye detection. Spectrofluorimetric studies revealed turn‐off fluorescence with Stern‐Volmer constants (Ksv) of 99.85 × 103 M−¹ for DP‐5%PAEN@Zn and 121.08 × 103 M−¹ for DP‐10%PAEN@Zn, achieving limit of detection (LOD) of 0.177 and 0.099 ppb, respectively. DP‐10%PAEN@Zn demonstrated excellent sensitivity and selectivity toward CN−, and also reusability, as it remained functional after ten TFA treatment cycles. The mechanistic investigation, supported by photophysical, electrochemical, and DFT analyses, revealed a photoinduced electron transfer process via static quenching. Material stability is confirmed through photodegradability, prolonged time, temperature, and humidity testing. Prototype test kits are developed for real‐time visual CN− detection in remote and environmental samples (tap, lake, sewage, and soil). Additionally, a smartphone‐based color recognition assay is implemented for qualitative and quantitative analysis.

The inhibition of baicalein on pancreatic lipase investigated in vitro and in vivo

AbstractBackgroundObesity is increasing seriously worldwide. Inhibiting pancreatic lipase (PL) is an important way to prevent obesity. Baicalein, a dietary flavone, shows various physiological activities and has anti‐obesity potential. Therefore, the inhibitory activity of baicalein on PL was investigated in present study.ResultsBaicalein exhibited a significant inhibitory effect on PL with IC50 value of 68 μg/mL. Inhibition kinetics indicated that baicalein was a mixed‐type inhibitor of PL. Fluorescence titration showed that baicalein could induce fluorescence quenching of PL. The binding constant (logKa) and number of binding sites were calculated as 5.40 and 1.11, respectively. In addition, synchronous fluorescence analysis revealed that the quenching ratio of baicalein to tryptophan was greater than that of tyrosine. Circular dichroism (CD) spectrum showed that the binding of baicalein affected the secondary structure of the enzyme protein. Through molecular docking analysis, it confirmed that baicalein could interact with amino acid residues in lipase, thus reducing the enzyme catalytic activity. In vivo studies showed that oral administration of baicalein with a does of 50 mg/kg bwt significantly reduced fat absorption and increased its fecal excretion in rats.ConclusionBaicalein showed inhibitory activity on PL in both in vitro and in vivo studies. It may be a safe and effective dietary supplement for obesity prevention.

Insight into Stabilization of G-Quadruplex in c-MYC Region with Phenanthroimidazoisoindol-Acrylates and their Binding Behaviour towards Human Serum Albumin.

The interaction of G-quadruplex (non-canonical DNA) with suitable compounds for their stabilization at the promoter region of oncogenes has become a potential anticancer approach. We have studied the interaction of phenanthroimidazoisoindol-acrylates derivatives with c-MYC G-quadruplex. A series of 20 compounds were evaluated for their anticancer activity against human cancer cell lines, where compounds 3fa, 3ha, and 3ae have shown the broad-spectrum anticancer activities against most of the cancer cell lines and inactive towards normal cell lines. Various spectroscopic techniques have been used to study the interaction of these compounds. The studies reveal the strong binding of all three compounds with c-MYC G-quadruplex with significant selectivity over dsDNA, with binding constant of the order of 106 M-1. All three compounds bind effectively with HSA, which is a carrier protein, with binding constant of the order of 105 M-1. These results show that phenanthroimidazoisoindol-acrylate derivatives exhibit specificity towards G4 DNA, highlighting their potential as effective anticancer agents targeting the c-MYC G-quadruplex.