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

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.

A minimal i-motif stabilized by minor groove G:T:G:T tetrads

“…Since i-motif formation requires protonation of cytosines (19), these structures are more stable at acidic pH, although they can also be detected at nearly neutral pH. I-motif structures can also be stabilized by external agents, such as molecular crowding agents (20), single-walled carbon nanotubes (21), or site-specific incorporation of porphyrin moieties (22). Several i-motif structures have been found in oligonucleotides from centromeric (23,24) and telomeric (25) repetitive sequences.…”

“Click”-reaction: An alternative tool for new architectures of porphyrin based derivatives

“…This reaction has been applied in many tetrapyrrolic entities such as porphyrins [55], phthalocyanines [55] and more recently corroles [56,57]. Concerning the applications of click-made porphyrins many studies have been made on photodynamic therapy (PDT) [58][59][60][61], polymers [62][63][64][65], self-assembly [66][67][68], biochemistry [69][70][71][72] and materials chemistry [73][74][75][76]. The scope of this work is to present click reactions that are carried out on porphyrin compounds.…”

Nanoarchitectonics with Porphyrin Functionalized DNA

“…45 The use of metalated porphyrins is crucial to avoid copper metalation during the coupling; most conveniently zinc is used, which is subsequently lost in the DNA synthesis, yielding the free-base porphyrin–DNA. As alternative methods, amide coupling, 46 click chemistry 47 or maleimide–thiol conjugation 48 can equally well be used. Structurally different modifiers such as diphenyl porphyrin (DPP-dU), tetraphenyl porphyrin (TPP-dU), or propargylamide-linked TPP (TPPA-dU) were thus synthesized (Figure 6a) Phosphitylation is straightforward, though the phosphoramidites are highly susceptible to oxidation due to the photosensitizing activity of the porphyrin.…”