Fluorescence properties of the anti-tumour alkaloid luotonin A and new synthetic analogues: pH modulation as an approach to their fluorimetric quantitation in biological samples

  • Víctor González-Ruiz, Yamisley González-Cuevas, Sankaralingam Arunachalam, M. Antonia Martín, Ana I. Olives, Pascual Ribelles, M. Teresa Ramos, J. Carlos Menéndez
  • Journal of Luminescence, September 2012, Elsevier
  • DOI: 10.1016/j.jlumin.2012.03.056

What is it about?

Received 26 December 2011 Received in revised form 12 March 2012 Accepted 26 March 2012 Available online 4 April 2012 Keywords: Luotonin A Anti-tumour agents ESPT Steady-state fluorescence UV–Vis-spectrophotometry 1H- and 13C-NMR spectroscopy 1. Introduction Fluorescence techniques have shown a wide range of applica- tion in life sciences including molecular biology and pharmacol- ogy, and also in medical and clinical fields [1–4]. The different fluorescence methodologies display relevant analytical features (selectivity, sensitivity, wide linear response, accuracy and Abbreviations: CE, Capillary electrophoresis; ESPT, Excited state proton transfer reactions; HPLC, High performance liquid chromatography; HTS, High throughput screening; LOD, Limit of detection; LOQ, Limit of quantitation; NMR, Nuclear magnetic resonance; QY, Quantum yield; UV–Vis, Ultraviolet–visible electromag- netic radiation n Corresponding author. Tel.: þ34 91 3941756; fax: þ34 91 3941754. E-mail address: mantonia@farm.ucm.es (M. Antonia Martı ́n). 1 On leave from School of Chemistry, Bharathidasan University, Tiruchirap- palli 620 024, Tamil Nadu, India 0022-2313/$ - see front matter & 2012 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.jlumin.2012.03.056 abstract Luotonin A is an alkaloid structurally related to the natural anti-tumour agent camptothecin. The fluorescence behaviour of luotonin A and a series of six analogues is described in the present work. The influence of solvent polarity and pH on the native fluorescence properties of these alkaloids was studied, finding that in organic solvents or in aqueous solutions (pH 5.5–7.2) the neutral form of the luotonin derivatives emit in the region of 410–450 nm but, in both media, acidification to pH values below 3.0 causes a new emission band to appear at about 500 nm. An ESPT reaction occurs due to the protonation of the basic nitrogen atoms of the pentacyclic ring. Acid-base titrations of luotonin A and its derivatives in aqueous and acetonitrile media were carried out in order to determine their pKna values which were around 2, showing these compounds to be very weak bases. In aqueous media, the absence of an iso-emissive point in the emission spectra suggests the existence of more than two species in the proton transfer equilibria. The basicity of the luotonin A derivatives is increased in organic media, and a good correlation between the pKna values and the chemical structure was found. The protonation of luotonin A was also studied by 1H-NMR and 13C-NMR experiments, which proved the protonation of the nitrogen atoms at the positions 5 and 6 of the pentacyclic ring. The fluorescence quantum yields were determined in ethanol and in aqueous solutions under neutral and acidic conditions. The fluorescence quantum yields were higher in water for the case of the more polar compounds, and the opposite result was obtained for the more hydrophobic ones.

Why is it important?

The remarkable and interesting fluorescence properties of luotonin A prompted the development of its fluorimetric analytical quantitation, obtaining very good analytical features.

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The following have contributed to this page: M. Antonia Martín