Relation between internal adaptation and degree of conversion of short-fiber reinforced resin composites applied in bulk or layered technique in deep MOD cavities.

OBJECTIVE: The purpose was to evaluate the degree of conversion (DC), internal adaptation (IA) and closed porosity (CP) of short-fiber reinforced resin composites (SFRC) associated with layered or bulk restorative procedures in deep MOD cavities. METHODS: Eighty third molars with standardized MOD cavities (5-mm-depth, 2.5-mm-width) were randomly divided into four groups and restored as follows: 1) bulk SFRC; 2) layered SFRC; 3) flowable bulk-fill resin-based composites (RBC); 4) layered conventional RBC. After one-month wet storage the samples were subjected to micro-computed tomography measurements and scanning electron microscopy to assess the IA and CP. Micro-Raman spectroscopy was used to determine the DC in different depths. Data were subjected to ANOVA and Tukey's post-hoc test, multivariate analysis and partial eta-squared statistics (p < 0.05). Pearson correlation coefficient was determined to assess the relationship among the parameters of interest. RESULTS: Gap/total interface volume ratio ranged between 0.22-0.47%. RBCs applied in bulk revealed significantly lower gap volume (p < 0.001) and CP (p < 0.05). Each group showed complete detachment on the pulpal and partial on the lateral walls, except for group3. While the highest DC% was achieved by the conventional RBC (87.2%), followed by the flowable bulk-fill (81.2%), SFRC provided the best bottom to top DC ratio (bulk: 96.4%, layered: 98.7%). The effect of factors studied (RBC type, filling technique) on IA and DC was significant (p < 0.001). SIGNIFICANCE: Bulk placement of RBCs exhibited lower interfacial gap volume and achieved satisfactory DC without significant correlation between these parameters. Incremental insertion of SFRC had no advantage over bulk placement in terms of IA and DC.

Self-Driven Gr/WSe2/Gr Photodetector with High Performance Based on Asymmetric Schottky van der Waals Contacts.

Two-dimensional (2D) self-driven photodetectors have a wide range of applications in wearable, imaging, and flexible electronics. However, the preparation of most self-powered photodetectors is still complex and time-consuming. Simultaneously, the constant work function of a metal, numerous defects, and a large Schottky barrier at the 2D/metal interface hinder the transmission and collection of optical carriers, which will suppress the optical responsivity of the device. This paper proposed a self-driven graphene/WSe2/graphene (Gr/WSe2/Gr) photodetector with asymmetric Schottky van der Waals (vdWs) contacts. The vdWs contacts are formed by transferring Gr as electrodes using the dry-transfer method, obviating the limitations of defects and Fermi-level pinning at the interface of electrodes made by conventional metal deposition methods to a great extent and resulting in superior dynamic response, which leads to a more efficient and faster collection of photogenerated carriers. This work also demonstrates that the significant surface potential difference of Gr electrodes is a crucial factor to ensure their superior performance. The self-driven Gr/WSe2/Gr photodetector exhibits an ultrahigh Ilight/Idark ratio of 106 with a responsivity value of 20.31 mA/W and an open-circuit voltage of 0.37 V at zero bias. The photodetector also has ultrafast response speeds of 42.9 and 56.0 µs. This paper provides a feasible way to develop self-driven optoelectronic devices with a simple structure and excellent performance.

A New Application of Spin and Fluorescence Double-Sensor Molecules.

EPR imaging techniques are known to be successful tools for mapping living bodies, especially because of the high transparency of tissues in the microwave range. This technique assumes the presence of radicals whose in vivo transport is also controlled by serum albumins. Accordingly, in this study, the interactions between 3-hydroxymethyl-1-oxyl-4-(pyren-1-yl)-2,2,5,5-tetramethyl-2,5-dihydro-1H-pyrrole radical and the human serum albumin molecules were investigated. To clarify the adsorption processes of this radical onto the surface of human serum albumin (HSA), the interaction of the OMe derivative of the radical was also examined parallel with the studies on the radical-HSA interactions. Considering the solubility issues and also to modulate the transport, inclusion complexes of the radical with a cavitand derivative were also studied. The latter interactions were observed through fluorescence spectroscopy, fluorescence polarization, and by EPR spectroscopy. As a double-sensor molecule, we found that the fluorophore nitroxide is a good candidate as it gave further information about host-guest interactions (fluorescence, fluorescence polarization, and EPR). We also found that in the presence of a cavitand, a complex with greater stability was formed between the sensor molecule and the human serum albumin. Based on these observations, we can conclude that applying this double-sensor (spin, fluorescent) molecule is useful in cases when different interactions can affect the EPR measurements.

Effect of Ceramic and Dentin Thicknesses and Type of Resin-Based Luting Agents on Intrapulpal Temperature Changes during Luting of Ceramic Inlays.

The adhesive cementation of ceramic inlays may increase pulpal temperature (PT) and induce pulpal damage due to heat generated by the curing unit and the exothermic reaction of the luting agent (LA). The aim was to measure the PT rise during ceramic inlay cementation by testing different combinations of dentin and ceramic thicknesses and LAs. The PT changes were detected using a thermocouple sensor positioned in the pulp chamber of a mandibular molar. Gradual occlusal reduction obtained dentin thicknesses of 2.5, 2.0, 1.5, and 1.0 mm. Light-cured (LC) and dual-cured (DC) adhesive cements and preheated restorative resin-based composite (RBC) were applied to luting of 2.0, 2.5, 3.0, and 3.5 mm lithium disilicate ceramic blocks. Differential scanning calorimetry was used to compare the thermal conductivity of dentin and ceramic slices. Although ceramic reduced heat delivered by the curing unit, the exothermic reaction of the LAs significantly increased it in each investigated combination (5.4-7.9 °C). Temperature changes were predominantly influenced by dentin thickness followed by LA and ceramic thickness. Thermal conductivity of dentin was 24% lower than that of ceramic, and its thermal capacity was 86% higher. Regardless of the ceramic thickness, adhesive inlay cementation can significantly increase the PT, especially when the remaining dentin thickness is <2 mm.

The effect of high-irradiance rapid polymerization on degree of conversion, monomer elution, polymerization shrinkage and porosity of bulk-fill resin composites.

OBJECTIVE: The purpose was to compare the degree of conversion (DC), monomer elution (ME), polymerization shrinkage (PS) and porosity of two addition-fragmentation chain transfer (AFCT) modified resin-based composites (RBC) light-cured with rapid- (RP), turbo- (TP) or conventional polymerization (CP) settings. METHODS: Cylindrical samples (6-mm wide, 4-mm thick) were prepared from Tetric PowerFill (TPF) and Filtek One Bulk (FOB). Four groups were established according to the polymerization settings: 3s-RP, 5s-TP, 10s-CP and 20s-CP. Samples in 1 mm thickness with 20s-CP settings served as controls. The DC at the top and bottom surfaces was measured with micro-Raman spectroscopy. ME was detected with high-performance liquid chromatography. PS and porosity were analyzed by micro-computed tomography. ANOVA and Tukey's post-hoc test, multivariate analysis and partial eta-squared statistics were used to analyze the data (p < 0.05). RESULTS: FOB showed higher DC values (61.5-77.5 %) at the top compared to TPF (43.5-67.8 %). At the bottom TPF samples achieved higher DCs (39.9-58.5 %) than FOB (18.21-66.18 %). Extending the curing time increased DC (except the top of FOB) and decreased ME. BisGMA release was the highest among the detected monomers from both RBCs. The amount was three-fold more from TPF. The factor Material and Exposure significantly influenced DC and ME. PS (1.8-2.5 %) did not differ among the groups and RBCs except for the lowest value of TPF cured with the 3s_RP setting (p = 0.03). FOB showed 4.5-fold lower porosity (p < 0.001). Significantly higher pore volume was detected after polymerization in 3s_RP (p < 0.001). SIGNIFICANCE: High-irradiance rapid 3-s curing of AFCT modified RBCs resulted in inferior results for some important material properties. A longer exposure time is recommended in a clinical situation.

Anodic Polymerization of Phenylphenols in Methyl Isobutyl Ketone and Mesityl Oxide: Incorporation of a Cavitand into the Layers Formed for Sensing Phenols in Organic Media.

The electropolymerization of three phenylphenol isomers was studied in methyl isobutyl ketone and mesityl oxide, and the remarkable differences highlighted the importance of the carbon-carbon double bond in mesityl oxide. In the case of each substrate, a brownish deposit formed during the electrooxidation. The obvious difference between the polymers formed from the two solvents was recognized via voltammetric signal enhancement of 4-methoxyphenol and 4-chlorophenol, and it was only observed in the case of mesityl oxide. The experiments highlighted that incorporation of a cavitand with biphenyl groups on the upper rim of the polymers of phenylphenols improved the results to a small extent. The cavitand was, itself, electroactive without any fouling effect. As 2-phenylphenol is by far the cheapest of the three isomers, a cavitand was incorporated into its polymer, which was exploited to solve analytical problems while mesityl oxide was used as solvent. Useful quantifications were achieved in organic solvents; however, it failed under aqueous conditions due to the high hydrophobicity of the deposit. Application of differential pulse voltammetry for 4-methoxyphenol and 4-chlorophenol gave detection limits of 9.28 and 50.8 µM in acetonitrile, respectively. This procedure resulted in the immobilization of cavitand derivatives onto the electrode's surface, and the layer formed offered selective sensing of phenols by electrochemical methods.

Influence of Aliphatic Chain Length on Structural, Thermal and Electrochemical Properties of n-alkylene Benzyl Alcohols: A Study of the Odd-Even Effect.

The century-old, well-known odd-even effect phenomenon is still a very attractive and intriguing topic in supramolecular and nano-scale organic chemistry. As a part of our continuous efforts in the study of supramolecular chemistry, we have prepared three novel aromatic alcohols (1,2-bis[2-(hydroxymethyl)phenoxy]butylene (Do4OH), 1,2-bis[2-(hydroxymethyl)phenoxy]pentylene (Do5OH) and 1,2-bis[2-(hydroxymethyl)phenoxy]hexylene (Do6OH)) and determined their crystal and molecular structures by single-crystal X-ray diffraction. In all compounds, two benzyl alcohol groups are linked by an aliphatic chain of different lengths (CH2)n; n = 4, 5 and 6. The major differences in the molecular structures were found in the overall planarity of the molecules and the conformation of the aliphatic chain. Molecules with an even number of CH2 groups tend to be planar with an all-trans conformation of the aliphatic chain, while the odd-numbered molecule is non-planar, with partial gauche conformation. A direct consequence of these structural differences is visible in the melting points-odd-numbered compounds of a particular series display systematically lower melting points. Crystal and molecular structures were additionally studied by the theoretical calculations and the melting points were correlated with packing density and the number of CH2 groups. The results have shown that the generally accepted rule, higher density = higher stability = higher melting point, could not be applied to these compounds. It was found that the denser packaging causes an increase in the percentage of repulsive H‧‧‧H interactions, thereby reducing the stability of the crystal, and consequently, the melting points. Another interesting consequence of different molecular structures is their electrochemical and antioxidative properties-a non-planar structure displays the highest oxidation peak of hydroxyl groups and moderate antioxidant activity.

Interactions of resveratrol and its metabolites (resveratrol-3-sulfate, resveratrol-3-glucuronide, and dihydroresveratrol) with serum albumin, cytochrome P450 enzymes, and OATP transporters.

Resveratrol (RES) is a widely-known natural polyphenol which is also contained by several dietary supplements. Large doses of RES can result in high micromolar levels of its sulfate and glucuronide conjugates in the circulation, due to the high presystemic metabolism of the parent polyphenol. Pharmacokinetic interactions of RES have been extensively studied, while only limited data are available regarding its metabolites. Therefore, in the current study, we examined the interactions of resveratrol-3-sulfate (R3S), resveratrol-3-glucuronide, and dihydroresveratrol (DHR; a metabolite produced by the colon microbiota) with human serum albumin (HSA), cytochrome P450 (CYP) enzymes, and organic anion transporting polypeptides (OATP) employing in vitro models. Our results demonstrated that R3S and R3G may play a major role in the RES-induced pharmacokinetic interactions: (1) R3S can strongly displace the site I marker warfarin from HSA; (2) R3G showed similarly strong inhibitory action on CYP3A4 to RES; (3) R3S proved to be similarly strong (OATP1B1/3) or even stronger (OATP1A2 and OATP2B1) inhibitor of OATPs tested than RES, while R3G and RES showed comparable inhibitory actions on OATP2B1.

Voltammetric and Fluorimetric Studies of Dibenzoylmethane on Glassy Carbon Electrodes and Its Interaction with Tetrakis (3,5-Dicarboxyphenoxy) Cavitand Derivative.

Due to the medical importance of dibenzoylmethane, one of the aims of the study was to find an appropriate packing material and a biologically friendly co-solvent to help its introduction into living systems. Accordingly, redox properties of dibenzoylmethane were investigated on glassy carbon electrodes in acetonitrile and in 1-propanol with cyclic voltammetry, and showed a diffusion-controlled process. In the anodic window, an oxidation peak appeared at around 1.9 V in both solvents. Cycling repeatedly between 0 and 2 V, the reproducibility of this peak was acceptable, but when extending the window to higher potentials, the electrode deactivated, obviously due to electrode material. The addition of the investigated tetrakis(3,5-dicarboxyphenoxy) cavitand did not significantly change the voltammograms. Further electrochemical experiments showed that the coexistence of water in acetonitrile and 1-propanol drastically reduces the solubility of dibenzoylmethane. Moreover, very rapid electrode deactivation occurred and this fact made the use of electrochemical methods complicated. Considering that both the cavitand and dibenzoylmethane are soluble in dimethyl sulfoxide, the interaction of these species was investigated and formation of stable complexes was detected. This observation was verified with fluorescence quenching studies. The mixture of water and dimethyl sulphoxide also dramatically improved the solubility of the cavitand-dibenzoylmethane complex at high excess of water. The addition of cavitand improved the solubility of dibenzoylmethane, a property which supports the application of dibenzoylmethane in therapy.

Detection of Residual 2-Phenylphenol on Lemon Rind by Electrochemically Deposited Poly(hydroxybenzaldehyde) and Poly(hydroxybenzoic acid) Polymeric Stackings as Electrode Modifiers.

This study explores the characteristics of electrodeposition of the three hydroxybenzaldehyde isomers and selected hydroxybenzoic acids (4-hydroxybenzoic acid, salicylic acid, 3,5-dihydroxybenzoic acid) from mesityl oxide solvent. Similar to recent advances of this solvent, used by electrochemical studies, the carbon-carbon double bond had significant influence on the formation of polymers from the outlined molecules. In case of most substrates the peak currents increased to a steady-state but electropolymerization of some substrates caused significant deactivation. Scanning electron microscopic and complementary voltammetric studies facilitated that the electrochemically formed polymers are present on the electrode surface in stackings. In viewpoint of analysis of 2-phenylphenol, the modifying deposit formed from 4-hydroxybenzaldehyde was the best with 5 µM detection limit obtained with differential pulse voltammetry. Furthermore, a new procedure was chosen for the involvement of a cavitand derivative into the organic layers with the purpose to improve the layer selectivity (subsequent electrochemical polymerization in an other solution). Further studies showed that in this way the sensitivities of as-modified electrodes were a little worse than without this step, thus indicating that application of this step is disadvantageous. Recovery studies of 2-phenylphenol were carried out on lemon rind without any treatment, and it was compared with the case when the outer yellow layer was removed by rasping. The inner tissues showed very high adsorption affinity towards 2-phenylphenol.

Temperature-Induced Change of Water Structure in Aqueous Solutions of Some Kosmotropic and Chaotropic Salts.

The hydrogen bond structure of water was examined by comparing the temperature dependent OH-stretching bands of water and aqueous NaClO4, KClO4, Na2SO4, and K2SO4 solutions. Results called attention to the role of cations on top of the importance of anions determining the emerging structure of a multi-layered system consisting single water rings or multi-ring water-clusters.

Weak Interactions of the Isomers of Phototrexate and Two Cavitand Derivatives.

The interactions of two conformers of newly synthesized photoswitchable azobenzene analogue of methotrexate, called Phototrexate, with two cavitand derivatives, have been investigated in dimethyl sulfoxide medium. Photoluminescence methods have been applied to determine the complex stabilities and the related enthalpy and entropy changes associated to the complex formation around room temperature. Results show opposite temperature dependence of complex stabilities. The structure of the upper rims of the host molecules and the reordered solvent structure were identified as the background of the opposite tendencies of temperature dependence at molecular level. These results can support the therapeutic application of the photoswitchable phototrexate, because the formation of inclusion complexes is a promising method to regulate the pharmacokinetics of drug molecules.

Pre-Heating Effect on Monomer Elution and Degree of Conversion of Contemporary and Thermoviscous Bulk-Fill Resin-Based Dental Composites.

Detection of unreacted monomers from pre-heated resin-based dental composites (RBC) is not a well-investigated topic so far. The objectives were to determine the temperature changes during the application and polymerization, the degree of conversion (DC) and unreacted monomer elution of room temperature (RT), and pre-heated thermoviscous [VisCalor Bulk(VCB)] and high-viscosity full-body contemporary [Filtek One Bulk(FOB)] bulk-fill RBCs. The RBCs' temperatures during the sample preparation were recorded with a K-type thermocouple. The DC at the top and bottom was measured with micro-Raman spectroscopy and the amounts of eluted BisGMA, UDMA, DDMA, and TEGDMA were assessed with High-Performance Liquid Chromatography. The temperatures of the pre-heated RBCs decreased rapidly during the manipulation phase. The temperature rise during photopolymerization reflects the bottom DCs. The differences in DC% between the top and the bottom were significant. RT VCB had a lower DC% compared to FOB. Pre-heating did not influence the DC, except on the bottom surface of FOB where a significant decrease was measured. Pre-heating significantly decreased the elution of BisGMA, UDMA, DDMA in the case of FOB, meanwhile, it had no effect on monomer release from VCB, except TEGDMA, which elution was decreased. In comparison, RBC composition had a stronger influence on DC and monomer elution, than pre-cure temperature.

Comparative EPR Study on the Scavenging Effect of Methotrexate with the Isomers of Its Photoswitchable Derivative.

The scavenging effect of the antimetabolite dihydrofolate reductase inhibitor methotrexate (MTX) and the isomers of its photoswitchable derivate, cis- and trans-phototrexate (PHX), have been compared by ESR spectroscopy, with the application of a cyclic hydroxylamine spin probe. The results showed the most pronounced scavenging effect in the presence of trans-phototrexate (trans-PHX). At a low concentration (100 µM) cis-PHX also showed a greater scavenging effect than the parent molecule MTX. Direct antioxidant properties of the investigated molecules were measured by ABTS scavenging assay, which showed no significant difference between trans-PHX and cis-PHX, but both of the isomers of PHX showed a higher antioxidant capacity than MTX. These findings imply that trans-PHX may have more pronounced anti-inflammatory and tissue-protective effects than MTX, despite the lack of its cytotoxic, antineoplastic effect.

Effects of Microenvironmental Changes on the Fluorescence Signal of Alternariol: Magnesium Induces Strong Enhancement in the Fluorescence of the Mycotoxin.

Alternariol (AOH) is an emerging mycotoxin produced by Alternaria molds. It occurs as a contaminant e.g., in oilseeds, cereals, grapes, and tomatoes. Chronic exposure to AOH may cause genotoxic and endocrine disruptor effects. Our recent studies demonstrated that the fluorescence signal of AOH can be strongly affected by the environmental pH as well as by the presence of serum albumin or cyclodextrins. In the current study, we aimed to characterize the most optimal circumstances regarding the highly sensitive fluorescent detection of AOH. Therefore, the further detailed investigation of the microenvironment on the fluorescence signal of the mycotoxin has been performed, including the effects of different buffers, organic solvents, detergents, and cations. Organic solvents (acetonitrile and methanol) caused only slight increase in the emission signal of AOH, while detergents (sodium dodecyl sulfate and Triton-X100) and Ca2+ induced considerably higher enhancement in the fluorescence of the mycotoxin. In addition, Mg2+ proved to be a superior fluorescence enhancer of the AOH. Spectroscopic and modeling studies suggest the formation of low-affinity AOH-Mg2+ complexes. The effect of Mg2+ was also tested in two HPLC assays: Our results show that Mg2+ can considerably increase the fluorescence signal of AOH even in a chromatographic system.

Degree of conversion and in vitro temperature rise of pulp chamber during polymerization of flowable and sculptable conventional, bulk-fill and short-fibre reinforced resin composites.

OBJECTIVE: Determine the degree of conversion (DC) and in vitro pulpal temperature (PT) rise of low-viscosity (LV) and high-viscosity (HV) conventional resin-based composites (RBC), bulk-fill and short-fibre reinforced composites (SFRC). METHODS: The occlusal surface of a mandibular molar was removed to obtain dentine thickness of 2 mm above the roof of the pulp chamber. LV and HV conventional (2 mm), bulk-fill RBCs (2-4 mm) and SFRCs (2-4 mm) were applied in a mold (6 mm inner diameter) placed on the occlusal surface. PT changes during the photo-polymerization were recorded with a thermocouple positioned in the pulp chamber. The DC at the top and bottom of the samples was measured with micro-Raman spectroscopy. ANOVA and Tukey's post-hoc test, multivariate analysis and partial eta-squared statistics were used to analyze the data (p < 0.05). RESULTS: The PT changes ranged between 5.5-11.2 °C. All LV and 4 mm RBCs exhibited higher temperature changes. Higher DC were measured at the top (63-76%) of the samples as compared to the bottom (52-72.6%) in the 2 mm HV conventional and bulk-fill RBCs and in each 4 mm LV and HV materials. The SFRCs showed higher temperature changes and DC% as compared to the other investigated RBCs. The temperature and DC were influenced by the composition of the material followed by the thickness. SIGNIFICANCE: Exothermic temperature rise and DC are mainly material dependent. Higher DC values are associated with a significant increase in PT. LV RBCs, 4 mm bulk-fills and SFRCs exhibited higher PTs. Bulk-fills and SFRCs applied in 4 mm showed lower DCs at the bottom.

Interaction of silymarin components and their sulfate metabolites with human serum albumin and cytochrome P450 (2C9, 2C19, 2D6, and 3A4) enzymes.

Silymarin is a mixture of flavonolignans isolated from the fruit of milk thistle (Silybum marianum (L.) Gaertner). Milk thistle extract is the active ingredient of several medications and dietary supplements to treat liver injury/diseases. After the oral administration, flavonolignans are extensively biotransformed, resulting in the formation of sulfate and/or glucuronide metabolites. Previous studies demonstrated that silymarin components form stable complexes with serum albumin and can inhibit certain cytochrome P450 (CYP) enzymes. Nevertheless, in most of these investigations, silybin was tested; while no or only limited information is available regarding other silymarin components and metabolites. In this study, the interactions of five silymarin components (silybin A, silybin B, isosilybin A, silychristin, and 2,3-dehydrosilychristin) and their sulfate metabolites were examined with human serum albumin and CYP (2C9, 2C19, 2D6, and 3A4) enzymes. Our results demonstrate that each compound tested forms stable complexes with albumin, and certain silymarin components/metabolites can inhibit CYP enzymes. Most of the sulfate conjugates were less potent inhibitors of CYP enzymes, but 2,3-dehydrosilychristin-19-O-sulfate showed the strongest inhibitory effect on CYP3A4. Based on these observations, the simultaneous administration of high dose silymarin with medications should be carefully considered, because milk thistle flavonolignans and/or their sulfate metabolites may interfere with drug therapy.

Solvent dependent 4-aminosalicylic acid-sulfamethazine co-crystal polymorph control.

Despite polymorphism of crystalline active pharmaceutical ingredients (APIs) being a common phenomenon, reports on polymorphic co-crystals are limited. As polymorphism can vastly affect API properties, controlling polymorph generation is crucial. Control of the polymorph nucleation through the use of different solvents during solution crystallization has been used to obtain a desirable crystal polymorph. There have been two reported polymorphic forms of the 4-aminosalicylic acid-sulfamethazine co-crystals. These forms were found to have different thermodynamic stabilities. However, the control of co-crystal polymorph generation using preparation parameter manipulation has never been reported. The aim of this study was to establish the effect of different solvent parameters on the formation of different co-crystal polymorphic forms. Selection of the solvents was based on Hansen Solubility Parameters (HSPs) as solvents with different solubility parameters are likely to interact differently with APIs, ultimately affecting co-crystallization. Eight solvents with different HSPs were used to prepare co-crystals by solvent evaporation at two different temperatures. Through characterization of the co-crystals, a new polymorph has been obtained. The hydrogen bond acceptability seemed to affect the co-crystal form obtained more than the hydrogen bond donation ability. Furthermore, the use of HSPs can be utilized as an easy calculation method in screening and design of co-crystals.

Effect of methotrexate and its photodegradation products on the temperature induced denaturation of human serum albumin.

Effect of the photodegradation of chemotherapeutic agent methotrexate on the denaturation of human serum albumin has been studied by differential scanning calorimetry and fluorimetric measurements. Photoluminescence studies highlighted entropy driven binding of both methotrexate molecules and its degradation products to the albumin molecules. The calorimetric measurements evaluated by the Kissinger method show elevated activation energy in the presence of methotrexate. Similar but moderated enhancement of the activation energy was obtained in the presence of the photodegradation products of methotrexate. These results highlight stabilization of the human serum albumin by the methotrexate drug which finding may contribute to fine tuning of methotrexate applications in therapy.

Interactions of zearalanone, α-zearalanol, ß-zearalanol, zearalenone-14-sulfate, and zearalenone-14-glucoside with serum albumin.

The xenoestrogenic mycotoxin zearalenone is a Fusarium-derived food and feed contaminant. In mammals, the reduced (e.g., zearalanone, α-zearalanol, and ß-zearalanol) and conjugated (e.g., zearalenone-14-sulfate) metabolites of zearalenone are formed. Furthermore, filamentous fungi and plants are also able to convert zearalenone to conjugated derivatives, including zearalenone-14-sulfate and zearalenone-14-glucoside, respectively. Serum albumin is the dominant plasma protein in the circulation; it interacts with certain mycotoxins, affecting their toxicokinetics. In a previous investigation, we demonstrated the remarkable species differences regarding the albumin binding of zearalenone and zearalenols. In the current study, the interactions of zearalanone, α-zearalanol, ß-zearalanol, zearalenone-14-sulfate, and zearalenone-14-glucoside with human, bovine, porcine, and rat serum albumins were examined, employing fluorescence spectroscopy and affinity chromatography. Zearalanone, zearalanols, and zearalenone-14-sulfate form stable complexes with albumins tested (K = 9.3 × 103 to 8.5 × 105 L/mol), while the albumin binding of zearalenone-14-glucoside seems to be weak. Zearalenone-14-sulfate formed the most stable complexes with albumins examined. Considerable species differences were observed in the albumin binding of zearalenone metabolites, which may have a role in the interspecies differences regarding the toxicity of zearalenone.