Chemistry Reference
In-Depth Information
the TTAA region becomes narrower than in A-T alternate sequence and hence is
expected to provide a more suitable pocket for H
2
TMPyP4 binding than the minor
groove [
84
]. The external, groove binding is “end on” for the most part and causes
some disruption of the A-T hydrogen bonding pattern. If the steric features of the
porphyrin are such as to prevent close contact with the minor groove of DNA, the
A-T specificity is relaxed [
30
] and the binding becomes almost entirely based on
electrostatic interactions (“territorial” binding).
Issues regarding the aggregation state of DNA-bound porphyrins have interested
investigators almost from the very beginning. A very early report indicated that,
when added to DNA under high drug load conditions, H
2
TMAP aggregates on the
DNA surface [
85
]. The induced circular dichroism signal under these conditions is
bisignate and conservative. Although the magnitude of the features is not much
different from those for monomeric porphyrins, it was thought that this complex
involved an extended array of porphyrins. However, other evidence (circular
dichroism and RLS) suggests that these aggregates probably are more modest in
size. Similar results were obtained for NiTMPyP4 with poly(dA-dT) [
24
], but once
again, it is likely that aggregation is limited, in contrast to the extended assemblies
described below. In studies of DNA-bound
trans
-H
2
Pagg, induced circular dichro-
ism signals of an unusual shape and size are observed [
39
,
42
,
86
]. The signals
are bisignate, markedly nonsymmetric, and from one to two orders of magnitude
larger than for bound H
2
TMPyP4 or H
2
TMAP; values of
~10
3
M
1
cm
1
are
observed. The shape and especially the size of the CD signals could be best
accounted for in terms of an extended, electronically coupled, organized array of
porphyrin molecules [
87
]. The shape of CD signal of aggregated porphyrin
(H
2
TMPyP4) on polynucleotides was used by Kim to recognize the alternating
and non-alternating arrangement of DNA bases. In particular as the population of
the porphyrin increases (i.e., high porphyrin/DNA ratio), stacking interaction between
porphyrins becomes dominant and this interaction is strong enough to move the
porphyrins bound to the groove or intercalated, changing the binding mode; in fact,
a bisignate CD signal appears. The sign of excitonic CD depends on the order of the
DNA bases; the CD spectra of H
2
TMPyP complexed with non-alternating homopol-
ymer poly(dA) · poly(dT) or poly(dG) · poly(dC) are characterized by a positive band
at short wavelengths followed by a negative band at long wavelengths. In contrast,
those complexed with alternating polynucleotide poly(dA-dT) or poly(dG-dC) were
opposite to those of non-alternating homopolymers (Fig.
7
). Hence, they concluded
the signs of excitonic CD depend on the arrangement of the DNA bases, not on the
nature of them [
88
].
In addition to the metal-free derivative,
trans
-CuPagg was also found to produce
large induced CD signals. However, under similar conditions, the concentration of
salt required to induce
trans
-CuPagg aggregation is higher than that required for the
self-assembly of the naked
trans
-H
2
Pagg [
40
]. This is in contrast to
trans
-AuPagg
which gives induced CD patterns similar to those for CuTMPyP4 or other mono-
meric four-coordinate metalloporphyrin intercalators on binding to DNA [
40
].
Furthermore, the extent of aggregation of
trans
-H
2
Pagg and
trans
-CuPagg depends
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