Complexation Constants Research Articles

Reevaluation for UV photolysis of Fe(III) inducing tetracycline abatement: Overlooked significance of complexation-assistance in environmental fates of antibiotics

Interaction of antibiotics with metal ions in aquatic environments, commonly occurring to form complexes, may affect the migration, transformation and reactivity of residual antibiotics. This study demonstrates the photolysis of Fe(III) by UV irradiation at pH 3.5, as an advanced oxidation process, to produce •OH for the abatement of a common broad-spectrum antibiotic compound, tetracycline (TET). The dimethylamino (-N(CH3)2) and hydroxyl (-OH) groups of TET were determined as the binding sites for the complexation with Fe(III) via a series of novel characterization approaches. The complexation stoichiometry of Fe(III)-TET complexation, including the complexation ratio, constants and percentages, was determined via a complexometric titration based on the UV differential spectroscopy. The complexation constant was determined to be 21,240 ± 1745 L·mol−1 under the designed conditions. Complexation of TET with Fe(III) enhanced its degradation in the UV/Fe(III) process, through the promotion of the •OH generation by inhibiting hydrolysis-precipitation process of Fe(III) and enhancing Fe(III)/Fe(II) cycle and the acceleration of mass transfer between •OH and TET. This finding provides new insights into the role of complexation in the fate of residual antibiotics in the UV/Fe(III) process. The reduced overall ecotoxicity during the TET abatement, evaluated by the toxicity variation through ECOSAR program, provides the UV/Fe(III) process with a theoretical feasibility for water decontamination in actual applications.

ESIPT-based fluorescent enhanced probes prompted by methylated β-cyclodextrin for the detection of thiophenols

Thiophenol and its derivatives are compounds with high toxicity to organisms and environmental pollution, so it is necessary to detect the level of thiophenols in the environment and biological samples. The probes 1a-b were obtained by introducing the 2,4-dinitrophenyl ether group into diethylcoumarin–salicylaldehyde based compounds. And they can form host-guest compounds with methylated β-cyclodextrin (M-β-CD), the association constants of inclusion complexes are 49.2 M−1, 125 M−1 respectively. The fluorescence intensities of probes 1a-b at 600 nm (1a) and 670 nm (1b) increased significantly in thiophenols detection. Meanwhile, with the addition of M-β-CD, the hydrophobic cavity of M-β-CD significantly increased the fluorescence intensity of probes 1a-b, thus the detection limits of probes 1a-b to thiophenols were reduced from 410 nM, 365 nM to 62 nM, 33 nM respectively. Whereas, the good selectivity and short response time of probes 1a-b towards thiophenols was not affected in the presence of M-β-CD. Moreover, probes 1a-b were used for further water sample detection and HeLa cell imaging experiments due to their good response to thiophenols and the results suggested that probes 1a-b had the potential to detect the content of thiophenols in water samples and living cells.

Cylindrical first-order superintegrability with complex magnetic fields

This article is a contribution to the study of superintegrable Hamiltonian systems with magnetic fields on the three-dimensional Euclidean space E3 in quantum mechanics. In contrast to the growing interest in complex electromagnetic fields in the mathematical community following the experimental confirmation of its physical relevance [Peng et al., Phys. Rev. Lett. 114, 010601 (2015)], they were so far not addressed in the growing literature on superintegrability. Here, we venture into this field by searching for additional first-order integrals of motion to the integrable systems of cylindrical type. We find that already known systems can be extended into this realm by admitting complex coupling constants. In addition to them, we find one new system whose integrals of motion also feature complex constants. All these systems are multiseparable. Rigorous mathematical analysis of these systems is challenging due to the non-Hermitian setting and lost gauge invariance. We proceed formally and pose the resolution of these problems as an open challenge.

Gold-Reducing Cathode Reactions Kinetics in Acid Thiourea Electrolytes

The kinetics of cathode reactions occurring on a gold electrode in acidic thiourea-citrate electrolytes has been studied. Using classical electrochemical methods (potentiometry, chronovoltammetry, electrogravimetry) and graphic-analytical calculations, the following were established: the instability constant of gold complexes, the type of kinetics, the nature of the delayed stage, and the main kinetic characteristics of the electrochemical reaction during gold deposition.

Kinetics of reactive extraction of free fatty acids in jatropha oil with monoethanolamine in methanol: A key biodiesel pre-processing step

Unrefined vegetable oils and fats contain free fatty acids and they ought to be minimized for use in food and non-food applications. Traditional deacidification of vegetable oils and fats adopts alkali neutralization for the removal of free fatty acids. Here, a simple method for the removal of free fatty acids from jatropha oil by reactive extraction using monoethanolamine in methanol is proposed. Reactive extraction kinetic studies with initial free fatty acids concentration (0.1–0.5 kmol/m3) using monoethanolamine (0.4141–1.6568 kmol/m3) in methanol at 30 °C was performed and investigated. Parameters like distribution coefficient, equilibrium complexation constant for free fatty acids extraction were obtained to arrive at equilibrium and kinetic conclusions. Most importantly, the criteria for reaction regime was established through Hatta number. The study revealed that reactive extraction of free fatty acids using monoethanolamine in methanol falls under reaction regime 2. The study demonstrated that reactive extraction was highly successful in reduction of the free fatty acids in jatropha oil. Further biodiesel was prepared using the deacidified oil and the specifications obtained were well within the standard ASTM limits.

Back Accumulation of Diffusive Gradients in Thin-Films Devices with a Stack of Resin Discs To Assess Availability of Metal Cations to Biota in Natural Waters.

Determining species, concentrations, and physicochemical parameters in natural waters is key to improve our understanding of the functioning of these ecosystems. Diffusive Gradients in Thin-films (DGT) devices with different thicknesses of the resin or of the diffusive disc can be used to collect independent information on relevant parameters. In particular, DGT devices with a stack of two resin discs offer a simple way to determine dissociation rate constants of metal complexes from the accumulation of the target metal in the back resin disc. In this work, simple approximate expressions for the determination of the dissociation rate constant are reported and applied to a model Ni nitrilotriacetic complex as well as to Zn complexes in the Mediterranean Osor stream. Once the physicochemical parameters are known, one can plot the labile fraction of the metal complexes in terms of the thickness of the diffusion domain. These plots reveal a strong dependence on the nature of complexes as well as on the characteristics of the diffusion domain, and they are of high interest as predictors of availability to biota whose uptake is limited by diffusion.

Modifications of geldanamycin via CuAAC altering affinity to chaperone protein Hsp90 and cytotoxicity

Functionalization of alkyne (1) and azide (2) derivatives of geldanamycin (GDM) via dipolar cycloaddition CuAAC yielded 35 new congeners (3–37) with C(17)-triazole arms bearing caps of different nature (basic vs. acidic, hydrophilic vs. hydrophobic). Confrontation of biological data (anticancer activity vs. toxicity in normal cells) with lipophilicity (clogP), dissociation constants (Kd) of complexes with Hsp90 and binding modes to Hsp90 revealed SAR in specific subgroups of GDM derivatives. The most potent GDM congeners 14–16, bearing C(17)-triazole-benzyl-halogen arms exhibited the most optimal clogP values of 2.7–3.1 at favourable binding to Hsp90 (KdHsp90 at μM level). The anticancer activity of 14–16 (IC50 = 0.23–0.41 μM) is higher than those of GDM (IC50 = 0.58–0.64 μM) and actinomycin D (ActD, IC50 = 0.62–0.71 μM) in SKBR-3, SKOV-3 and PC-3 cell lines, with a comparable cytotoxicity in healthy cells. The relationship between structure and attractive anticancer potency (IC50 = 0.53–0.74 μM) is also observed for congeners with C(17)-triazole-saccharide or C(17)-triazole-unsaturated arms. In the former, the absolute configuration at C(4) (ᴅ-glucose vs. ᴅ-galactose) whereas in the latter the length of the unsaturated arm influences the cytotoxic effects due to different binding strength (Kd, ΔE) and modes with Hsp90. Among all triazole congeners of GDM that are biologically attractive and exhibit lower toxicity in normal cells than GDM and ActD, the derivative 22, bearing the C(17)-triazole-cinnamyl arm, shows the lowest Kd (Hsp90), optimal clogP = 2.82, the best pro-apoptotic properties in SKBR-3 and SKOV-3 and the best selectivity indices (SI). For the most potent GDM derivatives with C(17)-triazole arm, the docking studies have suggested the importance of the intermolecular stabilization between the arm and the D57 or Y61 of Hsp90.

PH-metric titration technique for the study of metal-complexes of substituted 2- Oxo-2H-Chromene-3-Carbohydrazide derivatives in solution: calculation of stability constants

Background: In coordination chemistry, the stability of complexes is expressed in terms of the formation constant of complexes. In coordination complexes, the temperature is very important. It plays an important role in complex formation reaction. Temperature affects metal-ligand stability constant (log K) and proton-ligand stability constant (pK). The metal ion Mn2+, Co2+, Ni2+, and Cu2+ at different temperatures form complexes with 4-sulfamethoxazoleazo-3-methyl-2-pyrazolin-5-one are reported. The metal-ligand stability constant (logK) and proton-ligand stability constant (pK) of Mn(II), Co(II), Ni(II), Cu(II), and Zn(II) with organic ligand n-[2-hydroxy-1-napthalydene]-2-methylanilline at 0.1 M ionic strength in 60% dioxane-water medium is studied. The study of thermodynamic parameters and stability constant of complexes of substituted thiazole Schiff bases with rare earth metal ions in mixed solvent is reported. Objective: The study of coordination compounds and a lot of work has been done on metal-ligand stability constant. The same transition metal ion form complexes with substituted pyrazole for this metal-ligand stability constant are determined. Method: Pointwise Calculation Method Half Integral Method. Result: The values of logK1 and logK2 are determined from the metal-ligand formation curve at formation numbers 0.5 and 1.5. In all cases, logK1 is greater than logK2. The ratio logK1/logK2 is positive and greater than one in all systems. This implies that there is little or no steric hindrance to the addition of the secondary ligand molecules. The difference between logK1 - logK2 is usually positive. If the difference between logK1 and logK2 is less than 2.5, simultaneous formation of 1:1 and 1:2 complexes occurs and if it is more than 2.5, then stepwise complex formation occurs. In the present case, in all systems, it is less than 2.5. This indicates the simultaneous formation of 1:1 and 1:2 complexes takes place. Conclusion: A pH-metric study of Substituted 2-oxo-2H-chromene-3-carbohydrazide derivatives with metal ions Fe(III), and Mn(II) occurs. The graphical representation of the curve shows that the acid + ligand curve is separated from the corresponding acid + ligand + metal curve in this system. The formation of a complex is indicated. Half integral method and pointwise calculation method give nearly similar results. The values of stability constants for all systems indicate that the complexes formed in these processes are stable.

Dynamic retention of thallium(I) on humic acid: Novel insights into the heterogeneous complexation ability and responsiveness

Widely distributed soil humic acid (HA) would significantly affect the environmental migration behavior of Tl(I), but a quantitative and mechanistic understanding of the dynamic Tl(I) retention process on HA is limited. A unified kinetic model was established by coupling the humic ion-binding model with a stirred-flow kinetic model, which quantified the complexation constants and responsiveness coefficients during dynamic Tl(I)-HA complexation. Furthermore, the heterogeneous complexation mechanism of HA and Tl(I) was revealed by batch adsorption experiments, stirred-flow migration experiments, and 2D-FTIR-COS analysis. An increase in pH significantly improved the responsiveness of HA organic binding sites, promoting Tl(I) dynamic retention. Monodentate carboxyl groups induced rapid Tl(I) complexation (kd = 1.9 min−1) in strongly acidic environments. Under weakly acidic conditions, Tl(I) retention on HA was mainly attributed to the synergistic complexation effect of carboxyl and amide groups. Among the groups, multidentate carboxyl-phenolic hydroxyl sites could achieve sustained Tl(I) retention due to their stable complexing properties (logK = 4.48∼7.46) and slow response (kd = 1.1 × 10−3 min−1). These findings are crucial for a comprehensive understanding of the environmental interactions of Tl(I) with humic substances in swamp environments.

Elucidation of binding dynamics of tyrosine kinase inhibitor tepotinib, to human serum albumin, using spectroscopic and computational approach

Tepotinib (TPT), an anticancer drug, is a fibroblast growth factor receptor inhibitor approved by the FDA for the chemotherapy of urothelial carcinoma. The binding of anticancer medicines to HSA can affect their pharmacokinetics and pharmacodynamics. The absorption, fluorescence emission, circular dichroism, molecular docking, and simulation studies were used to evaluate the binding relationship between TPT and HSA. The absorption spectra exhibited a hyperchromic effect upon the interaction of TPT with HSA. The Stern-Volmer and binding constant of the HSA-TPT complex demonstrates that fluorescence quenching is triggered by a static rather than a dynamic process. Further, the displacement assays and molecular docking results revealed that TPT preferred binding to site III of HSA. Circular dichroism spectroscopy confirmed that TPT binding to HSA induces conformational changes and reduces α-helical content. The thermal CD spectra reveal that tepotinib enhances protein's stability in the temperature range of 20 to 90 °C. The findings of MDS studies provide further evidence for the stability of the HSA-TPT complex. Consequently, the findings of the present investigation provide a clear picture of the impacts of TPT on HSA interaction. These interactions are thought to make the microenvironment around HSA more hydrophobic than in its native state.

A Rhodamine B-Salicylic Acid Compound with Colorimetric /Fluorescent Dual Channel Response for the Identification of Fe3+

In this paper, a rhodamine B-salicylic acid based binary compound probe RB-SA was designed and synthesized, and its structure was characterized by 1HNMR and 13CNMR. The probe provides a colorimetric/fluorescent dual-channel response to Fe3+ in the aqueous phase. Under the induction of Fe3+, the spirolactam ring of the probe RB-SA changed from closed loop to open loop, and a new absorption peak appeared at 560 nm and the solution color changed from colorless to red, while the fluorescence signal turned on, and the fluorescence intensity at 587 nm increased linearly with the addition of Fe3+. It was shown that the probe RB-SA exhibited high sensitivity to Fe3+, with a minimum detection limit (LOD) of 5.19 nM and a complexation constant of 1.03 × 104 M-1 based on fluorescence spectroscopy titration data.

Effect of calcium and trace metals (Cd, Cu, Mn, Ni, Zn) on root iron uptake in relation to chemical properties of the root-excreted ligands.

Interferences of major cations (Ca2+, Mg2+) and trace metals (TM, i.e. Cd2+, Cu2+, Mn2+, Ni2+ and Zn2+) in root Fe uptakewere evaluated. Root Fe uptake was modelled including the reactions of the root exuded ligand with the soil major and trace cations. Fe uptake was simulated with different ligands representing various affinities for the cations, the latter varying in concentration. The stability constant of Fe complexes (KFeL) does not influence Fe uptake, contrarily to the ligand parameters for Fe-hydroxide dissolution. Fe uptake decreases when KCaL or Ca2+ in solution increases. Presence of TM has nearly no influence on Fe uptake when the TM complexes have low stability constants (KML), as in the case of oxalate and citrate complexes. When ligands have high KML, like EDTA, DFO-B or mugineic acid (MA), TM reduces Fe uptake by 51-55%, and much more in the case of TM contamination. Exudation of Fe ligands with low KML has no negative effect on TM uptake, which can increase if the dissociation rate is high, as for Cu complexes. Ligands with high KML (EDTA, DFO-B, MA) greatly reduce TM uptake, only if their hydrated cations can be absorbed. Calcium does not significantly reduce Fe uptake when Ca-complexes have KCaL < 104. Consequently, ligands like oxalate or MA should be efficient in most soils. TM should perturbate Fe uptake mediated by ligands with high KML such as MA, but not oxalate. Plants exuding phytosiderophores should also absorb TM complexes to avoid micronutrient deficiencies.

An asymptotic homogenization formula for complex permittivity and its application

The $\mathbb R$-linear boundary value problem in a multiply connected domain on a flat torus is considered. This problem is closely related to the Riemann-Hilbert problem on analytic functions. The considered problem arises in the homogenization procedure of random media with complex constants which express the permittivity of components. A new asymptotic formula for the effective permittivity tensor is derived. The formula contains location of inclusions in symbolic form. The application of the derived formula to investigation of the morphology of the tumor cells in disordered biological media is discussed.

Sintesis dan Uji Fotostabilitas Kompleks Zn(II)-Astaxanthin

Astaxanthin is a pigment from the carotenoid group found in algae, shrimp, and crabs. Due to its chemical structure, astaxanthin has many health benefits but low stability against direct exposure to light and oxygen. In this study, the Zn-astaxanthin complex was synthesized using a reflux reactor at 37o and 60oC. Complex compounds were analyzed using a UV-Vis spectrophotometer and FTIR. The UV-Vis spectrophotometer analysis showed a bathochromic shift in acetone (475 to 477 nm). In comparison, in dimethyl sulfoxide, a hypsochromic shift (493 to 475 nm) was observed, and a new absorption peak was observed at 330 nm. FTIR analysis shows a decrease in the intensity of the C=O stretching vibration and -OH group vibration at 1712 and 1219 cm-1, respectively. This indicated an interaction between the metal ion Zn2+ and astaxanthin. Zn-astaxanthin has better stability than astaxanthin during irradiation, using a halogen lamp at a light intensity of 300 W/m2 for 6 hours. Based on the zero-order degradation kinetics model, the degradation rate constant of the Zn-astaxanthin complex was 0.0621, smaller than that of astaxanthin (0.0880).

Pyrrolidine-Derived Phenanthroline Diamides: An Influence of Fluorine Atoms on the Coordination of Lu(III) and Some Other f-Elements and Their Solvent Extraction.

Three pyrrolidine-derived phenanthroline diamides were studied as ligands for lutetium trinitrate. The structural features of the complexes have been studied using various spectral methods and X-ray. The presence of halogen atoms in the structure of phenanthroline ligands has a significant impact on both the coordination number of lutetium and the number of solvate water molecules in the internal coordination sphere. The stability constants of complexes with La(NO3)3, Nd(NO3)3, Eu(NO3)3, and Lu(NO3)3 were measured to demonstrate higher efficiency of fluorinated ligands. NMR titration was performed for this ligand, and it was found that complexation with lutetium leads to an approximately 13 ppm shift of the corresponding signal in the 19F NMR spectrum. The possibility of formation of a polymeric oxo-complex of this ligand with lutetium nitrate was demonstrated. Experiments on the liquid-liquid extraction of Am(III) and Ln(III) nitrates were carried out to demonstrate advantageous features of chlorinated and fluorinated pyrrolidine diamides.

Macrocyclic Compounds Comprising Tris(3-Aminopropyl)Amine Units and Fluorophore Moieties: Synthesis and Spectroscopic Studies in the Presence of Metal Salts

The synthesis of a variety of polyazamacrocyclic compounds comprising structural units of tris(3-aminopropyl)amine (TRPN) and oxadiamines, decorated with one or two fluorophore groups (dansyl or quinoline) at different nitrogen atoms, was carried out using Pd(0)-catalyzed amination. The dependence of the yields of the macrocycles on the synthetic path was observed. The spectrophotometric and fluorescent properties of the target compounds were studied, and their coordination with metal cations using UV–vis, fluorescence spectra as well as NMR titration was investigated. The stoichiometry and binding constants of several complexes with Cu(II), Zn(II), Cd(II), Pb(II) and Hg(II) were established. Three of the six studied macrocycles can be judged as prospective detectors of Zn(II) cations due to the substantial enhancement of fluorescence.

Solubilities of heavy rare earth sulfates in water (gadolinium to lutetium) and H2SO4 solutions (dysprosium)

Solubilities of rare earth element (REE) sulfates are critical in hydrometallurgical process development for REE extraction, but measurements are notably lacking for heavy REE sulfates. Therefore, solubilities of heavy REE sulfates are measured for binary REE2(SO4)3–H2O systems from 25 to 95 °C for gadolinium through lutetium. Solubility isotherms are also determined for the ternary Dy2(SO4)3–H2SO4–H2O system at 25–95 °C and 0.05–0.5 M H2SO4. Saturating solid phases are identified by X-ray diffraction and thermogravimetric analyses. For all REEs, the octahydrates, REE2(SO4)3•8H2O, are the equilibrium saturating solid phases at 25–95 °C. Solubilities decrease strongly with increasing temperature, indicative of exothermic heats of solution for REE sulfate octahydrates. Within the REE series, solubilities increase markedly (an order of magnitude) from gadolinium through lutetium sulfate. Changes in solubilities are juxtaposed with stability constants for REE sulfate complexes, REESO4+ and REE(SO4)2−. As these species are inner-sphere complexes, water of hydration is released from REE3+ during complex formation which increases water activity. Hence, heavy REEs with larger complex stability constants also display lower solubilities, and vice versa. In sulfuric acid solutions, dysprosium sulfate solubility increases and passes through a maximum with increasing sulfuric acid concentration, as with other REE sulfates. The maximum solubility is postulated to relate to the dissociation constant of bisulfate (HSO4−), which passes through a minimum with increasing sulfuric acid concentration. The formation of bisulfate consumes some free sulfate thereby increasing REE sulfate solubility.

Modelling the reaction of uranium with carboxylic groups on surfaces through mono- and multi- dentate surface complexes on the basis of pH and redox potential

An analytical expression is proposed to simulate effects of pH and redox potential (E) on the sorption of uranium onto bioorganic model particles in saline or other aquatic environments. The elaborated expression is intended to avoid use of the classical approach of sorption which relies on experimental data and empirical models. The goal is to produce an expression that provides a distribution coefficient (Kd e.g. mL g−1) as function of pH, E and ligand concentration (through complex formation in solution) by applying a surface complexation model on one type of mono-dentate surface sites> (SuOH) as well as utilizing multi-dentate surface sites> (SuOH)c. The formulation of the worked out expression makes use of correlations between the surface complexation and hydrolysis constants for all species and sorption sites. The model was applied to the sorption of uranium onto bioorganic sites with and without carbonates in solution e.g. Log Kd: + 2.75 at pH 8 for 2 sites per nm2. The calculated distribution coefficients were found very sensitive to the presence of carbonates, e.g. Log Kd: − 7.0 at pH 8 for 2 × 10−3 M total carbonate. The potential reduction of uranium U(VI) and its complexes (carbonates) which are the primary stable species in surface waters, to U(IV) during sorption was simulated in association with a decrease in the redox potential and was found generally below the redox stability limits of water. The calculated distribution coefficient values were validated by the values reported in literature for the sorption of uranium onto specific adsorbents. The investigated simulations are also applicable to the sorption of other redox sensitive elements.

Kinetic Model and Mechanism of Heterogeneous Hydrogenation of Strained Polycyclic Compounds Derived from 5-Vinyl-2-norbornene

The main pathways of liquid-phase hydrogenation of 5-ethenylbicyclo[2.2.1]hept-2-ene (5-vinyl-2-norbornene, VNE) in the presence of PK-25 palladium catalyst (Pd/γ-Al2O3, 0.25% Pd) were studied. All the reaction products were identified, and the material balance was examined. The effect of the prevalent adsorption of the norbornene double bond on the Pd active site (AS) was confirmed. The parallel-consecutive scheme of the process mechanism, based on the set of experimental and theoretical data, was suggested. It involves the successive substrate hydrogenation and significant role of the isomerization of the vinyl group into the ethylidene group in intermediates on AS in a hydrogen atmosphere. The reaction is zero-order in a wide interval of initial VNE concentrations. An adequate kinetic model of the process, based on the Langmuir–Hinshelwood approach and the concept of multiple adsorption of substrates on one AS, was developed. Five steps, including two parallel steps, significantly contribute to the reaction rate. Their rate constants and the adsorption constants of AS complexes with unsaturated compounds were estimated.

Novel Regioselective Synthesis of 1,3,4,5-Tetrasubstituted Pyrazoles and Biochemical Valuation on F1FO-ATPase and Mitochondrial Permeability Transition Pore Formation.

An efficient, eco-compatible, and very cheap method for the construction of fully substituted pyrazoles (Pzs) via eliminative nitrilimine-alkene 1,3-dipolar cycloaddition (ENAC) reaction was developed in excellent yield and high regioselectivity. Enaminones and nitrilimines generated in situ were selected as dipolarophiles and dipoles, respectively. A deep screening of the employed base, solvent, and temperature was carried out to optimize reaction conditions. Recycling tests of ionic liquid were performed, furnishing efficient performance until six cycles. Finally, a plausible mechanism of cycloaddition was proposed. Then, the effect of three different structures of Pzs was evaluated on the F1FO-ATPase activity and mitochondrial permeability transition pore (mPTP) opening. The Pz derivatives' titration curves of 6a, 6h, and 6o on the F1FO-ATPase showed a reduced activity of 86%, 35%, and 31%, respectively. Enzyme inhibition analysis depicted an uncompetitive mechanism with the typical formation of the tertiary complex enzyme-substrate-inhibitor (ESI). The dissociation constant of the ESI complex (Ki') in the presence of the 6a had a lower order of magnitude than other Pzs. The pyrazole core might set the specific mechanism of inhibition with the F1FO-ATPase, whereas specific functional groups of Pzs might modulate the binding affinity. The mPTP opening decreased in Pz-treated mitochondria and the Pzs' inhibitory effect on the mPTP was concentration-dependent with 6a and 6o. Indeed, the mPTP was more efficiently blocked with 0.1 mM 6a than with 1 mM 6a. On the contrary, 1 mM 6o had stronger desensitization of mPTP formation than 0.1 mM 6o. The F1FO-ATPase is a target of Pzs blocking mPTP formation.