Sándor Kunsági-Máté

Flavonoid aglycones can compete with Ochratoxin A for human serum albumin: A new possible mode of action

The mycotoxin Ochratoxin A (OTA) appears worldwide in cereals, plant products, different foods and drinks. Ochratoxin A binds to plasma albumin with a very high affinity. However, it is well known that natural flavonoids can also bind to human serum albumin (HSA) at the same binding site as OTA does (site I, subdomain IIA). A few experimental literature data suggest that reducing the bound fraction of OTA speeds up its elimination rate with a potential decrease in its toxicity. In our experimental model competitive binding properties of flavonoid aglycones were examined with a fluorescence polarization based approach. Our data show that some of the flavonoids are able to remove the toxin from HSA. We conclude that among the 13 studied flavonoid aglycones galangin and quercetin were the most effective competitors for OTA.

Host-guest interaction of calixarene molecules with neutral benzotrifluorides Comparison of luminescence spectral data with results of model calculations relating to complex formation

The ‘host’ properties of calix[4]arene and 4- tert-butyl-calix[6]arene molecules under the effect of different neutral pesticide related trifluoromethyl-benzene molecules as ‘guests’ have been investigated by spectrofluorometric method. Significant dependence of the photoluminescence behaviour of calixarene derivatives on the structure of interactive molecules was detected in chloroform and dimethylformamide solvent. The formation of stable host‐guest complexes was checked by quantum-chemical method. The results show that the photoluminescence signal reflects the supramolecular interaction. This makes calixarenes promising candidates as host molecules to be used in chemical sensors measuring neutral organic molecules.

Fluorescence spectroscopic investigation of competitive interactions between ochratoxin A and 13 drug molecules for binding to human serum albumin

Ochratoxin A (OTA) is a highly toxic mycotoxin found worldwide in cereals, foods, animal feeds and different drinks. Based on previous studies, OTA is one of the major causes of the chronic tubulointerstitial nephropathy known as Balkan endemic nephropathy (BEN) and exerts several other adverse effects shown by cell and/or animal models. It is a well-known fact that OTA binds to various albumins with very high affinity. Recently, a few studies suggested that reducing the bound fraction of OTA might reduce its toxicity. Hypothetically, certain drugs can be effective competitors displacing OTA from its albumin complex. Therefore, we examined 13 different drug molecules to determine their competing abilities to displace OTA from human serum albumin (HSA). Competitors and ineffective chemicals were identified with a steady-state fluorescence polarization-based method. After characterization the competitive abilities of individual drugs, drug pairs were formed and their displacing activity were tested in OTA-HSA system. Indometacin, phenylbutazone, warfarin and furosemide showed the highest competing capacity but ibuprofen, glipizide and simvastatin represented detectable interaction too. Investigations of drug pairs raised the possibility of the presence of diverse binding sites of competing drugs. Apart from the chemical information obtained in our model, this explorative research might initiate future designs for epidemiologic studies to gain further in vivo evidence of long-term (potentially protective) effects of competing drugs administered to human patients.

Coordination of methanol clusters to benzene: A computational study

Benzene-methanol cluster structures were investigated with theoretical chemistry methods to describe the microsolvation of benzene and the benzene-methanol azeotrope. Benzene-methanol (MeOH) clusters containing up to six methanol molecules have been calculated by ab initio [MP2/6-311++G(d,p)//MP2/6-31+G(d,p) + BSSE correction] method. The BSSE was found quite large with this basis set, hence, different extrapolation schemes in combination with the aug-cc-pVxZ basis sets have been used to estimate the complete basis set limit of the MP2 interaction energy [ΔE(MP2/CBS)]. For smaller clusters, n ≤ 3, DFT procedures (DFTB+, MPWB1K, M06-2X) have also been applied. Geometries obtained for these clusters by M06-2X and MP2 calculations are quite similar. Based on the MP2/CBS results, the most stable C(6)H(6)(MeOH)(3) cluster is characterized by a hydrogen bonded MeOH trimer chain interacting with benzene via π···H-O and O···H-C(benzene) hydrogen bonds. Larger benzene-MeOH clusters with n ≥ 4 consist of cyclic (MeOH)(n) subclusters interacting with benzene by dispersive forces, to be denoted by C(6)H(6) + (MeOH)(n). Interaction energies and cooperativity effects are discussed in comparison with methanol clusters. Besides MP2/CBS calculations, for selected larger clusters the M06-2X/6-311++G(d,p)//M06-2X/6-31+G(d,p) procedure including the BSSE correction was also used. Interaction energies obtained thereby are usually close to the MP2/CBS limit. To model the benzene-MeOH azeotrope, several structures for (C(6)H(6))(2)(MeOH)(3) clusters have been calculated. The most stable structures contain a tilted T-shaped benzene dimer interacting by π···H-O and O···H-C (benzene) hydrogen bonds with a (MeOH)(3) chain. A slightly less negative interaction energy results for a parallel displaced benzene sandwich dimer with a (MeOH)(3) chain atop of one of the benzene molecules.

Permittivity-dependent entropy driven complexation ability of cone and paco tetranitro-calix[4]arene toward para-substituted phenols.

Considering the importance of the polarizability of the rings of calixarenes in the entropy-driven interaction processes, we examined the effect of entropy compensation on the complex formation of cone and partial cone (paco) conformers of tetranitro-calix [4]arene, possessing O-ethyl substituents at the lower rim. Both calixarene conformers were fully characterized including X-ray crystallography. Various para-substituted phenols were used as guest molecules. Photoluminescence (PL) measurements and quantum-chemical (QC) investigations were used. A permittivity dependence of the molecular interactions was obtained in different alcohols as solvents. It was found that the cone conformer of the title calixarene derivative forms stable complexes with all phenols of the p-substituted series. The free enthalpy changes show very high complex stability of cone calixarene with p-nitro and p-chloro-substituted phenols. In the cases of parent phenol, p-cresol and p- tBu-phenol, the stability is significantly lower; however, it slightly increases with the increasing electron density on the aromatic ring of guest molecules. Similarly, the entropy changes are significantly different for these two separated groups: the entropy changes obtained in the former cases are nearly the same, while large differences in the formation entropy were obtained in the latter cases. Both the experimental and theoretical investigations revealed that no considerable interaction exists between phenols and the paco conformer of the title calixarene. It is probably due to the locking of the calixarene cavity by the bent O-ethyl chain.

Investigation of the interaction of calixarene (host) and neutral benzotrifluoride (guest): Comparison of luminescence characteristics of calixarenes with results of model calculations relating to complex formation

Abstract The ‘host’ properties of calix[4]arene and 4- tert -butyl-calix[6]arene molecules under the effect of different neutral pesticide related trifluoromethyl-benzene (benzotrifluoride) molecules as ‘guests’ have been investigated by spectrofluorometric method. Photoluminescence signal was detected in chloroform and dimethylformamide solvents. The characteristics of the photoluminescence (intensity and anisotropy decay) of calixarene derivatives show significant changes in presence of benzotrifluorides. The host–guest interaction and complex formation were described by quantum-chemical method. The results show that the photoluminescence signal reflects the supramolecular interaction. This makes calixarenes promising candidates as host molecules to be used in chemical sensors measuring neutral organic molecules.

Cavity shaped host-guest interaction of distally dialkylated calix[4]arenes with 1-chloro-4-(trifluoromethyl)benzene

Abstract The conformation of the conic molecular cavity in the ‘host’ properties of 1,3 dialkylated calixarenes were examined by spectrofluorometric and quantum-chemical methods. The size of the ‘host’ molecular cavity was influenced by the nature of substituents in distal position. As model guest molecule, 1-chloro-4-(trifluoromethyl)benzene (BTF) from the pesticide related organic series was chosen. The dependence of the interaction between the neutral molecule and the calixarene on the extent of distorsion in the conformation of ‘host’ cavity was obtained. The ‘pinched cone’ conformer of 1,3-substituted calix[4]arenes seems to form a complex with electron-deficient neutral aromatics by predominant π–π type in-teraction.

Interaction of mycotoxin zearalenone with human serum albumin

Zearalenone (ZEN) is a mycotoxin produced mainly by Fusarium species. Fungal contamination of cereals and plants can result in the formation of ZEN, leading to its presence in different foods, animal feeds, and drinks. Because ZEN is an endocrine disruptor, it causes reproductive disorders in farm animals and hyperoestrogenic syndromes in humans. Despite toxicokinetic properties of ZEN were studied in more species, we have no information regarding the interaction of ZEN with serum albumin. Since albumin commonly plays an important role in the toxicokinetics of different toxins, interaction of ZEN with albumin has of high biological importance. Therefore the interaction of ZEN with human serum albumin (HSA) was investigated using spectroscopic methods, ultrafiltration, and molecular modeling studies. Fluorescence spectroscopic studies demonstrate that ZEN forms complex with HSA. Binding constant (K) of ZEN-HSA complex was quantified with fluorescence quenching technique. The determined binding constant (logK=5.1) reflects the strong interaction of ZEN with albumin suggesting the potential biological importance of ZEN-HSA complex formation. Based on the results of the investigations with site markers as well as docking studies, ZEN occupies a non-conventional binding site on HSA. Considering the above listed observations, we should keep in mind this interaction if we would like to precisely understand the toxicokinetic behavior of ZEN.

Application of the Quantum Cluster Equilibrium (QCE) model for the liquid phase of primary alcohols using B3LYP and B3LYP-D DFT methods.

The Quantum Cluster Equilibrium (QCE) model was applied to the liquid phase for the first few members of the homologous series of unbranched aliphatic primary alcohols, methanol, ethanol, propan-1-ol, and butan-1-ol. Cluster structures and energies were calculated by density functional theory [B3LYP/6-311++G(2d,2p)]. For butan-1-ol the dispersion interaction was also considered with the B3LYP-D method. In agreement with previous findings, cyclic cluster structures are the most probable ones. In addition, weak C-H...O interactions as well as dispersion interactions between the longer alkyl chains were found to be important in the cluster formation. The reliability of the model was assessed by the calculated constant pressure heat capacity (C(p)) values. Larger deviations between theory and experiment were found for higher homologes (propan-1-ol, butan-1-ol) with the B3LYP method. When the B3LYP-D method was applied for butan-1-ol, adequate agreement was found between experimental and calculated C(p) values.

Effect of Molecular Environment on the Formation Kinetics of Complexes of Malvidin-3-O-glucoside with Caffeic Acid and Catechin

The formation kinetics of malvidin-polyphenol copigmentation complexes was studied in water-ethanol mixtures by time-dependent recording of the photoluminescence (PL) signal of malvidin. Two reaction channels were examined according to the order of complex formation. Both channels end with the same malvidin-polyphenol complexes formed in binary mixtures of water-ethanol. However, in the first case, the malvidin-polyphenol complexes are formed in water first, and then their solvation shells are altered according to the changed composition of the bulk solutions after the aqueous solution is diluted with ethanol. In the second case, the stock solutions are prepared as binary solvent mixtures; therefore, the bicomponent solvation shells of the interacted species are formed prior to molecular association. Our results show a faster formation of the complexes in the former case. Evaluation of the Arrhenius parameters of the reaction shows that the activation energy of the first reaction channel is lower and the frequency factor is higher, supporting a higher reaction rate. These observations are applicable to a wide range of chemistry where the molecular environment is composed of binary solutions. In particular, it has significant consequences for winemaking procedures, where one method of color improvement is based on the association of the species examined in this work.