Thermodynamics of complexation of alkaline-earth metal cations by a fluorescent phenathridine-based calix[4]arene derivate

Sustavno je istraženo kompleksiranje kationa zemnoalkalijskih metala s derivatom kaliks[4]arena koji na donjem obodu posjeduje dvije fluorescentne fenantridinske podjedinice i dva supstituenta s tercijarnim amidnim skupinama, koji zajedno čine efikasno vezno mjesto za katione. U svrhu detaljnijeg proučavanja utjecaja otapala na ravnoteže procesa kompleksiranja, provedena su istraživanja reakcija u acetonitrilu, metanolu i etanolu. Kompleksiranje je istraženo spektrofotometrijskim, fluorimetrijskim te izotermnim mikrokalorimetrijskim izravnim i kompeticijskim titracijama. Određene su konstante stabilnosti nastalih kompleksa (i iz njih izračunane odgovarajuće standardne reakcijske Gibbsove energije) te standardne reakcijske entalpije i entropije. Proučavani kaliksaren pokazuje iznimno velik afinitet prema zemnoalkalijskim kationima u acetonitrilu, daleko manji u etanolu te još manji u metanolu. U acetonitrilu termodinamički je najstabilniji kompleks s Ca2+, dok u metanolu i etanolu najveća konstanta stabilnosti odgovara kompleksu sa Sr2+. Razlike u afinitetima za vezanje kationa uglavnom su posljedica različite solvatacije vrsta prisutnih u otopini i kompatibilnosti veličine kationa i veznog mjesta liganda. U acetonitrilu su u svim slučajevima i entalpijski i entropijski doprinos standardnoj reakcijskoj Gibbsovoj energiji povoljni, dok su u metanolu i etanolu reakcije kompleksiranja endotermne i entropijski kontrolirane. Istraživani ligand pokazao se vrlo efikasnim i osjetljivim fluorescentnim receptorom za Ca2+ i Sr2+ u acetonitrilu.The complexation of alkaline-earth metal cations with tertiary-amide lower-rim fluorescent calix[4]arene derivative comprising two phenanthridine moieties was studied by means of spectrophotometric, fluorimetric, and microcalorimetric direct and competitive titrations. In order to investigate the solvent effect on cation-binding processes, the complexation reactions were studied in acetonitrile, methanol, and ethanol, whereby the complex stability constants (and derived standard reaction Gibbs energies) as well as standard reaction enthalpies and entropies of complexation reactions were determined. The investigated calixarene exhibited high affinity towards alkaline-earth metal cations in acetonitrile, with low selectivity and peak affinity corresponding to Ca2+, whereas the complex stabilities were significantly lower in ethanol and methanol, in which the affinity for Sr2+ was highest. The differences in cation-binding abilities were a consequence of the differences in solvation of the species present in solution as well in compatibility of the cation and binding-site sizes. The extensive solvent effect could be, at least partially, rationalized by much more favourable cation solvation in methanol and ethanol, as compared to acetonitrile. The binding reactions were enthalpically controlled in acetonitrile, as opposed to methanol and ethanol in which the reactions were endothermic and entropically driven. The investigated ligand was proven to be very effective and rather sensitive fluorescent receptor for Ca2+ and Sr2+ in acetonitrile

Utjecaj otapala na kinetiku kemijskih reakcija

Opis kinetike reakcija u otopini znatno je složeniji od reakcija u plinskoj fazi. Razlog tome je značajan broj interakcija sudionika reakcije s molekulama otapala čiji je kvantitativan opis netrivijalan. Za razmatranje kinetike reakcija u otopini je, dakle, za razliku od plinske faze, potrebno uključiti dodatne varijable vezane uz otapalo. Osim toga, interpretacija dobivenih eksperimentalnih podataka korištenjem jednostavnih kinetičkih modela daje isključivo kvalitativnu sliku o promatranom sustavu, zbog čega je za kvantitativniji opis potrebno koristiti znatno složenije modele. Osim uobičajenih varijabli koje utječu na kinetiku reakcije, kao što je primjerice temperatura, otapalo i njegove karakteristike također treba uzeti u obzir. Budući da promjena otapala nerijetko uzrokuje promjenu brzine, mehanizma i ishoda kemijske reakcije, ono je važan faktor u njezinu „usmjeravanju“. Iz tog je razloga odabir otapala izrazito važan u planiranju sinteze spojeva. Koristeći saznanja iz osnova kemijske kinetike i ponašanja tvari u otopinama moguće je na temelju pretpostavljenog mehanizma predvidjeti svojstva otapala koja bi pogodovala željenom ishodu reakcije, bilo u kontekstu brzine, prinosa, selektivnosti ili jednostavnosti provođenja i obrade reakcijske smjese. U ovom radu bit će ukratko opisana načela interakcija u otopini potrebna za daljnji opis utjecaja otapala na kinetiku reakcija. Utjecaj otapala bit će razmotren za slučaj aktivacijski kontroliranih reakcija na temelju teorije aktiviranog kompleksa, odnosno za slučaj difuzijski kontroliranih reakcija na temelju teorije sudara. Odabrani primjeri bit će dani na kraju rada kako bi pružali uvid u važnost odabira otapala za reakcije u otopini, ali i važnost prisustva malih količina otapala kod mehanokemijskih reakcija

Evaluating of some quality parameters of different apricot cultivars using HPLC method

High performance liquid chromatography (HPLC) was used for separation, identification and quantification of sugars, sugar alcohol sorbitol and non-volatile acid content in puree of 15 apricot cultivars (Prunus armeniaca L.). Sugar analyses included sucrose, glucose, fructose, xylose and sorbitol. The main organic acids characterizing apricot puree are malic, citric and fumaric acid. Variation in the content of theanalyzed compounds mentioned and also in the content of soluble solids (SS), titratable acids and pH value was found among the cultivars. Sensory evaluation showed that the content of individual organic acids and sugars as well as their relations could be crucial in forming the taste.Knowledge of the qualitative and quantitative composition of acids and sugars in apricot fruits may prove to be a powerful tool in evaluating fruit maturity and quality

Polyphenolic content and antioxidant capacity in fruits of plum (prunus domestica l.) Cultivars "valjevka" and "mildora" as influenced by air drying

Polyphenolic content and antioxidant capacity of freshly harvested plums cvs. "Valjevka" and "Mildora," and changes caused by drying were analyzed. Plum drying at 90C resulted in significant changes in anthocyanins, flavonoids and phenolics content, and antioxidant capacity in both cultivars examined. Statistical analysis showed that antioxidant capacity of both fresh plums and prunes of "Valjevka" and "Mildora" is strongly influenced by the phenolic constituents of the fruit. The major phenolic compound in fresh plums and prunes is neochlorogenic acid, followed by caffeic acid and chlorogenic acid. After drying, a significant decrease in neochlorogenic acid and an increase in caffeic acid was observed, while chlorogenic acid content decreased in prunes of "Valjevka," and increased in prunes of "Mildora." Rutin and protocatechuic acid contents were slightly decreased after drying, while gallic acid content was dramatically increased. A complete degradation of cyanidin was induced by drying

Habitat and forage associations of a naturally colonising insect pollinator, the Tree Bumblebee Bombus hypnorum

Bumblebees (Bombus species) are major pollinators of commercial crops and wildflowers but factors affecting their abundance, including causes of recent population declines, remain unclear. Investigating the ecology of species with expanding ranges provides a potentially powerful means of elucidating these factors. Such species may also bring novel pollination services to their new ranges. We therefore investigated landscape-scale habitat use and foraging preferences of the Tree Bumblebee, B. hypnorum, a recent natural colonist that has rapidly expanded its range in the UK over the past decade. Counts of B. hypnorum and six other Bombus species were made in March-June 2012 within a mixed landscape in south-eastern Norfolk, UK. The extent of different landscape elements around each transect was quantified at three scales (250 m, 500 m and 1500 m). We then identified the landscape elements that best predicted the density of B. hypnorum and other Bombus species. At the best fitting scale (250 m), B. hypnorum density was significantly positively associated with extent of both urban and woodland cover and significantly negatively associated with extent of oilseed rape cover. This combination of landscape predictors was unique to B. hypnorum. Urban and woodland cover were associated with B. hypnorum density at three and two, respectively, of the three scales studied. Relative to other Bombus species, B. hypnorum exhibited a significantly higher foraging preference for two flowering trees, Crataegus monogyna and Prunus spinosa, and significantly lower preferences for Brassica napus, Glechoma hederacea and Lamium album. Our study provides novel, quantitative support for an association of B. hypnorum with urban and woodland landscape elements. Range expansion in B. hypnorum appears to depend, on exploitation of widespread habitats underutilised by native Bombus species, suggesting B. hypnorum will readily co-exist with these species. These findings suggest that management could target bumblebee species with distinctive habitat requirements to help maintain pollination service

Calpeptin is a potent cathepsin inhibitor and drug candidate for SARS-CoV-2 infections

Several drug screening campaigns identified Calpeptin as a drug candidate against SARS-CoV-2. Initially reported to target the viral main protease (Mpro), its moderate activity in Mpro inhibition assays hints at a second target. Indeed, we show that Calpeptin is an extremely potent cysteine cathepsin inhibitor, a finding additionally supported by X-ray crystallography. Cell infection assays proved Calpeptin’s efficacy against SARS-CoV-2. Treatment of SARS-CoV-2-infected Golden Syrian hamsters with sulfonated Calpeptin at a dose of 1 mg/kg body weight reduces the viral load in the trachea. Despite a higher risk of side effects, an intrinsic advantage in targeting host proteins is their mutational stability in contrast to highly mutable viral targets. Here we show that the inhibition of cathepsins, a protein family of the host organism, by calpeptin is a promising approach for the treatment of SARS-CoV-2 and potentially other viral infections

Massive X-ray screening reveals two allosteric drug binding sites of SARS-CoV-2 main protease

The coronavirus disease (COVID-19) caused by SARS-CoV-2 is creating tremendous health problems and economical challenges for mankind. To date, no effective drug is available to directly treat the disease and prevent virus spreading. In a search for a drug against COVID-19, we have performed a massive X-ray crystallographic screen of repurposing drug libraries containing 5953 individual compounds against the SARS-CoV-2 main protease (Mpro), which is a potent drug target as it is essential for the virus replication. In contrast to commonly applied X-ray fragment screening experiments with molecules of low complexity, our screen tested already approved drugs and drugs in clinical trials. From the three-dimensional protein structures, we identified 37 compounds binding to Mpro. In subsequent cell-based viral reduction assays, one peptidomimetic and five non-peptidic compounds showed antiviral activity at non-toxic concentrations. Interestingly, two compounds bind outside the active site to the native dimer interface in close proximity to the S1 binding pocket. Another compound binds in a cleft between the catalytic and dimerization domain of Mpro. Neither binding site is related to the enzymatic active site and both represent attractive targets for drug development against SARS-CoV-2. This X-ray screening approach thus has the potential to help deliver an approved drug on an accelerated time-scale for this and future pandemics