Szupramolekuláris rendszerek fotofizikai és fotokémiai tulajdonságai = Photophisical and photochemical properties of supramolecular systems

Fotoaktív vegyületek (olyan anyagok, amelyek alkalmazása optikai tulajdonságain alapul) tulajdonságait tanulmányoztuk oldatfázisban és szupramolekuláris komplexekben, UV-látható abszorpciós, fluoreszcencia és CD spektroszkópiai mérésekkel, továbbá időfelbontásos lézerspektroszkópiai kísérletekkel. Az eredményeket több esetben kvantumkémiai számítások alapján értelmeztük. Kutatásaink eredményeként - új modellt állítottunk fel fluoreszkáló kationos festékek orientációs relaxációjára oldatban, - fluoreszcens próbaként alkalmazható vegyületek gerjesztett elektronállapotait vizsgálva tisztáztuk a dezaktíválódási folyamatok mechanizmusát, - jellemeztük fémionok optikai kimutatására szolgáló szupramolekuláris receptorok ionmegkötésének szelektivítását, és királis ligandumok megkötésére szolgáló szupramolekuláris receptorok enantioszelektivítását, - tanulmányoztuk kationos festékek megkötődését több kötéshelyű szupramolekuláris receptorokon, párhuzamos reakciókból álló reakció-modelleket állítottunk fel és kiszámítottuk az egyensúlyi állandókat, - meghatároztuk a fotodinamikus terápiában (PDT) potenciálisan hatóanyagként alkalmazható ftalocianinoknak a PDT-s hatás szempontjából érdekes fotofizikai/fotokémiai jellemzőit. | Photoactive compounds have been studied in solution and in supramolecular complexes by UV-VIS absorption, fluorescence and CD spectroscopy and by time-resolved laser spectroscopic experiments. The results have been interpreted with help of quantum chemical calculations. As results of the project - a new model has been created to describe the orientational relaxation of fluorescent cationic dyes, - the decay mechanism of the excited electronic states of some fluorescent probes has been clarified, - equilibrium constants characterizing the selectivity of new metal ion binding supramolecular receptors and the enantioselectivity of new chiral supramolecular receptors have been determined, - the binding of cationic dyes on supramolecular receptors with multiple binding sites has been studied, the results have been interpreted in terms of reaction models with simultaneous reactions, - the photophysical/photochemical characteristics of new phtalocyanines relevant of their application in photodynamic therapy, have been determined

Synthesis and in vitro photodynamic activity of aza-BODIPY-based photosensitizers

Aza-BODIPY dyes have recently come to attention owing to their excellent chemical and photophysical properties. In particular, their absorption and emission maxima can efficiently be shifted to the red or even to the NIR spectral region. On this basis, aza-BODIPY derivatives are widely investigated as fluorescent probes or phototherapeutic agents. Here we report the synthesis of a set of novel aza-BODIPY derivatives as potential photosensitizers for use in photodynamic therapy. Triazolyl derivatives were obtained via Cu(I)-catalyzed azide-alkyne cycloaddition as the key step. In vitro photodynamic activities of the newly synthesized compounds were evaluated on the A431 human epidermoid carcinoma cell line. Structural differences influenced the light-induced toxicity of the test compounds markedly. Compared to the initial tetraphenyl aza-BODIPY derivative, the compound bearing two hydrophilic triethylene glycol side chains showed substantial, more than 250-fold, photodynamic activity with no dark toxicity. Our newly synthesized aza-BODIPY derivative, acting in the nanomolar range, might serve as a promising candidate for the design of more active and selective photosensitizers

Fluorescence spectroscopic evaluation of the interactions of quercetin, isorhamnetin, and quercetin-3'-sulfate with different albumins

Quercetin is one of the most commonly occurring flavonoids in nature. Although, quercetin and its metabolites express negligible fluorescence, the albumin-bound form of quercetin has a strong fluorescence property. Considering the structural variance of different albumins, we hypothesized that the fluorescence of albumin complexes of quercetin and its metabolites may vary significantly. Therefore, in this study the fluorescence enhancement of quercetin and some of its major metabolites in the presence of bovine (BSA), human (HSA), porcine (PSA), and rat serum albumins (RSA) were investigated by steady-state fluorescence spectroscopy in PBS buffer (pH 7.4). Among the tested quercetin metabolites, significant fluorescence signal was shown by albumin complexes of quercetin, isorhamnetin, and quercetin-3’-sulfate, while other metabolites (tamarixetin, quercetin-3-glucuronide, and isorhamnetin-3-glucuronide) expressed negligible fluorescence. BSA was the most potent enhancer of quercetin-3’-sulfate but it showed poor effects regarding other flavonoids. The strongest enhancement of isorhamnetin was caused by HSA, while it was less effective enhancer of quercetin and quercetin-3’-sulfate. PSA showed a strong fluorescence enhancement of quercetin and quercetin-3’-sulfate but it was poorly effective regarding isorhamnetin. RSA was the most potent enhancer of quercetin but it caused only a weak enhancement of isorhamnetin and quercetin-3’-sulfate. Large changes of the pH (such as pH 5.0 and pH 10.0) almost completely abolished the fluorescence signals of the complexes. Nevertheless, slight decrease (pH 7.0) reduced and slight increase (pH 7.8) generally enhanced the fluorescence of flavonoid-albumin complexes (only exceptions were quercetin-PSA and quercetin-RSA). Complex formations were also investigated by fluorescence quenching studies. Based on our results, the formations of quercetin-BSA, quercetin-HSA, isorhamnetin-BSA, isorhamnetin-HSA, isorhamnetin-PSA, and quercetin-3’-sulfate – HSA complexes followed 1:1 stoichiometry, while the presence of a secondary binding site of flavonoids was assumed regarding other tested albumin complexes. Our study highlights that albumins can induce significantly different fluorescence enhancement of flavonoids, and even the stoichiometry of flavonoid-albumin complexes may differ

Interaction of α- and β-zearalenols with β-cyclodextrins

Zearalenone (ZEN) is a mycotoxin produced by Fusarium fungi. ZEN primarily contaminates different cereals, and exerts a strong xenoestrogenic effect in animals and humans. ZEN is a fluorescent mycotoxin, although molecular interactions and microenvironmental changes significantly modify its spectral properties. During biotransformation, ZEN is converted into α-zearalenol (α-ZOL) and β-zearalenol (β-ZOL), the toxic metabolites of ZEN, which mimick the effect of estrogen. Cyclodextrins (CDs) are host molecules, and have been studied extensively; they can form stable complexes with several mycotoxins, including ZEN. However, information is limited regarding the interactions of CDs with ZOLs. Therefore, we studied the interactions of α- and β-ZOLs with native and six chemically modified β-CDs by fluorescence spectroscopy. Fluorescence enhancement during complex formation, as well as binding constants, were determined. To understand ZOL-CD interactions better, molecular modeling studies were also carried out. Both mycotoxin derivatives formed the most stable complexes with methylated and sulfobutylated CD-derivatives; however, the CD complexes of α-ZOL were significantly stronger than those of β-ZOL. The data presented here indicate which of the chemically modified β-CDs appear more suitable as fluorescence enhancers or as potential mycotoxin binders

Validation of the Musculoskeletal Health Questionnaire in a general population sample:a cross-sectional online survey in Hungary

BACKGROUND: The Versus Arthritis Musculoskeletal Health Questionnaire (MSK-HQ) measures symptom severity and health-related quality of life (HRQoL) of people with musculoskeletal (MSK) conditions. We aimed to test the psychometric properties of the MSK-HQ among the general adult population and identify the determinants of MSK-HQ states. In addition, we aimed to explore the relationship between MSK-HQ and standard well-being measurement tools. METHODS: The translation proccess of the MSK-HQ into Hungarian followed the standard methods provided by the developer. A cross-sectional online survey was performed in Hungary involving a population normative sample (N = 2004, women: 53.1%; mean age: 48.3, SD = 16.6 years). Socio-demographic characteristics and self-reported MSK disorders were recorded. Alongside the MSK-HQ, standard measures of HRQoL (EQ-5D-5L), physical functioning (HAQ-DI) and well-being (ICECAP-A/O, WHO-5, Happiness VAS) were applied. Clinical and convergent validity were assessed by subgroup comparisons (Mann–Whitney-U and Kruskal–Wallis tests) and Spearman’s rank correlations. Internal consistency was assessed by Cronbach’s alpha. Test–retest reliability (N = 50) was evaluated by intraclass correlation coefficient (ICC). Predictors of MSK-HQ were analysed by ordinary least square multiple regressions. RESULTS: The mean MSK-HQ index score was 44.1 (SD = 9.9). MSK-HQ scores were significantly lower in subgroups with self-reported MSK disorders. Correlations were strong between MSK-HQ and EQ-5D-5L (0.788), EQ VAS (0.644) and HAQ-DI (-0.698) and moderate with the well-being measures (p < 0.05). Cronbach’s alpha was 0.924 and ICC was 0.936 (p < 0.05). Being a man, living in the capital, having higher income and education were positively associated with MSK-HQ scores. CONCLUSIONS: This is the first study to prove the validity and reliability of the MSK-HQ among the general public. The impact of socio-demographic characteristics on MSK-HQ scores deserves consideration in clinical studies. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12891-022-05716-9

Flavonoid diosmetin increases ATP levels in kidney cells and relieves ATP depleting effect of ochratoxin A

Diosmetin (DIOS) is a flavone aglycone commonly occurring in citrus species and olive leaves, in addition it is one of the active ingredients of some medications. Based on both in vitro and in vivo studies several beneficial effects are attributed to DIOS but the biochemical background of its action seems to be complex and it has not been completely explored yet. Previous investigations suggest that most of the flavonoid aglycones have negative effect on ATP synthesis in a dose dependent manner. In our study 17 flavonoids were tested and interestingly DIOS caused a significant elevation of intracellular ATP levels after 6- and 12-h incubation in MDCK kidney cells. In order to understand the mechanism of action, intracellular ATP and protein levels, ATP/ADP ratio, cell viability and ROS levels were determined after DIOS treatment. In addition, impacts of different enzyme inhibitors and effect of DIOS on isolated rat liver mitochondria were also tested. Finally, the influence of DIOS on the ATP depleting effect of the mycotoxin, ochratoxin A was also investigated. Our major conclusions are the followings: DIOS increases intracellular ATP levels both in kidney and in liver cells. Inhibition of glycolysis or citric acid cycle does not decrease the observed effect. DIOS-induced elevation of ATP levels is completely abolished by the inhibition of ATP synthase. DIOS is able to completely reverse the ATP-depleting effect of the mycotoxin, ochratoxin A. Most probably the DIOS-induced impact on ATP system does not originate from the antioxidant property of DIOS. Based on our findings DIOS may be promising agent to positively influence ATP depletion caused by some metabolic poisons