Manuel Balón

Acid–base and spectral properties of β-carbolines. Part 2. Dehydro and fully aromatic β-carbolines

The absorption and fluorescence spectra of a set of dehydro and fully aromatic β-carboline (9H-pyrido[3,4-b]indole) derivatives have been investigated in aqueous solutions of varying acidity. Within the pH-range, cationic (nitrogen protonation) and neutral species are evidenced from both absorption and fluorescence spectra. Additional zwitterionic species can also be detected from the fluorescence spectra. In highly basic media, outside the pH-range, anionic species (pyrrolic nitrogen deprotonation) are formed. Ground state ionization constants for the different acid–base equilibria involving these species have been determined spectrophotometrically at 25 °C. Lowest excited singlet state pKas have been estimated from the Forster–Weller cycle. The influence of structural variations on the spectra and on the acid–base properties of these compounds is discussed.

The acid-base properties of pyrrole and its benzologs indole and carbazole. A reexamination from the excess acidity method.

Abstract The acid-base equilibria of protonation and deprotonation of pyrrole and its benzologs indole and carbazole have been reexamined using the Excess Acidity Method (E.A.M.).

Dynamic Study of Excited State Hydrogen‐bonded Complexes of Harmane in Cyclohexane–Toluene Mixtures¶

Abstract Photoinduced proton transfer reactions of harmane or 1-methyl-9H-pyrido[3,4-b]indole (HN) in the presence of the proton donor hexafluoroisopropanol (HFIP) in cyclohexane–toluene mixtures (CY–TL; 10% vol/vol of TL) have been studied. Three excited state species have been identified: a 1:2 hydrogen-bonded proton transfer complex (PTC), between the pyridinic nitrogen of the substrate and the proton donor, a hydrogen-bonded cationlike exciplex (CL*) with a stoichiometry of at least 1:3 and a zwitterionic exciplex (Z*). Time-resolved fluorescence measurements evidence that upon excitation of ground state PTC, an excited state equilibrium is established between PTC* and the cationlike exciplex, CL*, λem ≈ 390 nm. This excited state reaction is assisted by another proton donor molecule. Further reaction of CL* with an additional HFIP molecule produces the zwitterionic species, Z*, λem ≈ 500 nm. From the analysis of the multiexponential decays, measured at different emission wavelengths and as a function of HFIP concentration, the mechanism of these excited state reactions has been established. Thus, three rate constants and three reciprocal lifetimes have been determined. The simultaneous study of 1,9-dimethyl-9H-pyrido[3,4-b]indole (MHN) under the same experimental conditions has helped to understand the excited state kinetics of these processes.

The pyrrole ring as hydrogen-bonding π-donor base: an experimental and theoretical study of the interactions of N-methylpyrrole with alcohols

Abstract The interactions of N -methylpyrrole, MPY, with hexafluoroisopropanol, HFIP, trifluoroethanol, TFE, 2-chloroethanol, CLE, and 1-butanol, BU, have been studied by FTIR measurements and ab initio calculations. The experiments, carried out on the OH stretching band of the alcohols, proved the formation of 1:1 stoichiometric hydrogen-bonded complexes in which the OH group acts as H-donor and the aromatic ring as acceptor. DFT calculations with the B3LYP functional and the 6-31++ G** basis sets found minima, for all the complexes, with T-shape geometries, where the OH group of the alcohol points to the C-3 in the aromatic ring of MPY. The experimental association constants and the shifts of the OH bands showed a decrease as the H-donor ability of the alcohol diminishes. These parameters are in qualitative agreement with the stabilization energies and frequency-shifts theoretically calculated. Measurements carried out in different solvents showed that the solvent polarity affects the association constant values, but the shifts of the associated bands keep unchanged.

A fluorescence study of the molecular interactions of harmane with the nucleobases, their nucleosides and mononucleotides.

Fluorescence binding studies of harmane to the elemental components of the nucleic acids were undertaken to investigate the origin of the interaction between the drug and DNA. Most of the tested substrates have been found to induce hypochromism in the absorption spectrum of harmane and to quench its fluorescence. The quenching process induced by the nucleobases and their nucleosides is mainly due to the formation of ground state 1:1 complexes. However, in the case of the mononucleotides a dynamic quenching component is also observed. This quenching component is likely due to the excited state interaction of harmane with the phosphate group of the nucleotides. UV-vis spectral changes and quenching measurements have been used to quantify the ground state association constants of the complexes and the quenching rate constants.

Hydrogen-Bonding Interactions between Harmane and Pyridine in the Ground and Lowest Excited Singlet States

Abstract— A spectroscopic (UV‐visible, Fourier transform IR, steady‐state and time‐resolved fluorescence) study of hydrogen‐bonding interactions between harmane (1‐meth‐yl‐9H‐pyrido/3,4‐b/indole) and pyridine in the ground and lowest excited singlet state is reported. In low polar and weakly or nonhydrogen‐bonding solvents, such as cy‐clohexane, chloroform, carbon tetrachloride, toluene and benzene, the analysis of the spectroscopic data indicates that harmane and pyridine form 1:1 stoichiometric hydrogen‐bonded complexes in both the ground and singlet excited states. The formation constants of the complexes are greater in the excited than in the ground state. Hydrogen‐bonding interaction in the excited state is essential for the quenching of the fluorescence of harmane by pyridine. The stabilities of the hydrogen‐bonded complexes between harmane and pyridine diminish as the polarity and hydrogen‐bonding ability of the solvent increase.

Molecular associations of flavins with betacarbolines and related indoles

The interactions of a set of structurally selected betacarbolines (BC), (9H-pyrido[3,4-b]indoles) and indoles (IND) with two representative flavins (FN): riboflavin (RFN) and flavin mononucleotide (FMN) have been investigated by absorption and fluorescence spectroscopies. Spectral results provided evidence on the formation of 1:1 non-fluorescent molecular complexes, whose stability constants and other related thermodynamic parameters have been estimated from Stern-Volmer quenching analysis. The FMN complexes are somewhat more stable than the RFN complexes. The stabilities of the IND and BC complexes for a given FN follow approximately the order IND approximately tetrahydro BC < dehydro BC < fully aromatic BC. Protonation of the pyridinic nitrogen atom of BCs has a destabilizing effect, which is more pronounced for fully aromatic than for tetrahydro derivatives. The influence of structural factors on the stability of the complexes has been discussed and, aided by theoretical AM1 calculations, a qualitative model for the structure (stacking) and binding forces (cooperative localized charge transfer and dispersion forces) of the complexes has been proposed.

AM1 study of a β-carboline set: structural properties and potential reactivity

A set of β-carbolines derived from norharman and its corresponding dehydro and tetrahydro derivatives has been studied by means of the semiempirical AM1 method. Geometrical parameters, protonation affinities and static reactivity indices have been examined. Structural properties and protonation sites are well described by calculations. Orientation of electrophilic attack on different centres is only partially predicted by the frontier indices. The role of the protonated molecules as reactive species is also discussed.

Hydrogen-bonding and Proton Transfer Interactions between Harmane and Trifluoroethanol in the Ground and Excited Singlet States

A study of the hydrogen‐bonding and proton transfer reactions of the ground and excited states of harmane (1‐methyl‐9H‐pyrido/3,4‐b/indole) and its N9‐methyl derivative with 2,2,2‐trifluoroethanol in cyclohexane is reported. Spectral measurements (UV–visible, Fourier trans‐form IR, steady‐state and time‐resolved fluorescence) show the formation of fluorescent ground‐state hydrogen‐bonded complexes. The results have been interpreted assuming a tautomeric equilibrium between a 1:1 hydrogen‐bonded complex and its 1:2 proton transfer tautomer (hydrogen‐bonding ion pair). Upon excitation to its singlet excited state, the proton transfer tautomer of harmane reacts with an additional 2,2,2‐trifluoroethanol molecule to give a zwitterionic exciplex, which fluoresces at longer wavelength.

Guest–host interactions between tetrahydrobetacarboline and β-cyclodextrin

The interactions between 1,2,3,4-tetrahydro-9H-pyrido[3,4-b]indole or tetrahydrobetacarboline, THBC, and cycloheptaamilose or β-cyclodextrin, β-CD, have been investigated using UV absorption, steady state and time resolved fluorescence measurements. The addition of β-cyclodextrin has very little effect on the absorption spectra of neutral and cationic THBC species. However, it induces a blue shift and pronounced fluorescence enhancements in the emission spectrum of the neutral substrate. Both, steady state and time resolved fluorescence studies show that neutral THBC species form 1:1 inclusion complexes with β-CD. Global analysis of the time resolved data provides evidence on the formation of two different types of 1:1 THBC–β-CD complexes. It is assumed that each one of these complexes corresponds to the two different topologies for the entry of the THBC molecule into the β-CD cavity, i.e. by its benzene or by its piperidinic moiety. Association constants of the complexes and other thermodynamic and photophysical parameters have been estimated from fluorescence measurements.