José Hidalgo

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.).

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.

Quantum yield and fluorescence lifetime measurements of neutral and cationic species for six β-carboline derivatives

Abstract A study of some emission parameters (quantum yield and fluorescence lifetime) for six alkaloid derivatives of β-carboline is presented. Depending on pH value, various species can exist in solution. In this work we have studied only two of them: cationic and neutral species (see fig. 1). The variation of quantum yield and fluorescence lifetime has been analysed for different substituted β-carboline rings and for some derivatives which do not present the aromatic character on the pyrimidinic nucleus.

An experimental and theoretical study of the acid-base properties of substituted indoles

Abstract Experimental and theoretical studies on the acidity and basicity of a representative set of benzene substituted indoles have been carried out. Aqueous ionization data, obtained spectrophotometrically at 25°C, were comparatively analyzed by the Hammett Acidity function and the Excess Acidity methods. Ionization constants, pKas and solvation m* parameters are reported. Gas-phase ionization enthalpies have been theoretically calculated using the AM1 semiempirical method. Single and double parameter relationships between the theoretical and experimental ionization data and the Hammett substituent constants are observed.

Fluorescence charactersitics of β-carboline alkaloids in highly concentrated hydroxide solutions

Abstract The room temperature electronic absorption and fluorescence spectra of the pharmacologically active β-carboline alkaloids norharman, harmane, harmine, harmaline, reserpine and yohimbine are measured in moderately and highly concentrated hydroxide solutions. The appearance of a new fluorescence emission band in the latter madia for all the compounds under study was ascribed to anions in which the NH group of the indole ring is deprotonated. The differences between the acidities of their excited singlet states and their ground states are estimated by means of the Forster-Weller cycles.

AM1 study of a β-carboline set. Part III: substituent effects

Substituent effects on the protonation and deprotonation processes of the β-carboline ring possessing different degrees of aromaticity have been studied from both an experimental and a theoretical point of view. NO2, Cl, MeO and NH2 groups have been selected. N-7 protonation and N-1 deprotonation enthalpies have been calculated theoretically using the AM1 semiempirical method. Some of the methoxy and nitro derivatives have been synthesized and their acidity constants for the processes mentioned earlier have been determined in aqueous media. From the pK values and the theoretical gas-phase free energy, ΔGgp°, the solvation contribution has been calculated. Substituent effects on the β-carboline system are quite independent of the aromaticity of the ring and the general trends observed in other aromatic systems (such as benzoic acids and phenoxides) for each particular substituent are also found in the β-carboline rings. Some experimental facts on the reactivity of these molecules are discussed in connection with the reactivity indices arising from the wavefunctions.

Acid–base and spectral properties of β-carbolines. Part 1. Tetrahydro-β-carbolines

The absorption and fluorescence spectra of a set of tetrahydro-β-carboline(9H-1,2,3,4-tetrahydropyrido[3,4-b]indole) derivatives in the HI/pH/H– range of –11 to +18 have shown the presence of four different molecular species, namely: dication, cation, neutral and anion. Ionization data for the prototropic equilibria involving these species have been obtained spectrophotometrically at 25 °C and comparatively analysed by the Hammett acidity function and the excess acidity methods. The changes of acidity or basicity experienced by those species upon excitation to their lowest singlet excited states have been estimated from the Forster–Weller cycle. The influence of structural variations on the spectral and acid–base properties of these compounds is discussed.

Dual emission of temperature-induced betacarboline self-associated hydrogen bond aggregates

A systematic study of the influence of the gradual temperature decrease on the UV-vis absorption and fluorescence emission spectra of betacarboline, 9H-pyrido[3,4-b]indole, BC, and other model systems, such as BC plus N(9)-methyl-9H-pyrido[3,4-b]indole, MBC, and BC plus pyridine, PY, has been carried out in 2-methylbutane, 2MB. These studies have allowed the conclusion that the temperature decrease favours the formation of hydrogen-bonded self-associated BC aggregates. The initial red shifts of the absorption and emission bands and the fluorescence quenching have been ascribed to the formation of hydrogen bond BC dimers with a proton transfer structure, PTC. In these adducts, the fluorescence is quenched by an electron-driven proton transfer process. However, because the quenching rate constant decreases upon decreasing the temperature, the emission intensity later increases without modification of the wavelength maxima. At the lowest temperatures, these dimeric PTC complexes further aggregate. We propose that they form ground state cyclic tetrameric adducts in which both nitrogen atoms of each BC unit are hydrogen bonded. The tautomeric forms of these tetrameric complexes, generated by a quadruple proton transfer, emit dual fluorescence, from its locally excited state, LE, and its intramolecular charge transfer state, ICT.