Characterization of isomeric cationic porphyrins with β-pyrrolic substituents by electrospray mass spectrometry: The singular behavior of a potential virus photoinactivator

Abstract

Electrospray ionization mass spectrometry (ESI-MS) and tandem mass spectrometry (ESI-MS/ MS) have been used to differentiate the 2-and 4-methylpyridyl isomers of free-base and metallated cationic ␤-vinylpyridylporphyrins. The analysis by ESI-MS/MS of the deuterated analogs and semiempirical calculations of structural and electronic parameters were also undertaken. The two free-base isomers are easily differentiated by ESI-MS/MS but the presence of a metallic center renders differentiation of the metallated isomers less effective. The data acquired show that of all the studied compounds, the free-base 2-methylpyridyl isomer, which was operative in the in vitro photoinactivation of Herpes simples virus, has a different gas-phase behavior. Local distortion of the macrocycle due to the presence of the ␤-vinylpyridyl substituent occurs for all the compounds, but a different electron density distribution can account for the observed gas-phase behavior of this potential virus photoinactivator. (J Am Soc Mass Spectrom 2007, 18, 218 -225 Viruses are responsible for a large number of infectious diseases. In particular, the Herpes simplex virus is one of the most common agents responsible for viral infections in man [5]. From preliminary virus inactivation studies carried out with Herpes simplex virus type 1 (HSV-1) using the cationic porphyrins 1 and 2 (Scheme 1), we have observed that despite their structural resemblance and their similar photocytotoxicity profiles, Compound 1 was very effective in the photoinactivation of the virus, whereas Compound 2 displayed no virucidal effect in the same conditions [6].Electrospray ionization mass spectrometry (ESI-MS) was successfully applied to characterize porphyrins as early as 1991 [7] and both ESI-MS [8 -11] and tandem mass spectrometry (ESI-MS/MS) [12,13] have been used to study neutral and cationic porphyrins since then. We wanted to know if the two porphyrin isomers, 1 and 2, could be differentiated by ESI-MS/MS and if the informa-

Structural Effects of the β-Vinyl Linker in Pyridinium Porphyrins: Spectroscopic Studies in Organic Solvents and AOT Reverse Micelles

“…Previous semiempirical calculations on the electronic charge distribution on carbon atoms of compound 1 account for a negative charge density on carbon C-1″ (Figure 8) adjacent to the vinylic double bond and to the positive pyridinium nitrogen. 18 In order to search for possible alterations in the ground state that could explain the puzzling spectral changes induced in alcoholic solvents, we acquired the 1 H NMR spectra of compounds 1 and 2 in deuterated chloroform and deuterated chloroform/methanol mixtures (Figures S6 and S7, Supporting Information), before and after irradiation. From those experiments, the high stability of the trans configuration for both isomers is clear.…”

β-Formyl- and β-Vinylporphyrins: Magic Building Blocks for Novel Porphyrin Derivatives

“…Interestingly, the two free-base isomers 16a and 16b were easily differentiated by ESI-MS and ESI-MS/MS studies [ 101 ]. Semi-empirical calculations allowed to conclude that the different electron density distribution was the responsible for the different gas phase behaviour of the two isomers and not the local distortion due to the presence of the β-vinylpyridyl substituents.…”

Electrospray Tandem Mass Spectrometry of β-Nitroalkenyl Meso-Tetraphenylporphyrins

“…In particular, tandem mass spectrometry (MS/MS) has been used for the structural characterisation of porphyrin derivatives. [18][19][20][21][22][23][24][25][26] An MS/MS analysis has the advantage of allowing a rapid and efficient identification of porphyrins in mixtures from synthetic procedures, even paramagnetic ones [not possible by nuclear magnetic resonance (NMr), unless specific NMr techniques are used], without rigorous clean-up. 18 these advantages are even more significant when the assessment of structural modifications occurring in in vivo cellular metabolism is required.…”