On the Effect of Folic Acid-Derived Carbon Nanodots in Modulating the Noncanonical I-Motif DNA Structures

Noncanonical DNA segments are formed by those disobeying the Watson–Crick canon, and among which are the i-motifs. These are four-stranded DNA secondary structures that form sequences rich in cytosine (C). Two anti-parallely oriented DNA duplexes, held together by intercalated C:C + base pairs, are stabilized in the acidic pH under normal conditions. The i-motif structures have been observed forming and dissolving in living cells, and hence, this area is opened up for active investigation from the human cell perspective. DNA “breathing” is a thermally driven process, which interferes with the stability of the base-paired DNA sequences that transiently adopt local conformations, and the same is true for the i-motifs as well. Herein, we have synthesized folic acid (FA)-derived ultrasmall carbon nanodots (CNDs) with amine and amide surface functionalities that provide hydrogen-bonding centers. These CNDs interfere with the sequential breathing phenomenon and regulate the equilibrium in the i-motif formation. Thus, we could effectively regulate the transient process of the noncanonical i-motif production in real time, which, in turn, could be of great benefit in gene regulation and carcinogenic treatments.