Synthesis, characterization and biological evaluation of cationic porphyrin–terpyridine derivatives

Abstract

in the beta-pyrrolic positions; the results already obtained show that this type of PSs is also very promising.This fact, and our nding of an easy synthesis for porphyrin 1a (see Fig. 1) bearing a terpyridine unit in the beta pyrrolic position, 35 prompted us to expand the studies to the syntheses of the analogues 1b and 1c in order to use them as templates for further cationization. So, herein, we report the synthesis and the characterization of a series of neutral and cationic porphyrins bearing terpyridine units in one of their beta-pyrrolic positions. In the course of the characterization of these compounds we found that isomer differentiation of the cationic compounds could be easily achieved by ESI-MS (electrospray mass spectrometry).Additionally, their efficacy on the photoinactivation of bioluminescent E. coli was evaluated. The bioluminescent genetically transformed E. coli was selected as a model of Gramnegative bacteria to monitor in real-time photodynamic inactivation through bioluminescence measurement, thus avoiding the laborious and time-consuming conventional method of counting colony-forming units. Results and discussion Synthesis of neutral derivativesThe synthetic strategy to obtain the new b-pyrrolic cationic derivatives 6 and 7 (see Scheme 2) required the previous preparation of the corresponding neutral derivatives according with experimental work summarized in Scheme 1. The access to the new neutral porphyrins 1b and 1c bearing the terpyridine units in the b-pyrrolic positions involved the Kröhnke type approach described previously for the synthesis of porphyrin 1a. 35 In this methodology the terpyridine moiety was built directly from the easy accessible 2-formyl-5,10,15,20-porphyrin (TPP-CHO) 36 by reaction with 2-acetylpyridine (5 equiv.) in the presence of ammonium acetate (8 equiv.) and La(OTf) 3 (20 mol%).35 The procedure led to compound 1a in good yield (45%) affording as minor compounds the benzoporphyrin 2a (29%) and the porphyrin-chalcone 3a (10%) ( Table 1, entry 1).Based on that synthetic strategy we envisaged, just by changing the 2-acetylpyridine by the adequate 3-and 4-acetylpyridine the syntheses of the new neutral terpyridine derivatives 1b and 1c.In order to force the formation of the desired terpyridine 1a, the reaction was repeated in the presence of 2-acetylpyridine during 4 h. The results summarized in Table 1 (entry 2) show that the expected derivatives 1a, 2a and 3a were isolated in yields similar to our previously used conditions. However, a careful analysis of TLC data allowed us to detect a minor and more polar red product. Aer purication, the structure of this product, obtained in 4% yield, was established based on spectroscopic data (see infra and also ESI †) as the new 2-(2,4-diarylpyridin-6-yl)-5,10,15,20-tetraphenylporphyrin 4 (Fig. 2).Attempts to improve compound 4 yield by increasing the reaction time were not successful. The formation of the new derivative 4 can be explained in a similar manner as the one proposed for derivative 1a, 35 using as template...

Porphyrin-polymer nanocompartments: singlet oxygen generation and antimicrobial activity

“…In order to test the bio-functionality of the TPyCP-loaded polymersomes, we evaluated their ability to inhibit or prevent the growth of bacteria using a previously established protocol [ 48 ]. We determined the correlation between the colony-forming units (CFU) of E. coli and free TPyCP (200 μΜ in D 2 O) or TPyCP-loaded polymersomes (200 μM in D 2 O), respectively, upon irradiation and in dark conditions (Fig.…”

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

“…The Kröhnke-type approach was selected as the key step to obtain the cationic porphyrin-terpyridine derivatives 25 and 26 ( Scheme 8 ) [ 108 ]. The condensation of β-CHOTPP 3 with the adequate acetylpyridines afforded after a carefully selection of the experimental conditions the required neutral derivatives 22a , 22b and 22c as major products (yields between 45% to 48%) accompanied by the respective benzoporphyrins and porphyrin–chalcone-type derivatives.…”

“…The efficiency of these dicationic derivatives to photoinactivate the bioluminescent E. coli was evaluated and the results show that their efficacy was dependent on the PS concentration, singlet oxygen efficiency, charge localisation in the porphyrin core and light irradiance [ 108 ]. A reduction in bacterial bioluminescence, up to 5.4 log, was obtained with the most efficient photosensitizer 25a .…”

Laser-Induced Antibacterial Activity of Novel Symmetric Carbazole-Based Ethynylpyridine Photosensitizers

“… 9 Another effective way is to employ some cationic photosensitizers. 10 A pronounced cationic charge induced by a macromolecule with a large alkyl chain can bind to negatively-charged bacteria and alter the permeability of the outer membrane. 11 In the past decades, multiple kinds of photosensitizers including phthalocyanines, 12 chlorins, 13 porphyrins, 14 chlorophyll, 15 and bacteriochlorophyll 16 have displayed a fairly appreciable antimicrobial activity as photodynamic agents in the presence of oxygen because these derivatives generate potent oxygen species with suitable wavelengths.…”