DNA i-Motifs Reversibly Disperse and Modulate the Photophysical Properties of an Aggregated Zinc Phthalocyanine Photosensitizer, Triggered by pH and Temperature.

Cytosine-rich DNA i-motifs (iM) efficiently and reversibly disperse aggregated cationic zinc phthalocyanine (Pc) photosensitizer 1 into a monomeric DNA-bound form with turned-on near-infrared emission and singlet oxygen (1O2) photosensitization. Aggregate disruption and binding occur exclusively with folded iMs, enabling pH- and temperature-controlled switching of Pc photophysics. Circular dichroism (CD) titrations and thermal denaturation studies with biologically relevant iMs, including those formed from the human telomere and cMYC oncogene promoter sequences, reveal sequence-dependent dispersion efficiency. Several folded iMs rival G-quadruplex DNA in disrupting Pc aggregates, while unfolded iMs and duplex DNA are ineffective. Spectroscopic and thermal analyses indicate that binding is favored by structural flexibility and partially folded states. Importantly, iM-mediated dispersion switches on reversible 1O2 photosensitization under acidic conditions. These findings identify DNA iMs as potent and previously unrecognized regulators of Pc photosensitizer aggregation, providing a potential DNA-gated responsive strategy for modulating their photodynamic versus photothermal activity.