Exploring host-guest interactions of sulfobutylether-ß-cyclodextrin and phenolic acids by chemiluminescence and site-directed molecular docking.

We have developed a rapid method that allows us to characterize the binding interaction of sulfobutylether-ß-cyclodextrin (SBE-ß-CD) with five therapeutically important phenolic acids: ferulic acid, caffeic acid, gallic acid, protocatechuic acid, and vanillic acid. The method utilizes a flow-injection chemiluminescence (FI-CL) technique that relies on the inhibition of a cyclodextrin-luminol chemiluminescence (CL) by increasing amounts of the phenolic acids (PAs). This loss of CL with increasing amounts of PAs fits the equation lg[(I0-Is)/Is]=lgKPAs+nlg[PAs], allowing calculation of the binding constant (KPAs) and stoichiometric ratio (n). The five phenolic acids and SBE-ß-CD formed complexes with a stoichiometric ratio of 1:1. The binding constants were on the order of 10(7) M(-1). These results showed a good correlation with the scores calculated by molecular docking. Further investigation by site-directed molecular docking and linear correlation analysis revealed that PAs entered the larger cavity of SBE-ß-CD and the formation constants mainly depended on the number of hydrogen bond acceptors in the PAs structures. All these results indicate that the CL-based affinity method can be used for direct determination of host-guest inclusion interactions and has great potential to become a reliable alternative for quantitatively studying host-guest binding and drug-protein interactions.

Study on the interaction of catalase with pesticides by flow injection chemiluminescence and molecular docking.

The interaction mechanisms of catalase (CAT) with pesticides (including organophosphates: disulfoton, isofenphos-methyl, malathion, isocarbophos, dimethoate, dipterex, methamidophos and acephate; carbamates: carbaryl and methomyl; pyrethroids: fenvalerate and deltamethrin) were first investigated by flow injection (FI) chemiluminescence (CL) analysis and molecular docking. By homemade FI-CL model of lg[(I0-I)/I]=lgK+nlg[D], it was found that the binding processes of pesticides to CAT were spontaneous with the apparent binding constants K of 10(3)-10(5) L mol(-1) and the numbers of binding sites about 1.0. The binding abilities of pesticides to CAT followed the order: fenvalerate>deltamethrin>disulfoton>isofenphos-methyl>carbaryl>malathion>isocarbophos>dimethoate>dipterex>acephate>methomyl>methamidophos, which was generally similar to the order of determination sensitivity of pesticides. The thermodynamic parameters revealed that CAT bound with hydrophobic pesticides by hydrophobic interaction force, and with hydrophilic pesticides by hydrogen bond and van der Waals force. The pesticides to CAT molecular docking study showed that pesticides could enter into the cavity locating among the four subdomains of CAT, giving the specific amino acid residues and hydrogen bonds involved in CAT-pesticides interaction. It was also found that the lgK values of pesticides to CAT increased regularly with increasing lgP, Mr, MR and MV, suggesting that the hydrophobicity and steric property of pesticide played essential roles in its binding to CAT.

Determination of picogram quantities of chlortoluron in soil samples by luminol-chitosan chemiluminescence system.

Based on the enhancing effect of chitosan (CS) on luminol-dissolved oxygen chemiluminescence (CL) reaction, a flow injection (FI) luminol-CS CL system was established. It was found that the increase of CL intensity was proportional to the concentrations of CS ranging from 0.7 to 10.0 µmol l(-1). In the presence of chlortoluron (CTU), the CL intensity of luminol-CS system could be obviously inhibited and the decrements of CL intensity were linearly proportional to the logarithm of CTU concentrations ranging from 0.01 to 70.0 ng ml(-1), giving the limit of detection 3.0 pg ml(-1) (3σ). At a flow rate of 2.0 ml min(-1), the whole process including sampling and washing could be accomplished within 36 s, offering a sample throughput of 100 h(-1). The proposed FI-CL method was successfully applied to the determination of CTU in soil samples with recoveries ranging from 95.0 % to 105.3 % and the relative standard deviations (RSDs) of less than 4.0 %.

Revealing interaction between sulfobutylether-ß-cyclodextrin and reserpine by chemiluminescence and site-directed molecular docking.

The host-guest interaction between sulfobutylether-ß-cyclodextrin (SBE-ß-CD) and reserpine (RSP) is described using flow injection-chemiluminescence (FI-CL) and site-directed molecular docking methods. It was found that RSP could inhibit the CL intensity produced by a luminol/SBE-ß-CD system. The decrease in CL intensity was logarithmic over an RSP concentration range of 0.03 to 700.0 nM, giving a regression equation of ∆I = 107.1lgCRES + 186.1 with a detection limit of 10 pM (3σ). The CL assay was successfully applied in the determination of RSP in injection, saliva and urine samples with recoveries in the range 93.5-106.1%. Using the proposed CL model, the binding constant (KCD-R ) and the stoichiometric ratio of SBE-ß-CD/RSP were calculated to be 7.4 × 10(6) M(-1) and 1 : 1, respectively. Using molecular docking, it was confirmed that luminol binds to the small cavity of SBE-ß-CD with a nonpolar interaction, while RSP targeted the larger cavity of SBE-ß-CD and formed a 1 : 1 complex with hydrogen bonds. The proposed new CL method has the potential to become a powerful tool for revealing the host-guest interaction between CDs and drugs, as well as monitoring drugs with high sensitivity.

A method of chemiluminescence coupled with ultrafiltration for investigating the interaction between ibuprofen and human serum albumin.

In acidic media, ibuprofen substantially enhanced the weak chemiluminescence (CL) produced by sodium sulfite and potassium permanganate. The increased signals were linearly correlated with ibuprofen concentrations ranging from 1.2 × 10(-3) to 4.8 µM, with a detection limit of 4.8 × 10(-4) µM. Two ultrafiltration (UF) membranes were used to construct a unit for trapping 0.15 and 0.75 µM human serum albumin (HSA) and coupled online with the CL system. At low HSA concentrations, the numbers of bound molecules per binding site were calculated to be 0.9 for Sudlow site I and 6.2 for Sudlow site II. The association constants on these binding sites were 5.9 × 10(5) and 3.4 × 10(4) M(-1), respectively. Our CL-UF protocol presents a rapid and sensitive method for studies on drug-protein interaction.

One-step method for plasma determination of ibuprofen by chemiluminescence-coupled ultrafiltration and application in a pharmacokinetic study.

A simple one-step method is established for plasma determination of ibuprofen and its pharmacokinetic study. The method involves simple sample pre-treatment by dilution, rapid separation by ultrafiltration (UF) and online sensitive detection by chemiluminescence (CL) based on significant intensity enhancement of ibuprofen on the weak CL of potassium permanganate and sodium sulphite in an acidic system. The calibration curve for ibuprofen is linear in the range 0.1-50.0 µg/mL in rat plasma. Average recoveries of ibuprofen at 0.80, 12.0 and 40.0 µg/mL amounted to 98.0 ± 4.2%, 101.2 ± 3.6% and 99.3 ± 5.4%, respectively. Standard deviations of intra- and inter-day measurement precision and accuracy are within ±10.0%. The detection limit for ibuprofen is 10.0 µg/L in plasma samples. Pharmacokinetic study of ibuprofen by the validated method shows that the mean plasma drug concentration-time course confirms to a classical two-compartment open model with first-order absorption. The proposed method will be an alternative for pre-clinical pharmacokinetic study of ibuprofen and other non-steroidal anti-inflammatory drugs.

A new sensitive flow-injection chemiluminescence method for the determination of H(2)-receptor antagonists.

Based on the chemiluminescence (CL) intensity generated from the potassium ferricyanide [K(3)Fe(CN)(6)]-rhodamine 6G system in sodium hydroxide (NaOH) medium, a new sensitive flow-injection chemiluminescence (FI-CL) method has been developed, validated and applied for the determination of three kinds of H(2)-receptor antagonists: cimetidine (CIMT), ranitidine (RANT) hydrochloride and famotidine (FAMT). Under the optimum conditions, the linear range for the determination was 1.0 x 10(-9)-7.0 x 10(-5) g/ml for CIMT, 1.0 x 10(-9)-5.0 x 10(-5) g/mL for RANT hydrochloride and 5.0 x 10(-9)-7.0 x 10(-5) g/mL for FAMT. During 11 repeated measurements of 1.0 x 10(-6) g/mL sample solutions, the relative standard deviations (RSDs) were all <5%. The detection limit was 8.56 x 10(-10) g/mL for CIMT, 8.69 x 10(-10) g/mL for RANT hydrochloride and 2.35 x 10(-9) g/mL for FAMT (S:N = 3). This method has been successfully implemented for the analysis of H(2)-receptor antagonists in pharmaceuticals.