Porphyrins as spectroscopic sensors for conformational studies of DNA

Abstract

Molecular systems containing two or more interacting porphyrins show remarkable spectroscopic features that allow for a very sensitive detection of conformational changes on the microscale level by different methods, such as fluorescence and electronic circular dichroism (ECD). Covalent porphyrin-DNA assemblies can provide a CD profile (exciton couplet) within the porphyrin Soret band region which is very diagnostic for DNA conformational changes. Additionally, covalently linked porphyrins have been shown to function as DNA molecular caps and to stabilize the non-self-complementary non-Watson-Crick guanine-adenine DNA sequence via their strong π-π stacking.

Mechanistic aspects of the interaction of intercalating metal complexes with nucleic acids

“…The flat aromatic structure of porphyrins, both free and in form of metal complexes, coupled with their high absorptivity and intensity of fluorescence emission, make these substances specially suitable for investigations on the mechanisms of drug binding to nucleic acids. Actually, DNA/porphyrin systems have been analysed using different methods; among them we recall spectroscopy [40], viscometry [41], dialysis equilibria [42] and resonance light scattering (RLS), the latter being introduced by Pasternack and his school [43]. Kinetic investigations on the DNA-porphyrin interaction are rather scarce [19] and often confined to the analysis of drug dissociation induced by SDS [44].…”

Significantly Enhanced DNA Thermal Stability Resulting from Porphyrin H‐Aggregate Formation in the Minor Groove of the Duplex

“…[17,18] This provides structures that have porphyrin residues as 3'-or 5'-molecular caps, [12,[18][19][20] thus introducing them instead of a nucleobase in the middle of the helix [17] or as a label in the minor [10,16] and major [6][7][8] grooves. Recently, the synthesis of a DNA containing eleven meso-functionalized porphyrins attached to 5-ethynyl-2'-deoxyuridines was carried out from the corresponding phosphoramidites; however, this showed a significant thermal destabilization of the resulting duplex.…”

Synthesis of β‐Pyrrolic‐Modified Porphyrins and Their Incorporation into DNA

“…[3] The site-specific covalent attachment of porphyrin moieties to DNA has been achieved by using a variety of methodologies including the modification of nucleobases, [4][5][6][7][8][9] ribofuranose residues, [10][11][12][13][14][15] the phosphate backbone [16,17] and acyclic linkers. [18,19] Porphyrin moieties have been introduced as 3'-or 5'-molecular caps, [13,[19][20][21] as a nucleobase substituent in the middle of the helix [18] or as a label in the minor [11,17,22] and major [5][6][7][8][9] grooves. Several tethers have been used for the covalent attachment of porphyrins including maleimidothiols, [8,17] amides, [11][12][13]15] phosphates [16] and alkynes.…”

“…[18,19] Porphyrin moieties have been introduced as 3'-or 5'-molecular caps, [13,[19][20][21] as a nucleobase substituent in the middle of the helix [18] or as a label in the minor [11,17,22] and major [5][6][7][8][9] grooves. Several tethers have been used for the covalent attachment of porphyrins including maleimidothiols, [8,17] amides, [11][12][13]15] phosphates [16] and alkynes. [4][5][6][7]9] The incorporation of the porphyrins as 5 and 3 caps has been shown to improve base-pair fidelity and duplex stability [10] as well as showing the ability for the porphyrins to electronically communicate with each other (exciton coupling).…”

“…This feature enables porphyrins to be used as detectors of DNA secondary structures in circular dichroism (CD) spectroscopy. [12][13][14][15][16]21] The internal modification of ONs with porphyrins has recently become of interest for the development of helical scaffolds. Such examples include the synthesis of a DNA containing 11 meso-functionalised porphyrins on a single strand [5,6] and a zipper porphyrin assembly in the major groove of a DNA duplex.…”