A series of meso-tris (N-methyl-pyridiniumyl)-(4-alkylamidophenyl) porphyrins: synthesis, interaction with DNA and antibacterial activity.
A series of meso-5,10,15-tris(N-methyl-4-pyridiniumyl)-20-(4-alkylamidophen yl) porphyrins were synthesized by derivatizing the amino group on the phenyl ring with the following hydrophobic groups: -C(O)C7F15, -C(O)CH=CH2, C(O)CH3, -C(O)C7H15, and -C(O)C15H31. The cationic tris-pyridiumyl porphyrin core serves as a DNA binding motif and a photosensitizer to photomodify DNA molecules. The changes of the UV-Vis absorption spectra during the titration of these porphyrins with calf thymus DNA revealed a large bathochromic shift (up to 14 nm) and a hypochromicity (up to 55%) of the porphyrins Soret bands, usually considered as proof of porphyrin intercalation into DNA. Association constants (K) calculated according to the McGhee and von Hippel model, were in the range of 10(6)-10(7) M(-1). An increase in hydrophobicity of the substituents at the 20-meso-position produced higher binding affinity. These porphyrins caused photomodification of the supercoiled plasmid DNA when a green laser beam at 532 nm was applied. Those with higher surface activity acted more efficiently as DNA photomodifiers. The porphyrin with a perfluorinated alkyl chain (-COC7F15) at the meso-20-position inhibited the growth of gram-positive bacteria (S. aureus, or S. epidermidis). Other porphyrins exhibited moderate activity against both gram-negative and gram-positive organisms.
Li
H
H
Department of Chemistry, University of Idaho, Moscow 83844, USA.
Fedorova
O S
OS
Grachev
A N
AN
Trumble
W R
WR
Bohach
G A
GA
Czuchajowski
L
L
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects*; D004247:DNA / Q000187:drug effects / Q000378:metabolism*; D004926:Escherichia coli / Q000187:drug effects; D007364:Intercalating Agents / Q000138:chemical synthesis*; D008652:Mesoporphyrins / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D017319:Photosensitizing Agents / Q000138:chemical synthesis; D011166:Porphyrins / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D013056:Spectrophotometry, Ultraviolet; D013211:Staphylococcus aureus / Q000187:drug effects; D013212:Staphylococcus epidermidis / Q000187:drug effects
D000900:Anti-Bacterial Agents; D007364:Intercalating Agents; D008652:Mesoporphyrins; D017319:Photosensitizing Agents; D011166:Porphyrins; D004247:DNA