Davor Šakić

University of Zagreb Faculty of Pharmacy and Biochemistry · Deparment of Analytical Chemistry

Proučavanje procesa stereoizomerizacije od iznimne je važnosti u farmaceutskoj kemiji i biomedicini. Različiti izomeri mogu pokazivati značajne razlike u interakciji s biološkim makromolekulama, što može dovesti do razlika i u njihovim farmakokinetičkim i farmakodinamičkim svojstvima te, u konačnici, u terapijskim i neželjenim učincima. Iako postoj...

A series of N ⁶ -substituted adenine–ferrocene conjugates was prepared and the reaction mechanism underlying the synthesis was explored. The S N 2-like reaction between ferrocenoyl chloride and adenine anions is a regioselective process in which the product ratio ( N 7/ N 9-ferrocenoyl isomers) is governed by the steric property of the substituent...

Hofmann-Löffler-Freytagova reakcija otkrivena je krajem 19. stoljeća, a munjeviti razvoj događa se posljednjih 20 godina. Primjenjuje se za stvaranje C−N veze na nesupstituiranim C−H pozicijama te za uvođenje pirolidinskih i piperidinskih prstenova na ekološki prihvatljiv način, bez upotrebe skupih metalnih katalizatora i uz vrlo učinkovite sinteze...

The inner filter effect (IFE) hinders fluorescence measurements, limiting linear dependence of fluorescence signals to low sample concentrations. Modern microplate readers allow movement of the optical element in the vertical axis, changing the relative position of the focus and thus the sample geometry. The proposed Z-position IFE correction metho...

Low-pressure pH gradient ion exchange separation provides a fast, simple and cost-effective method for preparative purification of native and desialylated apo-transferrin. The method enables easy monitoring of the extent of the desialylation reaction and also the efficient separation and purification of protein fractions after desialylation. The N-...

The Hofmann-Löffler-Freytag (HLF) reaction can be successfully used to synthesize saturated heterocyclic nitrogen-containing nature-derived pharmaceuticals such as nicotine and its derivatives. In this study the rate-determining hydrogen atom transfer (HAT) step in nicotine synthesis has been analyzed using quantum chemical methods. Through quantif...

In the reaction of purines with ferrocenoyl chloride in dimethylformamide (DMF), a regioselective acylation occurred. The two products have been isolated and, according to detailed NMR analysis, identified as N7- and N9-ferrocenoylated isomers. In more polar solvent, e.g. in dimethylsulfoxide (DMSO), the two isomers interconvert to each other. The...

Thiol-modified ferrocenes on gold have been archetypical model systems for many fundamental charge transfer and other studies, since both thiol-gold and ferrocene redox chemistry are considered to be well-understood. Thus unexpectedly, we found that for a representative of a new class of flexibly linked bis-ferrocenyl compounds, namely, 1-10-bis(1-...

Solvent effects on the absorption and fluorescence spectra of Zaleplon, a nonbenzodiazepine sedative/hypnotic drug that is mainly used for the short term treatment of insomnia, were investigated in 18 different solvents with diverse polarities. Dipole moments of the ground and excited state (μg and μe) were determined by Lippert–Mataga, Bakhshiev,...

The tranquilizer and hypnotic drug oxazepam undergoes the racemization process in aqueous medium, which is relevant for its pharmacological profile. The experimental barrier value (ΔG ‡298 ≈ 91 kJ/mol) was determined...

What happens to drugs in the chlorinating environment? Degradation products may vary in pharmacological profiles and in ecotoxicity potentials compared to the parent compound. This study combines synthesis, NMR spectroscopy, quantum chemical calculations, and toxicity experiments on Daphnia magna to investigate chemical fate of antineoplastic drug...

Supplemental information for the short paper entitled Mediated spectroelectrochemical determination of holo-transferrin reduction potential using a flow cell with disposable screen-printed indium-tin oxide electrode (https://doi.org/10.1016/j.elecom.2017.09.016). Details on the calculation of the holo-transferrin reduction potential and the electr...

A convenient spectroelectrochemical method for the determination of holo-transferrin reduction potential is described. All materials and accessories are commercially available and the results are in agreement with previous reports that required custom-built hardware. The method requires minimal preparation with simple sample handling, small solutio...

The synthesis of 1,1′-bis(thymine)ferrocene nucleoside is reported. This nucleoside was obtained in a two-step synthetic methodology including a Michael addition reaction of 1,1′-bis(3-chloropropionyl)ferrocene with thymine to afford the bis(thymine) adduct in 44 % yield. In the second step, the two prochiral carbonyl functionalities in the Michael...

Organometallic derivatives of nucleobases are characterized by distinctive biological and electrochemical properties. In this work, reduction potentials of ferrocenoyl-substituted nucleobases (uracil, 5-fluorouracil, and thymine) were measured by cyclic voltammetry and calculated by using density functional methods. Both experimental (281– 296 mV)...

The antiepileptic drug carbamazepine (CBZ) is one of the most persistent pharmaceuticals in the environment. Its chemical fate is influenced by the type of wastewater treatment. This study sets out to determine the degradation mechanism and products in the reaction between CBZ and hypochlorous acid (HOCl), which is the main chlorinating species in...

The stability of N‐centered radicals and radical cations of potential relevance in C–H amidation reactions has been quantified using highly accurate theoretical methods. Combination with available C–H bond energies for substrate fragments allows for the prediction of reaction enthalpies in 1,5‐hydrogen atom transfer (HAT) steps frequently encounter...

The front cover picture, provided by Davor Šakić and Hendrik Zipse, illustrates the utility of C–H and N–H bond dissociation energy (BDE) data for the rationalization and design of C–H amination reactions. Examples include those from classical Hofmann-Löffler-Freytag reactions as well as more current iodine(I)/iodine(III) catalysis schemes. This ty...

Flavonoids are ubiquitous plant metabolites that interfere with different biological processes in the human organism. After absorption they bind to human serum albumin (HSA), the most abundant carrier protein in the blood which also binds various hormones and drugs. Binding of flavonoids to HSA may impact their distribution, influencing the active...

The reactions of hypochlorous acid (HOCl) with ammonia, (di)methylamine, and heterocyclic amines have been studied computationally using double-hybrid DFT methods (B2PLYP-D and BK-PLYP) and a G3B3 composite scheme. In the gas phase the calculated energy barriers for N- and/or C-hydroxylation are ca. 100 kJ mol(-1) lower than the barrier for N-chlor...

Uracil, thymine, and 5-fluorouracil (5-FU) have been ferrocenoylated selectively at the N1 position. Deprotonated pyrimidine nucleobases, prepared with sodium hydride (NaH) in N,N-dimethylformamide (DMF), reacted with either ferrocenoyl chloride (FcCOCl) or ferrocenoyl ethyl carbonate (FcCOOCOOEt), in DMF to give a single product. The regioselectiv...

Radical stabilization energies (RSEs) for a wide variety of nitrogen-centered radicals and their protonated counterparts have been calculated at G3(MP2)-RAD and G3B3 level. The calculated RSE values can be rationalized through the combined effects of resonance delocalization of the unpaired spin, electron donation through adjacent alkyl groups or l...

Chlorination of amides is of utmost importance in biochemistry and environmental chemistry. Despite the huge body of data, the mechanism of reaction between amides and hypochlorous acid in aqueous environment remains unclear. In this work, the three different reaction pathways for chlorination of N-methylacetamide by HOCl have been considered: the...

Quantum chemical calculations have been used to model reactions which are important for understanding the chemical fate of paroxetine-derived radicals in the environment. In order to explain the experimental observation that the loss of water occurs along the (photo)degradation pathway, four different mechanisms of radical-induced dehydrations have...

Structural and electronic properties and chemical fate of free radicals generated from hydroxyurea (HU) and its methylated analogues N-methylhydroxyurea (NMHU) and O-methylhydroxyurea (OMHU) are of utmost importance for their biological and pharmacological effects. In this work the cis/trans conformational processes, tautomerizations, and intramole...

Kinetics and mechanisms of the oxidation of methoxyurea and N-methylhydroxyurea were studied in neutral and basic aqueous solutions. The obtained pH dependences of the oxidation rates indicate that for both hydroxyureas the reactive species are the deprotonated ones. The second order rate constants, the activation enthalpies and the activation entr...

Electronic structure methods have been applied to calculate the gas and aqueous phase reaction energies for base-induced rearrangements of N-chloropiperidine, N-chloro-3-(hydroxymethyl)piperidine, and N-chloro-4-(4-fluorophenyl)-3-(hydroxymethyl)piperidine. These derivatives have been selected as representative models for studying the chemical fate...

1,1′-(1-Ferrocenyl-1,3,3-trimethylpropane-1,3-diyl)ferrocene and 1,2-(1-ferrocenyl-1,3,3- trimethylpropane-1,3-diyl)ferrocene are formed as cyclodimeric products during the synthesis of β-ferrocenyl carbinols, in relative ratios which depend on the reaction conditions. Their ratios and stabilities are examined, and calculated at the BP86 level of t...