Radu Silaghi-Dumitrescu

Babeş-Bolyai University | UBB · Faculty of Chemistry and Chemical Engineering

Hemoglobin-based oxygen carriers (HBOCs) have been proposed and tested for several decades for the treatment of hemorrhage. We have previously proposed replacing hemoglobin (Hb) in HBOC with the oxygen-carrying protein hemerythrin (Hr), from marine worms, showing that Hr-based derivatives can perform at least as well or even better than Hb-based HB...

Molecular dynamics simulations were employed in order to analyze the interfacial interaction of polylactic acids with zirconia and hydroxyapatite surfaces. The interactions of polymers on five crystallographic planes were simulated. Silane coupling agents can improve the interactions between the bioceramic surfaces and the polylactic acids. The eff...

The nature of the blue color in the iodine-starch reaction is still a matter of debate. Some textbooks still invoke charge-transfer bands within a chain of neutral I2 molecules inside the hydrophobic channel defined by the interior of the amylose helical structure. However, the consensus is that the interior of the helix is not altogether hydrophob...

The oxygen carrying protein hemerythrin represents an alternative raw material to hemoglobin-based blood substitutes due to its reversible oxygen binding properties, relatively low redox reactivity and limited cytotoxicity. In order to increase the hydrodynamic volume and lower antigenicity, two site-directed variants, H82C and K92C, containing a s...

In this work, two new phenothiazinium dyes containing N-piperidinyl-carbinol auxochrome units have been designed, synthesized and investigated in vitro for ovarian cancer cell fluorescence imaging and cytotoxicity. A solvent free mechanochemical procedure is described as a greener alternative to the previously reported synthetic methodology applied...

Nitrosylcobinamide (NOCbi) is a tight complex between Co(II)-form of cobinamide, a nucleotide-free analog of cobalamin (vitamin B12), and nitric oxide (NO). Here, we report that NOCbi exhibits high resistance toward aerobic oxidation in comparison with nitrosylcobalamin. NOCbi slowly degrades in the presence of hydrogen peroxide and undergoes a mor...

The growing interest in the appearance and color of teeth has led to the emergence of a wide range of teeth whitening methods, both in dental offices and in patients’ homes. Concerns about the possible side effects or toxic effects of peroxide-based whitening gels leads to the identification of alternative whitening methods, based on natural compou...

Haptoglobin (Hp) is a protein with role in oxidative stress prevention, which it fulfills by trapping hemoglobin (Hb) dimers in a strongly-bound complex, thus reducing Hb's ability to engage in oxidative stress reactions which are greatly enhanced when the Hb tetramer falls apart into dimers. A first molecular dynamics (MD) analysis is presented he...

Aquacobalamin binds hydrogen peroxide reversibly to form a cobalt(III) hydroperoxo adduct with a 0.25 mM dissociation constant, as evidenced by UV-vis absorption spectroscopy and corroborated by NMR, Raman spectroscopy, stopped-flow UV-vis measurements, and density functional theory calculations.

The present study examined generation of hydroxyl radical (HO•) in aqueous aerobic solutions (pH 7.1) containing selenite (SeO3²⁻) and glutathione (GSH) using terephthalic acid (TA) scavenging HO• to give highly fluorescent 2-hydroxyterephthalic acid (TA-OH). The highest reaction rate and yield of TA-OH were observed in a micromolar concentration r...

The structures and energetics of the binuclear ethylenedithiolate iron carbonyls H2C2S2Fe2(CO)n (n = 8, 7, 6, 5, 4) have been studied using density functional theory. The experimental H2C2S2Fe2(CO)6 structure with the ethylenedithiolate ligand bridging the central Fe–Fe bond through both of its sulfur atoms but with an uncomplexed C=C double bond i...

The structures and energetics of species with the stoichiometries (Me2CNO)M(CO)nCp (M = Cr, Mo, W; n = 3, 2, 1; Cp = η5-C5H5) have been studied by density functional theory....

The anticancer drug vincristine, known to act by inhibiting tubulin function in human cells, is shown to affect autoxidation rates in hemoglobin – either alone or under conditions where nitrite acts as an initiator in a nitrosative stress cascade. This behavior mirrors those observed by us with four other antitubulin agents-irinotecan, docetaxel, p...

Molecular oxygen-enriched water (OxEW) is advocated in popular media as useful for various health issues, presumably due to involvement of a purported antioxidant activity and to such notions as “active oxygen.” To our knowledge, there are no explicit reports in the scientific literature where such redox reactivity would be described and explained....

p> National anthems are occasionally quoted, mostly based on anecdotal evidence or arguments, to be correlated with societal features. The present study aims to identify the pervasive topics in national anthems, and then to establish whether connections may be established between these topics and some basic societal features. Upon examination of ~2...

Hemoglobin- (Hb-) based oxygen carriers (HBOC) have for several decades been explored for treatment of hemorrhage. In our previous top-up tests, HBOC with lower in vitro prooxidant reactivity (incorporating a peroxidase or serum albumin to this end) showed a measurable but small improvement of oxidative stress-related parameters. Here, such HBOCs a...

Site-directed spin labeling and EPR characterization (continuous wave as well as DEER) of two blood substitute candidates is described for the first time: glutaraldehyde-polymerized bovine hemoglobin and the related hemoglobin-albumin copolymer. In vitro, with two different types of cell cultures, these spin-labeled candidates are relatively stable...

Excess ascorbate (as expected in intravenous treatment proposed for COVID-19 management, for example) oxidizes and/or degrades hemoglobin and albumin, as evidenced by UV-vis spectroscopy, gel electrophoresis, and mass spectrometry. It also degrades hemoglobin in intact blood or in isolated erythrocytes. The survival rates and metabolic activities o...

Glutaraldehyde (GA) is used as biocide in hospitals. Recent public investigations on the chemical composition of biocides used in Romania have in some cases found GA, as a key ingredient, to be apparently diluted. However, these data did not explicitly consider the complex chemical equilibria inherent to GA. An investigation of experimental and the...

Classical molecular mechanics and quantum mechanical dynamics calculations of iron and cobalt hydroperoxo adducts of bleomycin with deoxyribonucleic acid (DNA) yield structures in reasonable agreement with the experimentally-known Co structures. The hydroxyl (OH) group of the metal-bound hydroperoxide is predicted to reside very close to a deoxyrib...

Yellow laccases lack the typical blue type 1 Cu absorption band around 600 nm; however, multi-copper oxidases with laccase properties have been reported. We provide the first evidence that the yellow laccase isolated from Sclerotinia sclerotiorum is obtained from a blue form by covalent, but nevertheless reversible modification with a phenolic prod...

The rhenadicarbaborane carbonyl nitrosyls (C2B n -3H n -1)Re(CO)2(NO), (n = 8 to 12), of interest in drug delivery agents based on the experimentally known C2B9H11Re(CO)2(NO) and related species, have been investigated by density functional theory. The lowest energy structures of these rhenadicarbaboranes are all found to have central ReC2B n -3 mo...

Sulfite reductase (SiR) contains in the active site a unique assembly of siroheme and a [4Fe4S] cluster, linked by a cysteine residue. Siroheme is a doubly reduced variant of heme that is not used for the catalytic function in any other enzyme. We have used non-equilibrium Green’s function methods coupled with density functional theory computations...

Background: Natural extracts with beneficial biological activities are nowadays of high interest, in various treatment or prophylaxis. Hypericum capitatum has been known for its curative effects for centuries and its extracts have become of interest due to their distinct activity among other Hypericaceae members. In this study, further light is ai...

Reduction of dietary selenite (SeO3H⁻, SeO3H2) is an important process in vivo, which predominantly involves glutathione (GSH). Although the reaction between selenite and thiols has been studied extensively, its mechanism and the identification of products remain controversial. Herein, we present kinetic, spectroscopic and in silico data on the fir...

The aim of the present study was to establish the best experimental conditions that lead to the extracts richest in polyphenolic compounds obtained from pomace and canes of Vitis vinifera. In this regard, a D-Optimal design of experiments (DoE) method was applied to investigate the extraction process parameters from each of three materials: red pom...

The experimentally known cobalt ethylenedithiolate complex CpCoS2C2H2 as well as its rhodium and iridium analogues are aromatic systems that can function as pentahapto six-electron donor metallodithiolene ligands by binding through...

Starting from 4-amino-1-(tert-butoxycarbonyl)piperidine (Boc-PD-NH2), we report the synthesis of three novel meta-tri- and dimeric tetravalent N-substituted melamines with piperidin-4-yl groups. These compounds were used as central building-blocks and successfully incorporated into three new G-2 melamine dendrimers containing 4-(n-octyloxy)aniline...

Hemoglobin’s redox reactivity is affected by anticancer drugs of the antitubulin class. Direct binding of these drugs to hemoglobin, with biomedically-relevant affinities, is demonstrated. While this interaction is mostly allosteric, in the case of docetaxel a direct redox reaction is also observed – correlating well with structural differences bet...

Hemoglobin in its ferryl form oxidizes hydrogen sulfide and is transformed to sulfhemoglobin, where the sulfur is inserted covalently at the heme edge. Shown here is evidence that—as previously proposed by others—this process involves oxidation of hydrogen sulfide to a sulfanyl radical detectable by spin-trapping in electron paramagnetic resonance...

The chemical composition, antiradical and antimicrobial activity of cold-pressed edible oils from nutty fruits (almond and walnut) and oils from poppy seed and wheat germ from Macedonia were studied. Regarding the fatty acid composition, the highest level of oleic acid was determined in almond oil (67.6 ± 0.02%) whereas poppy seed oil was the riche...

The reaction of Mn(CO)5Br with sodium ethylenedithiolate was reported in 1968 to give a dark red binuclear H2C2S2Mn2(CO)6 complex possessing the unusual property of complexing reversibly with ammonia to give a yellow H2C2S2Mn2(CO)6·NH3 adduct. In order to provide some insight into the nature of this adduct, density functional studies were performed...

The present study describes the first example of the stoichiometric and catalytic oxidation of flavanone by synthetic nonheme oxoiron(IV), and their precursor iron(II) complexes with m-CPBA as terminal oxidant. These...

Despite a recent increase in interest towards phytoglobins and their importance in plants, much is still unknown regarding their biochemical/biophysical properties and physiological roles. The present study presents data on three recombinant Arabidopsis phytoglobins in terms of their UV-vis and Raman spectroscopic characteristics, redox state contr...

Sulfite reductase (SiR) catalyzes a six electron and six proton reduction of sulfite to sulfide. Similarly to the cytochrome P450 (cytP450) family, the active site in SiR contains a (partially reduced) heme bound axially to a cysteinate ligand—though with an extra Fe4S4 cluster. Fe(III)SO²⁻, Fe(III)SOH⁻, and Fe(III)SO(H2) intermediates have been...

With the largest number of casualties in human history, unprecedented planetary scale and documented cruelty, the two World Wars have marked the XXth century as a time for extreme violence. Nevertheless, the casualties documented for wars across the past ~2000 years equate to percentages of population in no way larger in the XXth century. Arguably,...

The biological properties and main phenolic compounds of the O. vulgare L. ssp. vulgare extract are described in the present paper. The polyphenolic compounds were analyzed by chromatographic and spectrophotometric techniques. The antioxidant potential was evaluated using several methods: CUPRAC (cupric ion reducing antioxidant capacity), FRAP (fer...

Background Although Galanthus nivalis L. (snowdrop) is known for the galanthamine content, used in the treatment of Alzheimer disease, the polyphenolic compounds of Amaryllidaceae species are less studied. Proper understanding of the polyphenolics in these extracts and of their antioxidant and antimicrobial properties may allow a reconsideration of...

Galium verum is a well-known medicinal plant which is used in various pathologies. G. verum extracts are characterized here using chromatography, where among the rich pool of phenolic acids of flavonoids two known anti-stress modulators, chlorogenic acid and rutin are identified in high quantities. Additionally, the extracts are characterized using...

HPTLC images of the silica gel plates, 60F254 developed with toluene: Acetone: Formic acid, 9:9:2 (v/v/v) as mobile phase. Derivatized with NP/PEG (A.) visible (B.) UV 254 nm (C.) UV 366 nm. Bands: 1 –ferulic acid, 2 –galic acid, 3 –chlorogenic acid, 4—quercetin, 5—rutin, 6—kaempferol, 7 –G.verum extract. (DOCX)

Hemoglobin has previously been shown to display ascorbate peroxidase and urate peroxidase activity, with measurable Michaelis-Menten parameters that reveal a particularly low Km for ascorbate as well as for urate - lower than the respective in vivo concentrations of these antioxidants in blood. Also, direct detection of a hemoglobin-ascorbate inter...

Reported here is a comparative analysis of the milk from three representative breeds of dairy cows from Romania – Maramures Brown (Brună de Maramureş), Romanian Spotted (Bălțata Românească) and Black Spotted Romanian (Bălțata cu Negru Românească) - in terms of SDS-PAGE analysis of the protein distribution, total contents of protein, lipids, lactose...

The bioactive compounds and “in vitro” antioxidant activity measured by three antioxidant assays of some traditional and non-traditional cold-pressed edible oils from Macedonia were object of this study. The fatty acid composition showed dominance of monounsaturated oleic acid in “sweet” and “bitter” apricot kernel oils with percentages of 66.7 ± 0...

The autocatalytic reaction between nitrite and the oxy form of globins involves free radicals. For myoglobin (Mb), an initial binding of nitrite to the iron-coordinated oxygen molecule was proposed; the resulting ferrous-peroxynitrate species was not detected, but its decay product, the high-valent ferryl form, was demonstrated in stopped-flow expe...

A recent expansion of anticorruption campaigns in Romania finds such media coverage, that parts of the society appear to be oversaturated. Together with doubts raised on the legitimacy of several of the higher-profile cases put forth by the prosecutors, this has led to an ironic public proposal that prison terms be compulsory for all citizens as a...

Foreign occupation in Eastern Europe during and after 1939 has entailed widespread administrative reorganizations and replacement of previously-established national elites by arbitrary leadership exercising abusive force and dictatorship, at odds with self-asserted “popular power” and “people’s democracy”. One may argue that the mechanisms whereby...

Ascorbate as well as other antioxidants (urate, caffeic acid and bovine albumin) are shown to alleviate oxidative damage (hemoglobin oxidation, cell lysis) effected by cisplatin on red blood cells. While such reactivity is visible at physiological ascorbate levels, at concentrations of 1 mM and above ascorbate alone induces oxidation of hemoglobin....

We have previously demonstrated that derivatization of hemoglobin with periodate-modified sugar derivatives incurs increases in the pro-oxidant reactivity and, also, that serum bovine serum albumin can resolve this problem entirely. Here, we described a new polymer based on hemoglobin and another oxygen-containing compound, alginate. The rate of au...

Putative elements of secondary, tertiary and quaternary structure were examined for polylactic acid chains, attempting a parallel with secondary structure elements known from protein biology and also attempting an estimate, based on accurate atomic-level calculations, of interaction energies between polylactic acid chains. Spectroscopic parameters...

Reported here is a density functional theory study on the ability of Ni-substituted iron-dependent cysteine dioxygenase (CDO) to catalyze the oxidation of cysteine to cysteine sulfinic acid. The first steps of the commonly accepted mechanism for CDO, the O2 activation mechanism, suggests the binding of O2 to the metal ion (where redox isomerism tak...

Rhodotorula mucilaginosa was isolated from a patient with onychomycosis, and identification was confirmed by morphological and cultural characteristics as well as by DNA molecular analysis. Antifungal agents naftifine (10 mg/mL, active substance in Exoderil) and bifonazole (10 mg/mL, active substance in Canespor) were tested in different concentrat...

The tetracapped tetrahedral Ru4S4X4z structures (X = Cl, CN, SCH3; z = 0 to -4) are proposed as cubanoid low-spin models for the Fe4S4 structural units in metalloenzymes. Density functional theory indicates the Ru4S4X4²⁻ dianions to have closed shell configurations. A bonding model with 4 external RuX bonds, 12 RuS bonds along the edges of an Ru4S4...

The present study reports findings regarding the contrast between H2S interaction with bovine hemoglobin (Hb) and horse heart myoglobin (Mb), in terms of binding and dissociation kinetics, affinities, and mechanism. At pH9.5, oxidation of ferric-sulfide adducts in presence of no free sulfide, using hexachloroiridate as oxidant is examined using sto...

We have previously proposed the annelid-derived protein, hemerythrin, as a viable replacement for hemoglobin in the synthesis of semi-synthetic oxygen carriers ("blood substitutes"). Here, we report the first in vivo tests for potential hemerythrin-based oxygen carriers (HrBOC), using a battery of experiments involving Wistar rats and previously te...

Bromination of (AsPh2)2S leads to cleavage of the sulfide bridge to give AsPh2Br when 1mol of bromine is used but with 2mols the product is the polybromide, [AsPh2Br2]2[Br8], containing the previously unknown [AsPh2Br2]⁺ cation and a rare [(Br3)⁻...(Br2)...(Br3)⁻] ensemble whose short (yet not covalent) Br2...Br3 contacts have previously supported...

The kinetics of reactions of cobalamin (II) and cobinamide (II) with sulfur dioxide was studied by UV-visible (UV-vis) spectroscopy. Reaction results in oxidation of Co(II) center and involves two aquated SO2 moieties. The final product is suggested to be complex Co(III)-S2O 4(•-) . The absence of corrin ring modifications during the reactions was...

The reaction between tetramethylthiourea (TMTU) and hydrogen peroxide was studied by UV–VIS spectroscopy, ESI mass spectrometry, ¹H NMR, cyclic voltammetry and surface-enhanced Raman scattering. We found that the reaction includes two consecutive steps, that is, (i) an oxidation of TMTU to TMTU monoxide (TMTMO) and (ii) further oxidation of TMTU mo...