M. Wainwright et al. / Journal of Photochemistry and Photobiology B: Biology 99 (2010) 74–77
77
Table 2
reportedly due to a considerably stronger binding interaction with
the nucleic acid [12]. Increased interaction with bacterial DNA
would support the increased photobactericidal activities exhibited
by the derivatives in the current work, compared with that of
methylene blue. Increased lipophilicity in the derivatives might
also explain the higher relative activity against E. coli, given the li-
pid-rich outer membrane associated with Gram-negative bacteria,
a multiple site of action hypothesis being currently favoured for
photoantimicrobials, as mentioned above.
While the number of compounds in the present study is not
great enough to produce robust structure–activity data, it may be
seen from the results of the antibacterial screen that greater pho-
tobactericidal activity was associated with derivatives where the
pendant aryl group contained a methoxyl group or halogen atom.
In addition, the noticeably increased activity of the 3-di-n-propyl
derivatives against E. coli relative to that against S. aureus supports
the increased outer membrane interaction of more hydrophobic
compounds (Figs. 2 and 3). It is intended that future work will ex-
plore greater functional and positional variation in benzyl ana-
logues, for example including those of a hydrophilic nature.
Bathochromic shifts for the derivatives caused by DNA intercalation.
kmax (nm) alone kmax (nm) + DNA Change
Methylene blue
665
652
650
653
654
645
658
656
656
658
658
669
666
662
665
665
659
670
669
666
669
668
660
+4
+14
+12
+14
+13
+14
+12
+13
+10
+11
+10
+12
1a
1b
1c
1d
1e
2a
2b
2c
2d
2e
1,9-Dimethyl methylene blue 648
As part of the current study, the binding of the photosensitisers
to DNA was measured to investigate possible binding changes
caused by molecular alteration in the phenothiazinium derivative.
All of the derivatives 1a–e and 2a–e demonstrated considerable
bathochromic shifts compared to the known intercalator, methy-
lene blue. The shifts observed for the derivatives were in the range
10–14 nm, compared to the 4 nm seen for the lead compound
(Table 2).
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The increases in absorption wavelength observed for the benzyl
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