Paulina Pavez

Mechanisms of Degradation of Paraoxon in Different Ionic Liquids

Herein, the reactivity and selectivity of the reaction of O,O-diethyl 4-nitrophenyl phosphate triester (Paraxon, 1) with piperidine in ionic liquids (ILs), three conventional organic solvents (COS), and water is studied by (31)P NMR, UV-vis, and GC/MS. Three phosphorylated products are identified as follows: O,O-diethyl piperidinophosphate diester (2), O,O-diethyl phosphate (3), and O-ethyl 4-nitrophenyl phosphate diester (4). Compound 4 also reacts with piperidine to yield O-ethyl piperidinophosphate monoester (5). The results show that both the rate and products distribution of this reaction depend on peculiar features of ILs as reaction media and the polarity of COS.

Coumarin-based fluorescent probes for dual recognition of copper(II) and iron(III) ions and their application in bio-imaging.

Two new coumarin-based “turn-off” fluorescent probes, (E)-3-((3,4-dihydroxybenzylidene)amino)-7-hydroxy-2H-chromen-2-one (BS1) and (E)-3-((2,4-dihydroxybenzylidene)amino)-7-hydroxy-2H-chromen-2-one (BS2), were synthesized and their detection of copper(II) and iron(III) ions was studied. Results show that both compounds are highly selective for Cu2+ and Fe3+ ions over other metal ions. However, BS2 is detected directly, while detection of BS1 involves a hydrolysis reaction to regenerate 3-amino-7-hydroxycoumarin (3) and 3,4-dihydroxybenzaldehyde, of which 3 is able to react with copper(II) or iron(III) ions. The interaction between the tested compounds and copper or iron ions is associated with a large fluorescence decrease, showing detection limits of ca. 10−5 M. Preliminary studies employing epifluorescence microscopy demonstrate that Cu2+ and Fe3+ ions can be imaged in human neuroblastoma SH-SY5Y cells treated with the tested probes.

Toward a pKa Scale of N-base Amines in Ionic Liquids

An electrochemical technique was used to investigate pKa values of some substituted secondary alicyclic (SA) amines, pyridines (py), anilines (AN), and triethylamine (Et3N) in different ionic liquids. The method involves cyclic voltammetry at a platinized Pt electrode. The experimental data were correlated with pKa values reported previously in aqueous solution, and Hammett parameters were correlated with pKa values in ionic liquids to determine ρ values in these media.

Concerted mechanisms of the reactions of methyl aryl carbonates with substituted phenoxide ions.

The reactions of 4-nitrophenyl, 2,4-dinitrophenyl, and 2,4,6-trinitrophenyl methyl carbonates (NPC, DNPC, and TNPC, respectively) with substituted phenoxide ions are subjected to a kinetic study in water at 25.0 degrees C, ionic strength 0.2 M (KCl). Production of the leaving groups (the nitro derivatives) is followed spectrophotometrically. Under excess of the phenoxide ions pseudo-first-order rate coefficients (k(obsd)) are found throughout. Plots of k(obsd) vs substituted phenoxide concentration at constant pH are linear, with the slope (k(N)) independent of pH. The Brönsted-type plots (log k(N) vs pK(a) of the phenols) are linear with slopes beta = 0.67, 0.48, and 0.52 for the phenolysis of NPC, DNPC, and TNPC, respectively. The magnitudes of these Brönsted slopes are consistent with a concerted mechanism. In the particular case of the phenolysis of NPC the expected hypothetical curvature center of the Brönsted plot for a stepwise mechanism should be pK(a)(0) = 7.1 (the pK(a) of 4-nitrophenol). This curvature does not appear within the pK(a) range of the substituted phenols studied (5.3--10.3), indicating that these reactions are concerted. The phenolysis of DNPC and TNPC should also be concerted in view of the even more unstable tetrahedral intermediates that would be formed if the reactions were stepwise. The reactions of the same substrates with pyridines are stepwise, which means that substitution of a pyridine moiety in a tetrahedral intermediate by a phenoxy group destabilizes the intermediate perhaps to the point of nonexistence. The k(N) values for the title reactions are larger than those for the concerted phenolysis of the corresponding ethyl S-aryl thiolcarbonates. The k(N) values found in the present reactions are subjected to a dual regression analysis as a function of the pK(a), of both the nucleophile and leaving group, the coefficients being beta(N) = 0.5 and beta(lg) = -0.3, respectively. These coefficients are consistent with a concerted mechanism.

Dephosphorylation Reactions of Mono-, Di-, and Triesters of 2,4-Dinitrophenyl Phosphate with Deferoxamine and Benzohydroxamic Acid

This work presents a detailed kinetic and mechanistic study of biologically interesting dephosphorylation reactions involving the exceptionally reactive nucleophilic group, hydroxamate. We compare results for hydroxamate groups anchored on the simple molecular backbone of benzohydroxamate (BHA) and on the more complex structure of the widely used drug, deferoxamine (DFO). BHA shows extraordinary reactivity toward the triester diethyl 2,4-dinitrophenyl phosphate (DEDNPP) and the diester ethyl 2,4-dinitrophenyl phosphate (EDNPP) but reacts very slowly with the monoester 2,4-dinitrophenyl phosphate (DNPP). Nucleophilic attack on phosphorus is confirmed by the detection of the phosphorylated intermediates formed. These undergo Lossen-type rearrangements, resulting in the decomposition of the nucleophile. DFO, which is used therapeutically for the treatment of acute iron intoxication, carries three hydroxamate groups and shows correspondingly high nucleophilic activity toward both triester DEDNPP and diester EDNPP. This result suggests a potential use for DFO in cases of acute poisoning with phosphorus pesticides.

Ionic liquids: anion effect on the reaction of O,O-diethyl O-(2,4-dinitrophenyl) phosphate triester with piperidine

The reactions of O,O-diethyl 2,4-dinitrophenylphosphate triester (1) with piperidine in ionic liquids and four conventional organic solvents (COS) were subjected to kinetic and product studies. Analytical techniques (UV-vis and NMR) identified two pathways: nucleophilic attack at the phosphoryl center and at the C-1 aromatic carbon. The nucleophilic rate constants (kTN) for these parallel reactions were separated into two terms: kPN and kArN for the corresponding electrophilic centers. Both the rate and the selectivities of the reactions are strongly dependent on the nature of the ionic liquid used, and a good correlation with the solvent acceptor capacity to form hydrogen bonds (β) was observed. Remarkably, an exclusive attack at the phosphoryl center was found using [Bmim]DCA, [Bmpyrr]DCA and [Bmpy]DCA as the reaction solvents. In contrast, with [Bmim]PF6 as the reaction solvent, attack at the C-1 aromatic was the main path (94%). These results suggest that ionic liquids can be considered to be designer solvents because by an appropriate choice of the anion it is possible to steer the selectivity of this reaction.

Influence of the ionic liquid on the rate and the mechanism of reaction of p-nitrophenyl acetate with secondary alicyclic amines†

The reaction of p-nitrophenyl acetate (1) with piperidine was studied in nine organic solvents and in nine ionic liquids. The aminolysis of 1 by four different secondary amines was also studied in [Bmim]BF4 and their basicities were determined in this solvent using two different methods. Medium effects were analysed and interpreted by comparing the rate constants of aminolysis for the two sets of solvents.

Photophysics and Photochemical Studies of the Vitamin B6 Group and Related Derivatives

The photophysics and photochemical properties of vitamin B6 constituents and analogs were studied as function of pH and solvent. The pK of the phenolic oxygen and the pyridine ring nitrogen depends on the electron donor‐acceptor ability of the 4‐substituent, and agrees with the calculated proton affinity. For all studied compounds, the fluorescence properties showed that the phenolic oxygen is 8 units more acidic in the lowest singlet excited state than in the ground state. The pyridine N‐atom is slightly more basic in the excited state. At pH of biological significance, pH 6–8, pyridoxamine and 4‐pyridoxic acid are the more efficient chromophores with higher fluorescence yield and longer lifetime. Spectroscopic studies showed that the tautomeric equilibrium depends on the nature of the 4‐substituent. The quenching of the singlet excited state of pyridoxamine and 4‐pyridoxic acid by amino acids, free or in a peptide, and DNA bases at pH 7 was studied by time‐resolved fluorescence techniques. The quenching rate constants are well correlated with the redox properties of the pyridoxinic compound and amino acids, and are related to the free energy change in the electron transfer process. Guanosine and pyrimidine bases also are efficient quenchers, involving an electron transfer reaction.

Substituent effects on reactivity of 3-cinnamoylcoumarins with thiols of biological interest

The Michael addition reactions of the biothiols cysteine, homocysteine, cysteinyl-glycine, γ-glutamyl-cysteine and glutathione with 3-cinnamoylcoumarin derivatives (ChC1–ChC4) in aqueous solution (30 °C, ionic strength 0.2 M KCl) were followed fluorimetrically and evaluated kinetically. The study was completed with a theoretical analysis based on the inverse of the Fukui potential (1/νf (r)), which is proposed for the first time as a local softness descriptor. Thus, considering both experimental results and theoretical analysis, the following conclusions can be drawn: (i) the reactivity of the tested probes towards Michael addition increases in the para-substitution sequence: H < OEt < SMe < Br < NO2, and is not correlated with the σP values of the substituents; (ii) in turn, the descriptor proposed here as local softness (1/νf (r)) appears as a promising reactivity index that is able to explain the higher kN values found for both electron-withdrawing and electron-donating groups; (iii) the nucleophilic reactivity of the biothiols employed increases in the sequence Cys-Gly < Hcy < GSH < Cys < γ-Glu-Cys; and also finally (iv) we have demonstrated that these probes can be used for fluorimetric thiol determination in SH-SY5Y cells.

Kinetic investigation of the phenolysis of phenyl 4-nitrophenyl and phenyl 2,4-dinitrophenyl carbonates

The reactions of phenyl 4-nitrophenyl carbonate (PNPC) and phenyl 2,4-dinitrophenyl carbonate (PDNPC) with a homogeneous series of phenoxide anions are subjected to a kinetic investigation in water at 25.0 °C, ionic strength 0.2 mol dm−3 (KCl). Under phenoxide or total phenol excess over the substrate all these reactions obey pseudo first-order kinetics and are first order in phenoxide. The Bronsted-type plots for the nucleophilic rate constants are linear with slopes 0.61 and 0.49 for the phenolysis of PNPC and PDNPC, respectively. The magnitude of these slopes and the absence of curvature in the Bronsted plot at pKa = 7.1 for the PNPC reactions are consistent with concerted mechanisms (one step) for both reaction series. PDNPC is more reactive than PNPC toward phenoxide nucleophiles; this can be explained by the presence of a second nitro group in PDNPC, which (i) leaves its carbonyl carbon more positively charged than that of PNPC, making the former a better electrophile, and (ii) makes 2,4-dinitrophenoxide a better leaving group than 4-nitrophenoxide. The larger nucleophilic rate coefficients found in this work relative to those obtained in the concerted phenolysis of 4-nitrophenyl and 2,4-dinitrophenyl methyl carbonates is explained by a stronger electron withdrawal from PhO compared to MeO. Comparison of the concerted phenolysis of PNPC with the stepwise reactions of quinuclidines with the same substrate indicates that substitution of a quinuclidino group in a zwitterionic tetrahedral intermediate by a phenoxy group greatly destabilises the intermediate.