Guanidino-aryl derivatives: protonation and structure tuning for spectrophotometric recognition of ds-DNA and ds-RNA

A series of aryl-substituted guanidines revealed a pKa of about 10 in aqueous medium, thus positioning themselves between the more basic aliphatic guanidines (pKa > 13) and the acidic guanidinocarbonyl-pyrrole (pKa 6). The study revealed that for the biorelevant (micromolar) affinity toward ds-DNA and ds-RNA, the minimal size of the aryl-unit is anthracene. Further aryl-increase (pyrene, porphyrin) did not result in a stronger affinity toward ds-DNA/RNA, nor give significant thermal stabilisation of the DNA/RNA double helix, thus suggesting that aromatic stacking interactions between the compounds and DNA/RNA are not the dominant binding interaction. Generally, the results suggested that aryl-guanidines bind to DNA/RNA grooves by a combination of hydrophobic, electrostatic, H-bonding and van der Waals interactions, whereby fluorescence of the two largest aromatics (pyrene, porphyrin) was highly sensitive in the fine probing of the DNA/RNA groove properties. In addition, pyrene and porphyrin analogues at excess polynucleotide binding sites aggregated within the polynucleotide groove, yielding fine recognition between various ds-DNA and ds-RNA by induced circular dichroism signals.