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Synthesis of β‐Pyrrolic‐Modified Porphyrins and Their Incorporation into DNA
Author(s) -
Stephenson Adam W. I.,
Partridge Ashton C.,
Filichev Vyacheslav V.
Publication year - 2011
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201003200
Subject(s) - porphyrin , sonogashira coupling , oligonucleotide , chemistry , dna , cycloaddition , pyrimidine , covalent bond , intercalation (chemistry) , stereochemistry , chromophore , combinatorial chemistry , linker , photochemistry , palladium , organic chemistry , biochemistry , catalysis , computer science , operating system
Abstract A synthetic methodology for the synthesis of various β‐pyrrolic‐functionalised porphyrins and their covalent attachment to 2′‐deoxyuridine and DNA is described. Palladium(0)‐catalysed Sonogashira and copper(I)‐catalysed Huisgen 1,3‐dipolar cycloaddition reactions were used to insert porphyrins into the structure of 2′‐deoxyuridine and DNA. Insertion of a porphyrin into the middle of single‐stranded CT oligonucleotides possessing a 5′‐terminal run of four cytosines was shown to trigger the formation of pH‐ and temperature‐dependent i‐motif structures. Porphyrin insertion also led to the aggregation of single‐stranded purine–pyrimidine sequences, which could be dissociated by heating at 90 °C for 5 min. Parallel triplexes and anti‐parallel duplexes were formed in the presence of the appropriate complementary strand(s). Depending on the modification, porphyrins were placed in the major and minor grooves of duplexes and were used as bulged intercalating insertions in duplexes and triplexes. In general, the thermal stabilisation of parallel triplexes possessing porphyrin‐modified triplex‐forming oligonucleotide (TFO) strands was observed, whereas anti‐parallel duplexes were destabilised. These results are compared and discussed on the basis of the results of molecular modelling calculations.