Alvaro Cañete

Photoreduction of oxoisoaporphines by amines: laser flash and steady-state photolysis, pulse radiolysis, and TD-DFT studies.

Photoreduction of oxoisoaporphine (OIA) (1-aza-benzo-[de]anthracen-7-one) and its 5-methoxy (5-MeO-OIA) derivative by selected amines (two non-alpha-hydrogen-donating amines (1,4-diaza[2.2.2]-bicyclooctane (DABCO) and 2,2,6,6-tetramethylpiperidine (TMP)) and three alpha-hydrogen-donating amines (triethylamine (TEA), diethylmethylamine (DEMA), and dimethylethylamine (DMEA))) has been studied in deaerated neat acetonitrile solutions using laser flash and steady-state photolysis. The triplet excited states of OIA and 5-MeO-OIA are characterized by intense absorption maxima located at lambda(max) = 450 nm and lifetimes of 34.7 +/- 0.5 and 44.6 +/- 0.4 micros, respectively. In the presence of tertiary amines, both triplets are quenched with a rate constant that varies from the near diffusion limit (>10(9) M(-1) s(-1)) to a rather low value (approximately 10(7) M(-1) s(-1)) and shows the expected dependence on the reduction potential for one-electron-transfer reactions. The transient absorption spectra observed after quenching of the respective triplet states are characterized by distinct absorption maxima located at lambda(max) = 480 and 490 nm (for OIA and 5-MeO-OIA, respectively) and accompanied by broad shoulders in the range of 510-560 nm. They were assigned to either solvent-separated radical ion pairs and/or isolated radical anions. In the presence of alpha-hydrogen-donating amines these species undergo protonation that leads to the formation of neutral hydrogenated radicals A1H(*)/A2H(*) with two possible sites of protonation, N and O atoms. Pulse radiolysis and molecular modeling together with TD-DFT calculations were used to support the conclusions about the origin of transients.

Copper‐Catalyzed Intermolecular Aminooxygenation of Styrenes using N‐Fluorobenzenesulfonimide and Simple Alcohols

The mild and fast copper‐catalyzed radical and regioselective aminoalkoxylation of styrenes by using N‐fluorobenzenesulfonimide and simple alcohols as nitrogen and alkoxy sources, respectively, was investigated. The aminoalkoxylated products obtained could be used in the synthesis of new compounds with possible activity as neurotransmitter receptor ligands.

Efficient Indium-Mediated Dehalogenation of Aromatics in Ionic Liquid Media

An efficient indium-mediated dehalogenation reaction of haloaromatics and haloheteroaromatics in ionic liquids has been studied. This method is simple and effective in the presence of [bmim]Br. Furthermore, this methodology is environmentally friendly compared with conventional ones.

Unexpected Imidazoquinoxalinone Annulation Products in the Photoinitiated Reaction of Substituted‐3‐Methyl‐Quinoxalin‐2‐Ones with N‐Phenylglycine

Photoinduced electron transfer between N‐phenylglycine (NPG) and electronically excited triplets of 7‐substituted‐3‐methyl‐quinoxalin‐2‐ones in acetonitrile generate the respective ion radical pair, where by decarboxylation the phenyl‐amino‐alkyl radical, PhNHCH2•, is generated. This radical reacts with the 3‐methyl‐quinoxalin‐2‐ones ground states, leading to the product 2. Other, unexpected, 7‐substituted‐1,2,3,3a‐tetrahydro‐3a‐methyl‐2‐phenylimidazo[1,5‐a]quinoxalin‐4(5H)‐ones, annulation products, 3a–f, were generated; likely by the addition of two PhNHCH2• radicals, to positions 3 and 4 of the quinoxalin‐2‐ones. The reaction mechanism includes a photoinduced one electron transfer initiation step, propagation steps involving radical intermediates and NPG with radical chain termination steps that lead to the respective products 2a–f and 3a–f and NPG by‐products. The proposed mechanism accounts for the strong dependency found for the initial photoconsumption quantum yields on the electron‐withdrawing power of the substituent. Therefore, photolysis of common reactants widely used such as NPG and substituted quinoxalin‐2‐ones may provide a simple synthetic way to the unusual, unreported tetrahydro‐imidazoquinoxalinones 3a–f.

Spectral and Kinetic Properties of Radicals Derived from Oxidation of Quinoxalin-2-One and Its Methyl Derivative

The kinetics and spectral characteristics of the transients formed in the reactions of •OH and •N3 with quinoxalin-2(1H)-one (Q), its methyl derivative, 3-methylquinoxalin-2(1H)-one (3-MeQ) and pyrazin-2-one (Pyr) were studied by pulse radiolysis in aqueous solutions at pH 7. The transient absorption spectra recorded in the reactions of •OH with Q and 3-MeQ consisted of an absorption band with λmax = 470 nm assigned to the OH-adducts on the benzene ring, and a second band with λmax = 390 nm (for Q) and 370 nm (for 3-MeQ) assigned, inter alia, to the N-centered radicals on a pyrazin-2-one ring. The rate constants of the reactions of •OH with Q and 3-MeQ were found to be in the interval (5.9–9.7) × 109 M–1·s–1 and were assigned to their addition to benzene and pyrazin-2-one rings and H-abstraction from the pyrazin-2-one nitrogen. In turn, the transient absorption spectrum observed in the reaction of •N3 exhibits an absorption band with λmax = 350 nm. This absorption was assigned to the N-centered radical on the Pyr ring formed after deprotonation of the respective radical cation resulting from one-electron oxidation of 3-MeQ. The rate constant of the reaction of •N3 with 3 MeQ was found to be (6.0 ± 0.5) × 109 M–1·s–1. Oxidation of 3-MeQ by •N3 and Pyr by •OH and •N3 confirms earlier spectral assignments. With the rate constant of the •OH radical with Pyr (k = 9.2 ± 0.2) × 109 M–1·s‒1, a primary distribution of the •OH attack was estimated nearly equal between benzene and pyrazin-2-one rings.

Spectral and Kinetic Study of 3-Methylquinoxalin-2-ones Photoreduced by Amino Acids: N-Phenylglycine Radical Chain Reactions and N-Acetyltryptophan Decarboxylation

Transient intermediates were identified in the photoreduction of 3-methylquinoxalin-2-one derivatives by N-phenylglycine, NPG, and N-acetyltryptophan, NAT. For both reductants it can be postulated a sequence of reaction comprising first a photoinduced single electron transfer followed by a proton transfer from the radical cation of the electron donor to the radical anion of the 3-methylquinoxalin-2-one giving rise to the reported products. The effect of the concentrations of NPG and the quinoxalin-2-one on the rate of photoconsumption of this last were quantified, and the lifetimes of the possible intermediates estimated. In the photoreduction by NAT, processes leading to the decarboxylation of NAT and radical adduct product compete with the expected SET from the indoyl N to the excited triplet of quinoxalin-2-ones as revealed by the detection of the deprotonated N-acetyltryptophan radical [NAT-H](•). This radical is formed almost instantly after the laser pulse and has a secondary delayed growth via a delayed proton transfer from the indoyl radical cation NAT(•+) to the quinoxalin-2-one radical anions. The decarboxylation of NAT that mimics C-terminus tryptophan in proteins is biologically relevant because might cause damages at cellular and the whole organism level. As far as we know this is the first report of a radical decarboxylation of N-acetyltryptophan leading to photoproducts.

Inclusion of Ethyl Acetoacetate Bearing 7‐Hydroxycoumarin Dye by β‐Cyclodextrin and its Cooperative Assembly with Mercury(II) Ions: Spectroscopic and Molecular Modeling Studies

The inclusion of the fluorescent organic dye, ethyl 3-(7-hydroxy-2-oxo-2H-chromen-3-yl)-3-oxopropanoate (1) by the host β-cyclodextrin (β-CD), and its response toward mercuric ions (Hg2+ ), was studied by UV/Vis, fluorescence, and 1 H NMR spectroscopic analyses, mass spectrometry and molecular modeling studies. 1 H NMR measurements together with molecular modeling studies for dye 1 demonstrate that it exhibits two tautomeric forms (keto and enol); however, when the dye is included into the β-CD cavity, the enol form predominates. Moreover, by using spectroscopic and spectrometry techniques, a 1:1 stoichiometry was determined for the complexes formed between dye 1 (enol form) and β-CD, with a binding constant (Kb1 =1.8×104  m-1 ) and for the dye 1 (keto form)-Hg2+ (Kb2 =2.3×103  m-1 ). Interestingly, in the presence of 1-β-CD complex and mercuric ions, a ternary supramolecular system (Hg-1-β-CD complex) was established, with a 1:1:1 stoichiometry and a Kb3 value of 4.3×103  m-1 , with the keto form of the dye being the only one present in this assembly. The three-component system provides a starting point for the development of novel and directed supramolecular assemblies.

SCAVENGING ACTIVITY OF DICLOFENAC: INTERACTION WITH ABTS RADICAL CATION AND PEROXYL RADICALS

ABSTRACT The scavenging activity of diclofenac was estimated by its capability to bleach ABTS radical cation, and ORAC (oxygen radical absorbance capacity) methodology. In addition, GC-MS technique was used to establish if the lactamic derivative of diclofenac was formed as final product in the interaction with peroxyl radicals. Diclofenac bleached ABTS radical cation in a concentration-dependent way. In ORAC assays, diclofenac inhibited the consumption of fluorescein and c-phycocyanin mediated by peroxyl radicals. An ORAC-fluorescein, and ORAC-c-phycocyanin value of 0.3, and 0.004 was estimated, respectively. From the downcurvature observed in Stern-Volmer-like plots, we postulated that the low protection of c-phycocyanin is related to secondary damage of c-phycocyanin by the secondary radical of diclofenac. By GC-MS studies only a 2,6-dichloroaniline derivative was detected as product after the reaction with peroxyl radicals. Key Words: Diclofenac, fluorescein, c-phycocyanin, ORAC, scavenging activity.

Controlled keto–enol tautomerism of coumarin containing β-ketodithioester by its encapsulation in cucurbit[7]uril

Conventional spectroscopy techniques (UV-Vis, fluorescence and NMR), mass spectrometry and molecular modeling studies are used to assess the inclusion of cucurbit[7]uril (CB7) with coumarin 7-N,N-diethylamino-2H-chromen-2-one derivatives bearing ethyl acetoacetate (CAM1) and methyl β-ketodithioester (CAM2) moieties. For the first time, it has been demonstrated that the macrocycle CB7 is able to stabilize the keto tautomeric form of both coumarin derivatives. More interestingly, it was also seen that for CAM2, the macrocycle CB7 shifts the keto–enol equilibrium from its enol form to the keto tautomer after its inclusion, establishing important differences with inclusion in β-CD, while for CAM1, the macrocycle CB7 maintains the original keto form.

Photoreduction of Azaoxoisoaporphines by Amines: Laser Flash and Steady-State Photolysis and Pulse Radiolysis Studies†

Photoreduction of 7H‐benzo[e]perimidin‐7‐one (3‐AOIA, A1) and its 2‐methyl derivative (2‐Me‐3‐AOIA, A2) by non‐H‐donating amines (1,4‐diazabicyclo[2.2.2]octane [DABCO]; 2,2,6,6‐tetramethylpiperidine [TMP]), and a hydrogen‐donating amine (triethylamine [TEA]), has been studied in deaerated neat acetonitrile solutions using laser flash photolysis (LFP) and steady‐state photolysis. The triplet excited states of A1 and A2 were characterized by a strong absorption band with λmax = 440 nm and lifetimes of 20 and 27 μs respectively. In the presence of tertiary amines, both triplet excited states were quenched with rate constants close to the diffusional limit (kq ranged between 109 and 1010 M−1 s−1). The transient absorption spectra observed after quenching with DABCO and TMP were characterized by maxima located at 460 nm and broad shoulders in the range of 500–600 nm. These transient species are attributed to solvent‐separated radical ion pairs and/or to isolated radical anions. In the presence of TEA, these transients undergo proton transfer, leading to the neutral hydrogenated radicals, protonated over the N1‐ and O‐atoms. Transient absorption spectra of these transients were characterized by maxima located at 400 and 520 nm and 430 nm respectively. Additional support for these spectral assignments was provided by pulse radiolysis (PR) experiments in acetonitrile and 2‐propanol solutions.