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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 method requires only two fluorescence measurements at different known vertical axis positions (z- positions) of the optical element for the same sample. Samples of quinine sulfate, both pure and in mixtures with potassium dichromate, showed a linear dependence of corrected fluorescence on fluorophore concentration (R2 > 0.999), up to Aex ≈ 2 and Aem ≈ 0.5. The correction extended linear fluorescence response over ≈98% of the concentration range with ≈1% deviation of the calibration slope, effectively eliminating the need for sample dilution or separate absorbance measurements to account for IFE. The companion numerical IFE correction method further eliminates the need for any geometric parameters with similar results. Both methods are available online at https://ninfe.science.

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 postoji velik broj primjera koji svjedoče o važnosti stereokemije, u ovome radu dan je pregled nekoliko najznačajnijih i najreprezentativnijih slučajeva u farmaciji., Investigation of the stereoisomerisation process is of the utmost importance in pharmaceutical chemistry and biomedicine. Different isomers can exhibit significant differences when interacting with biological macromolecules, which may result in their modified pharmacokinetic and pharmacodynamic properties, thereby showing different therapeutic and undesirable effects. Although there are numerous examples illustrating the importance of stereochemistry, this article presents an overview of the most significant and representative cases in pharmacy.

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 quantification of substituent effects in the HAT step of the reaction on both nitrogen and carbon atoms, optimized synthetic strategies are outlined for the racemic as well as the stereoselective synthesis of nicotine. This latter process can be achieved using common nitrogen protecting groups, such as Ac, TFAc, and Boc. The said protecting groups show superior nitrogen radical activation as compared to the commonly used Tosyl group. Computational results indicate that the 1, 5-HAT step is in this case likely to work even for the reaction with primary unactivated carbon centers.

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 a more polar solvent, for example, in dimethylsulfoxide (DMSO), the two isomers interconvert to each other. The N7/N9 isomerization was followed by 1H NMR spectroscopy, until dynamic equilibrium was reached. Both kinetics and thermodynamics of the transacylation process are governed by a C6-substituent on the purine ring (R = NH2, Me, NHBz, OBz). The observed rate constant for the N7/N9-isomerization in the adenine system (R = NH2) is kobs = 0.3668 h-1, whereas the corresponding process in the C6-benzyloxypurine is 56 times slower. By use of density functional theory calculations and molecular dynamics simulations, several reaction pathways were considered and explored. Only the reaction mechanism involving DMSO as a nucleophilic reactant is in harmony with the experimental kinetic data. The calculated barrier (ΔG⧧ = 107.9 kJ/mol; at the M06L/6-311+G(d,p)/SDD level of theory) for this SN2-like reaction in the adenine system agrees well with the experimental value of 102.7 kJ/mol. No isomerization was detected in other organic solvents, for example, acetonitrile, N,N-dimethylformamide, or acetone, which indicated the exceptional nucleophilicity of DMSO. Our results raise a warning when treating or dissolving acylated purines in DMSO as they are prone to isomerization. We observed that the N7/N9-group transfer was specific not only for the organometallic moiety only, but for other acyl groups in purines as well. The relevance of this isomerization may be expected for a series of nucleobases and heterocyclic systems in general.

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-ferrocenyl)decane dithiol, surface immobilization on gold failed. Instead, in the presence of gold, molecular decomposition took place, resulting in sulfur-based adlayers and well-defined molecular elimination products, for which we provide spectroscopic evidence. Careful control experiments and comparison with related ferrocene compounds provide insight into the mechanism of the observed elimination reactions, as a combined effect of the molecular structure and the nature of the gold/sulfur bond. These findings, thus, have a broader impact on the design of molecular adlayers, for example, in the context of surface functionalization in sensing or the synthesis of gold nanoparticles.

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, Reichardt, McRae and Suppan solvatochromic methods. The dipole moment of Zaleplon ground state in the gas phase has been calculated as μg = 10.95 D (TD-DFT) with B3LYP/cc-pVTZ functional. There is a good agreement of theoretical data with Reichardt, McRae, and Suppan correlations, while some dissidence with Lippert–Mataga and Bakhshiev equations is suggesting the occurrence of specific solute–solvent interactions. Additionally, multiple linear regression analysis with Kamlet–Taft and Catalan solvatochromic models was applied to solute–solvent interactions. Dominant property of the solvent that affects the absorption band and Stokes shifts of Zaleplon is polarity of the solvent while the emission band is influenced mainly by solvent basicity.

Modern synthetic approaches try to incorporate already known chemical entities and then modify them using late-stage functionalization (LSF) procedures. Hofmann–Löffler–Freytag (HLF) reaction was originally discovered by Hofmann [1–3] in synthetic studies of unconventional N- halo amines. This reaction has the ability to functionalize inactivated C-H bonds and thus belongs in the LSF toolbox. Recently, Del Castillo and Muñiz [4] have modified the HLF reaction for stereoselective nicotine synthesis. Their modification implies an experimental trial and error approach. On the other hand, the quantum chemical approach provides the means for the theoretical determination of parameters that guide the intramolecular HAT step which constitutes the essence of the HLF reaction as well as evaluating the role of the substituents. Therefore, emphasis is set on these parameters, which include the stability of N- and C-centered radicals and the activation barrier. In pursuit after them, N-H bond dissociation energies and related stability values of N-centered radicals, as well as stability values of C-centred radical and corresponding C-H bond dissociation energies are calculated, and with the implementation of the Bell-Evans- Pollany principle, the corresponding activation barriers for the crucial HAT step is obtained. Finally, particular attention is given to prevalent organic solvents that may have an effect on the stability of radicals besides themselves participating in rearrangement steps. Establishing a clear picture of the underlying parameters and the role that substituents have on the crucial step may streamline HLF reaction in accordance with green chemistry principles.

5-Fluorouracil (5-FU) is a pyrimidine antimetabolite introduced in the clinic as an anticancer drug. The reaction between 5-FU and hypochlorous acid (HOCl) is the fundamental process which can occur in activated neutrophils in cancer patients [1] or during chemical treatment of wastewaters [2]. This study combines synthesis, NMR and MS spectroscopy, quantum chemical calculations, and toxicity experiments on Daphnia magna to investigate chemical fate of 5-FU in chlorinated environment. All structures were fully optimized with the B3LYP functional. The standard 6-31+G(d) basis set was used for geometry optimizations and frequency calculations. Improved energetics have been calculated using B2K-PLYP functional and 6- 311+G(3df, 2p) basis set. Gibbs energies of solvation were determined using the SMD continuum solvation model at the B3LYP/6- 31+G(d) level (ε = 78.4). Two explicit water molecules were found as „the ideal number of solvent molecules” for a reliable description of the corresponding potential energy surfaces. The first chlorinated product chlorohydrin 3a was less toxic than the parent 5-FU, suggesting the beneficial effect of chlorination (Figure 1). Further chlorination leads to N1- chlorinated intermediate 6, that undergoes pyrimidine ring opening reaction. The final product 11 was obtained after the loss of the chlorinated urea fragment. This is the most potent compound in the reaction sequence, with toxicity parameter EC50 more than twice lower compared to the parent 5-FU. Interplay between experimental and theoretical procedures, to properly describe reaction pathways and provide more information on toxicity profiles, is a way forward in environmental science research. [1] C. C. Winterbourn, A. J. Kettle and M. B. Hampton, Ann. Rev. Biochem. 85 (2016) 765- 792. [2] J. L. Acero, F. J. Benitez, F. J. Real and G. Roldan, Water Res. 44 (2010) 4158-4170.

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−1) was determined earlier, but the exact mechanism of enantiomerization is not known. Four different mechanisms have been proposed in the literature: C3–H/H exchange reaction, keto–enol tautomerization, solvolytic identity reaction, and ring-chain tautomerization. However, none of the reported reactions has been confirmed as the main pathway for racemization. In this work, all these mechanisms were subjected to comprehensive analysis performed by high-level quantum-chemical models. Two density functionals (B3LYP and M062X) were employed for geometry optimization of all stationary points at the corresponding potential surfaces, and the double-hybrid model (B2PLYP) was used for improved energy calculations. Out of all the tested mechanisms, only the ring-chain tautomerism fits the two experimental targets: the measured energy barrier and the pH-rate profile of racemization. The latter reveals that no acid/base catalysis is required for racemization to occur. The ring-chain tautomerism is initiated by intramolecular proton transfer from the C3-hydroxyl group to the imine nitrogen, which triggers the benzodiazepine ring opening and the formation of the achiral aldehyde intermediate. The latter undergoes ring closure which results in the inverted configuration at the C3-chiral atom of oxazepam. Our computational results suggest that the same mechanism is operative in the fast racemization of different 1,4-benzodiazepines, which posses the hydroxyl group at the stereogenic C3-centre (e.g. lorazepam or temazepam). In other benzodiazepine members (e.g. cinazepam or camazepam) the keto–enol tautomerization and/or the C3–H/H exchange mechanism may become relevant for their much slower racemization. This computational study is not only revealing in terms of mechanistic details, but also has predictive power for optical stability estimates in the family of benzodiazepines and similar heterocycles.

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 concentration in the blood. To determine the most prominent features responsible for binding of 20 different flavonoid aglycones to the IIA region of HSA, in vitro fluorescence measurements and density functional theory (DFT) calculations were conducted. These results were then integrated to elucidate structure–affinity relationships. The presented results reveal that flavones and flavonoles bind most strongly to the IIA region of HSA. There are several electronic and structural determinants associated with flavonoid binding to this HSA region: high C3 nucleophilicity and partial charge of O4, high HOMO and LUMO energies, and coplanarity of AC and B rings. Both steric and electronic characteristics of flavonoids have a great impact on their binding to HSA, with hydrogen donor and acceptor properties and coplanarity being the most prominent.

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 regioselectivity of these reactions were analyzed in detail by using NMR spectroscopy and quantum chemical calculations. The 1H and 19F NMR spectra of reaction mixtures, and 13C NMR and 2D NOESY spectra of products, confirmed the formation of the N1-isomer only. The calculated energy barrier for acetylation at the N3-position is significantly higher (> 40 kJ/mol), which suggests that the analogous reaction at the N1-position is kinetically controlled. The nucleophilic addition of pyrimidine bases to the carbonyl group of FcCOCl proceeds through a concerted SN2-like mechanism with the absence of the generally assumed tetrahedral intermediate.

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 lone pairs, and through inductive electron donation/electron withdrawal. The influence of ring strain effects as well as the synergistic combination of individual substituent effects (captodatively stabilized N-radicals) have also been explored. In symmetric N-radicals the substituents may also affect the relative ordering of electronic states. In most cases the p-type radical (unpaired spin distribution perpendicular to the plane of the N-radical) is found to be most stable. Closed shell precursors of biological and pharmaceutical relevance, for which neither experimental nor theoretical results on radical stabilities exist, have been included.

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-chlorination of amines. In the model solvent, however, the latter process becomes kinetically more favored. The explicit solvent effects are crucial for determination of the reaction mechanism. The N-chlorination is extremely susceptible to the presence of explicit water molecules, while no beneficial solvation effect has been found for the N- or C-hydroxylation of amines. The origin of the observed solvent effects arises from differential solvation of the respective transition states for chlorine- and oxygen-transfers, respectively. The nature of solvation of the transition state structures has been explored in more detail by classical molecular dynamics (MD) simulation. In agreement with the quantum mechanical approach, the most stable structural motif, which includes the amine, HOCl, and two reactive waters, has been identified during the MD simulation. The inclusion of 5 or 6 explicit water molecules is required to reproduce the experimental barriers for HOCl-induced formation of N-chloramines in an aqueous environment.

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) and calculated (271–293 mV) values for reduction potential E°’ show that these conjugates are much better oxidants than the parent ferrocene system. In search for the computational model, which can successfully reproduce experimental results, the M06-2X functional appeared as the optimal method in terms of efficiency and accuracy. This work is licensed under a Creative Commons Attribution 4.0 International License.

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 solution volume, cost-effective electrode replacement and automated measurement. This method can easily be applied to the study of similar systems in aqueous media and might be of particular importance in the momentous field of glycomics, where large numbers of protein isoforms need to be characterized. Keywords: Transferrin, Reduction potential, Spectroelectrochemistry, Indium‑tin oxide, Methyl viologen

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 adduct were reduced to hydroxyl groups with sodium borohydride. This apparently straightforward reaction proceeds in a highly stereoselective fashion to yield the title ferrocenyl nucleoside as a racemic mixture that consists of the R,R and the S,S isomers. The absolute configuration of the chiral carbon atoms in the nucleoside was assigned on the basis of single-crystal X-ray diffraction analysis of the methyl derivative. Furthermore, the mechanism of reduction of the bis(thymine) adduct was investigated by using DFT calculations. The two critical minima, pre-reactive complex, and semi-reduced intermediate, as well as two corresponding transition states were located to support the observed stereoselectivity. The redox properties of 1,1'-bis(thymine)ferrocene nucleoside, its precursor, and congeners were investigated using cyclic voltammetry. For the title compound a reversible redox process was found at a low potential of -30 mV versus FcH/FcH

In order to perform a complete search for prereactive complexes between arenes (benzene and triazine) and chlorine, stochastic search method was employed. All stationary points were optimized at B3LYP, M05-2X, and MP2 levels, while improved energetics have been calculated using B2PLYP-D method which includes van der Waals corrections important for accurate description of dispersion forces. Several new intermediates, not reported earlier, have been located and their mechanistic relevance has been discussed. It is suggested that in the case of chlorination of benzene the T-shaped complex precedes the formation of classical pi-complex. No Wheland sigma-complex has been found on the corresponding energy surface, unless explicit counterions (BF4- or AlCl4-) are included in calculations. Neither pi- nor sigma-complexes were located on the reactant side of chlorination of triazine, but only linear and T-shaped complexes are identified as stable minima. These structures are proposed as important prereactive complexes on the reaction coordinate for chlorination of triazine.

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 intramolecular hydrogen and methyl migrations in hydroxyurea-derived radicals have been considered. Potential energy profiles for these reactions have been calculated using two DFT functionals (BP86 and B3LYP) and two composite models (G3(MP2)RAD and G3B3). Solvation effects have been included both implicitly (CPCM) and explicitly. It has been shown that calculated energy barriers for free radical rearrangements are significantly reduced when a single water molecule is included in calculations. In the case of HU-derived open-shell species, a number of oxygen-, nitrogen-, and carbon-centered radicals have been located, but only the O-centered radicals (e1 and z1) fit to experimental isomeric hyperfine coupling constants (hfccs) from EPR spectra. The reduction of NMHU and OMHU produces O-centered and N-centered radicals, respectively, with the former being more stable by ca. 60 kJ mol−1. The NMHU-derived radical e4 undergoes rearrangements, which can result in formation of several conceivable products. The calculated hfccs have been successfully used to interpret the experimental EPR spectra of the most probable rearranged product 10. Reduction potentials of hydroxyureas, radical stabilization energy (RSE) and bond disocciation energy (BDE) values have been calculated to compare stabilities and reactivities of different subclasses of free radicals. It has been concluded, in agreement with experiment, that reductions of biologically relevant tyrosyl radicals by HU and NMHU are thermochemically favorable processes, and that the order of reactivity of hydroxyureas follows the experimentally observed trend NMHU > HU > OMHU.

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 water. In the search for the most feasible pathways of HOCl-induced transformations of CBZ, a quantum chemical approach was employed. Chlorination and epoxidation of CBZ are two initial, competitive processes that result in two key intermediates: N-chloramide and 10,11-epoxide. The calculated free energy barriers (ΔG‡293) for these reactions are 105.7 and 95.7 kJ mol−1 resp., which is in agreement with the experimental energy barrier of 98.2 kJ mol−1. All transformation products detected in chlorination experiments were located by computational models, and the reaction mechanism underlying their formation was described in detail. Different computational methods (density functional and ab initio theory) were applied, and the double hybrid B2-PLYPD functional was found to be superior in terms of efficiency and accuracy. Of special interest are oxoiminostilbene and formylacridine, which are the final products in the degradation cascade. Their exceptional thermodynamic stability, as predicted by quantum chemical methods, suggests that these structures should be considered as recalcitrants in chlorinated waters. Fruitful interplay between computational models and experimental data proves that the quantum chemical approach can be used as a predictive tool in environmental degradation studies.

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 one-step N-chlorination of the amide, the chlorination via O-chlorinated intermediate, and the N-chlorination of the iminol intermediate. The high-level quantum chemical G3B3 composite procedure, double-hybrid B2-PLYPD, B2K-PLYP methods, and global hybrid M06-2X and BMK methods have been employed. The calculated energy barriers have been compared to the experimental value of ΔG(#)298 ≈ 87 kJ/mol, which corresponds to reaction rate constant k(r) ≈ 0.0036 M(-1) s(-1). Only the mechanism in which the iminol form of N-methylacetamide reacts with HOCl is consistent (ΔG(#)298 = 87.3 kJ/mol at G3B3 level) with experimental results. The analogous reaction mechanism has been calculated as the most favorable pathway in the chlorination of small-sized amides and amide-containing pharmaceuticals: carbamazepine, acetaminophen, and phenytoin. We conclude that the formation of the iminol intermediate followed by its reaction with HOCl is the general mechanism of N-chlorination for a vast array of amides.

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 been considered. The elimination of water from the N-centered radical cation, which results in the formation of an imine intermediate, has been calculated as the most feasible process. The predicted energy barrier (ΔG#298 = 98.5 kJ mol−1) is within the barrier limits set by experimental measurements. All reaction intermediates and transition state structures have been calculated using the G3(MP2)-RAD composite procedure, and solvent effects have been determined using a mixed (cluster/continuum) solvation model. Several new products, which comply with the available experimental data, have been proposed. These structures could be relevant for the chemical fate of antidepressant paroxetine, but also for biologically and environmentally related substrates.

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 of environmentally relevant chloramines. The performance of different computational methods (MP2, MP4, QCISD, B3LYP and B2PLYP) for calculating the thermochemistry of rearrangement reactions was assessed. The latter method produces energies similar to those obtained at G3B3(+) level, which themselves have been tested against experimental results. Experimental energy barriers and enthalpies for ring inversion, nitrogen inversion and dehydrochlorination reactions in N-chloropiperidine have been accurately reproduced when solvent effects have been included. It was also found that the combined use of continuum solvation models (e.g. CPCM) and explicit consideration of a single water molecule is sufficient to properly describe the water-assisted rearrangement of N-chlorinated compounds in basic media. In the case of N-chloro-4-(4-fluorophenyl)-3-(hydroxymethyl)piperidine, which represents the chlorinated metabolite of the antidepressant paroxetine, several different reactions (intramolecular addition, substitution, and elimination reactions) have been investigated. Transition state structures for these processes have been located together with minimum energy structures of conceivable products. Imine 4A is predicted to be the most stable reaction product, closely followed by imine 4B and oxazinane 8, while formation of isoxazolidine 7 is much less favourable. Calculated reaction barriers in aqueous solution are quite similar for all four processes, the lowest barrier being predicted for the formation of imine 4A.

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 entropies for the reactions of methoxyurea (O-methylhydroxyurea) and N-methylhydroxyurea anions with Fe(CN)6 3− at 25 oC, I = 2 mol dm−3 (NaClO4) were determined as (5.06 ± 0.01) x 102 mol−1 dm3 s−1, (1.92 ± 0.02) x 104 mol−1 dm3 s−1, 27 ± 1 kJ mol−1, 16 ± 1 kJ mol−1, −101 ± 2 J mol−1 K−1, and −107 ± 4 J mol−1 K−1, respectively. The pKa value of methoxyurea at 25 oC and 2 mol dm−3 ionic strength was determined kinetically as 12.7 ± 0.1 and the thermodynamic parameters for the deprotonation reaction were determined as ΔaH = 43 ± 1 kJ mol−1, and ΔaS = −96 ± 4 J mol−1 K−1. When the kinetic results are compared with the data reported for hydroxyurea, an inverse dependence of the rate constants on the pKa of the hydroxyurea derivatives at 25 oC is observed. Such unexpected behaviour has been explained by the ab initio calculations and NBO analysis of HOMOs for all three hydroxyureates. (doi: 10.5562/cca1799)

Herbicides are chemical molecules used for destruction of weeds. Massive usage of herbicides has resulted in two global problems: increase in weed resistance and harmful impact of human health [1, 2]. In order to facilitate development of novel, more specific herbicides and of strategies for impeding the weed resistance, we have carried out extensive in silico analysis of the set of herbicides. Herein, we present results revealing links between structural, physicochemical, ADME (Absorption, Distribution, Metabolism, Excretion) and toxic features for herbicides (Figure 1). The analysis has been done by using proper machine learning approaches. References: [1] A. Forouzesh, E. Zand, S. Soufizadeh, S. S. Foroushani, Weed Res. 55 (2015) 334-358. [2] V. I. Lushchak, T. M. Matviishyn, V. V. Husak, J. M. Storey, K. B. Storey, EXCLI J. 17 (2018) 1101-1136.