Improved voltammetric methodology for chromium redox speciation in estuarine waters

Chromium is a toxic element naturally present in natural waters whose chemical speciation regulates its cycling, mobility and bioavailability. We present here: 1- an improved analytical method for chromium speciation (Cr(VI) vs Cr(III)) in estuarine samples by catalytic adsorptive cathodic stripping voltammetric (cat-AdCSV) and 2- a study highlighting a significant change of redox speciation during summer and winter. Initial measurements first revealed that surface-active substances (SAS) present in estuarine samples strongly influenced the analytical determination of Cr by partially masking the Cr peak through an increase of the background current. We found that the application of a low negative accumulation potential (−1.65 V) resulted in much better voltammograms compared to those obtained using the usual accumulation potential of −1.0 V. Using humic acid (HA) as a model SAS of natural origin, we show that this negative potential clearly prevents adsorption of SAS on the Hg-electrode surface, which in turns benefits the adsorption of the in-situ formed Cr(III)-DTPA complex and the resulting signal. The optimised method was applied to determine chromium redox speciation and distribution along the 23 km long salinity gradient, well oxygenated, Krka River estuary (Croatia). Cr(VI) was found to be the dominant redox species in both summer and winter, with Cr(III) contribution being lower in summer (up to ∼30%, average of ∼5%) than in winter (up to ∼50%, average of ∼30%). In summer, lower concentrations of Cr(VI) were found in the freshwater end-member (2.5 nM) than in the seawater end-member (4–5 nM), while the opposite trend was found in winter. Hexavalent chromium exhibited a non-conservative behaviour along the salinity gradient for both seasons. Chromium predominantly exists in dissolved phase, and contribution of particles reactive Cr(III) was minor

Dipyridinium 2,2′-dithiodinicotinate

The dianion of the title salt, 2C5H6N+·C12H6N2O4S22−, lies on a special position of 2 site symmetry that relates one thionicotinate part to the other, and the dihedral angle between the niotinate planes is 89.2 (2)°. The pyridinium cations are hydrogen bonded to the carboxylate group by way of N—H...O links

Novel semicarbazides and ureas of primaquine with bulky aryl or hydroxyalkyl substituents: Synthesis, cytostatic and antioxidative activity

Novel primaquine semicarbazides 7a-l and ureas 9a-g with modified benzhydryl, trityl, phenyl or hydroxyalkyl substituents were prepared and evaluated for cytostatic and antioxidative activities. Two synthetic approaches for preparation of the title semicarbazides were applied, both having certain advantages. In the first approach, the products grew from the semicarbazide side and the primaquine residue entered the molecule the last. In the second approach, semicarbazide grew from the primaquine side. This method was more convenient for synthesis of a series of semicarbazides: various products could be obtained from the same precursor N-(4-((6-methoxyquinolin-8-yl)amino)pentyl)hydrazinecarbox-amide (10). Primaquine ureas 9a-f were prepared from primaquine benzotriazolide 8 and corresponding amines and urea 9g directly from primaquine and 4-chloro-3-(fluoromethyl)phenyl isocyanate. All primaquine semicarbazide derivatives showed either prominent cytostatic activity towards all the tested cell lines (benzhydryl or trityl derivatives 7a-e) or high selectivity towards MCF-7 cells (hydroxyalkyl derivatives 7h-l), with IC50 values in the low micromolar range. The highest selectivity exerted symmetric bisprimaquine derivative 7f, with an IC50 0.2 μM against MCF-7 cells and practically no activity against other seven tested cancer cell lines. Urea derivatives 9a-f were generally less active than their semicarbazide analogues, but still selective towards MCF-7 cells. Urea 9g with the similar structure to cytostatic drug sorafenib, was the most active urea derivative. Semicarbazides 7g and 10 showed the best antioxidative activity as measured by DPPH (64% at 20 min and 90% at 60 min), while urea derivatives 9a-g, especially 9d, and semicarbazides 7a-g with lipophilic substituents exerted better LP antioxidant activity. Both semicarbazides and ureas with methoxy or chloro benzhydryl substituents and high Clog P values showed significant LOX inhibition.publisher: Elsevier articletitle: Novel semicarbazides and ureas of primaquine with bulky aryl or hydroxyalkyl substituents: Synthesis, cytostatic and antioxidative activity journaltitle: European Journal of Medicinal Chemistry articlelink: http://dx.doi.org/10.1016/j.ejmech.2014.09.013 content_type: article copyright: Copyright © 2014 Elsevier Masson SAS. All rights reserved.status: publishe

Dose imbalance of DYRK1A kinase causes systemic progeroid status in Down syndrome by increasing the un-repaired DNA damage and reducing LaminB1 levels.

BACKGROUND: People with Down syndrome (DS) show clinical signs of accelerated ageing. Causative mechanisms remain unknown and hypotheses range from the (essentially untreatable) amplified-chromosomal-instability explanation, to potential actions of individual supernumerary chromosome-21 genes. The latter explanation could open a route to therapeutic amelioration if the specific over-acting genes could be identified and their action toned-down. METHODS: Biological age was estimated through patterns of sugar molecules attached to plasma immunoglobulin-G (IgG-glycans, an established "biological-ageing-clock") in n = 246 individuals with DS from three European populations, clinically characterised for the presence of co-morbidities, and compared to n = 256 age-, sex- and demography-matched healthy controls. Isogenic human induced pluripotent stem cell (hiPSCs) models of full and partial trisomy-21 with CRISPR-Cas9 gene editing and two kinase inhibitors were studied prior and after differentiation to cerebral organoids. FINDINGS: Biological age in adults with DS is (on average) 18.4-19.1 years older than in chronological-age-matched controls independent of co-morbidities, and this shift remains constant throughout lifespan. Changes are detectable from early childhood, and do not require a supernumerary chromosome, but are seen in segmental duplication of only 31 genes, along with increased DNA damage and decreased levels of LaminB1 in nucleated blood cells. We demonstrate that these cell-autonomous phenotypes can be gene-dose-modelled and pharmacologically corrected in hiPSCs and derived cerebral organoids. Using isogenic hiPSC models we show that chromosome-21 gene DYRK1A overdose is sufficient and necessary to cause excess unrepaired DNA damage. INTERPRETATION: Explanation of hitherto observed accelerated ageing in DS as a developmental progeroid syndrome driven by DYRK1A overdose provides a target for early pharmacological preventative intervention strategies. FUNDING: Main funding came from the "Research Cooperability" Program of the Croatian Science Foundation funded by the European Union from the European Social Fund under the Operational Programme Efficient Human Resources 2014-2020, Project PZS-2019-02-4277, and the Wellcome Trust Grants 098330/Z/12/Z and 217199/Z/19/Z (UK). All other funding is described in details in the "Acknowledgements"

Notable Radiophysicists and Radiochemists in Croatia by 1945

U ovome preglednom radu dan je uvid u život i rad doajena znanosti o zračenju i zaštite od zračenja u Hrvatskoj do 1945. godine. Efektivni počeci znanosti o zračenju, pa tako i zaštite od zračenja na području Hrvatske sežu čak do kraja 19. stoljeća. Fizičari i kemičari bili su među prvima mogućim žrtvama izloženosti ionizirajućem zračenju, pa su tako i bili prvi koji su upozoravali na štetne učinke radijacije na žive organizme. Pretraživanje dostupnih arhiva i poznate literature nije samo rasvijetlilo život i rad doajena znanosti o zračenju već je omogućilo sistematičan uvid u do sada nepoznate detalje važne za povijest i razvoj znanosti o zračenju, zaštite od zračenja, kao i o medicinskoj fi zici. Sve to pokazuje da Hrvatska od samoga početka ne samo da slijedi najsuvremenije znanstvene spoznaje iz tih područja, već i njima aktivno pridonosi.Physicists and chemists were among the first potential victims of occupational exposure to ionising radiation and they were also the first to warn about the harmful effects of radiation on living organisms. This review presents the work of the first notable scientists in the field of radiation science in Croatia from the discovery of radiation (Henry Becquerel in 1896) to 1945. The beginning of radiation science and radiation protection in Croatia can be traced to the end of the 19th century. Our research of the archived material and literature not only gave a deeper insight to the life and work of some of these notable scientists, but also gave a glimpse of previously unknown facts and details important for the history and development of radiation science, radiation protection, as well as medical physics. Our research has shown that Croatian scientists not only kept pace with contemporary scientific knowledge but also made notable contributions from the very beginning