Diprotonation process of meso-tetraphenylporphyrin derivatives designed for photodynamic therapy of cancers: from multivariate curve resolution to predictive QSPR modeling.

Abstract

Tetrapyrrole rings possess four nitrogen atoms, two of which act as Bröndsted bases in acidic media. The two protonation steps occur on a close pH range, particularly in the case of meso-tetraphenylporphyrin (TPP) derivatives. If the cause of this phenomenon is well known--a protonation-induced distortion of the porphyrin ring--data on stepwise protonation constants and on electronic absorption spectra of monoprotonated TPPs are sparse. A multivariate approach has been systematically applied to a series of glycoconjugated and hydroxylated TPPs, potential anticancer drugs usable in Photodynamic Therapy. The dual purpose was determination of protonation constants and linking substitution with basicity. Hard-modeling version of MCR-ALS (Multivariate Curve Resolution Alternating Least Squares) has given access to spectra and distribution profile of pure components. Spectra of monoprotonated species (H(3)TPP(+)) in solution resemble those of diprotonated species (H(4)TPP(2+)), mainly differing by a slight blue-shift of bands. Overlap of H(3)TPP(+) and H(4)TPP(2+) spectra reinforces the difficulty to evidence an intermediate form only present in low relative abundance. Depending on macrocycle substitution, pK values ranged from 3.5±0.1 to 5.1±0.1 for the first protonation and from 3.2±0.2 to 4.9±0.1 for the second one. Inner nitrogens' basicity is affected by position, number and nature of peripheral substituents depending on their electrodonating character. pK values have been used to establish a predictive Multiple Linear Regression (MLR) model, relying on atom-type electrotopological indices. This model accurately describes our results and should be applied to new TPP derivatives in a drug-design perspective.

• Authors: Benoît Chauvin, Athena Kasselouri, Pierre Chaminade, Rita Quiameso, Ioannis Nicolis, Philippe Maillard, Patrice Prognon
• Journal: Analytica chimica acta (Anal Chim Acta) Vol. 705 Issue 1-2 Pg. 306-14 (Oct 31 2011) ISSN: 1873-4324 [Electronic] Netherlands
• PMID: 21962373 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier B.V. All rights reserved.

Chemical References

• Antineoplastic Agents
• Porphyrins
• Protons
• tetraphenylporphyrin

Topics

• Antineoplastic Agents (chemistry)
• Humans
• Multivariate Analysis
• Neoplasms (drug therapy)
• Photochemotherapy
• Photoelectron Spectroscopy (methods)
• Porphyrins (chemistry)
• Protons
• Quantitative Structure-Activity Relationship