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Here, guanine\u2010rich nucleic acid binding of a water\u2010soluble cationic, regiopure <jats:italic>C<\/jats:italic><jats:sub>4h<\/jats:sub> zinc phthalocyanine bearing four triethylene glycol methyl ether and four <jats:italic>N<\/jats:italic>\u2010methyl\u20104\u2010pyridinium substituents (<jats:bold>1<\/jats:bold>) is reported. In contrast to double\u2010stranded DNA, guanine systems <jats:bold>GpG<\/jats:bold>, <jats:bold>(GG)<jats:sub>10<\/jats:sub><\/jats:bold>, <jats:bold>poly(G)<\/jats:bold> and <jats:bold>quadruplex DNA<\/jats:bold> are shown to effectively disrupt phthalocyanine aggregates in buffered solution. This process is accompanied by evolution of the Q\u2010band absorbance and enhanced emission. Increasing the sequence length from <jats:bold>GpG<\/jats:bold> to <jats:bold>(GG)<jats:sub>10<\/jats:sub><\/jats:bold> increases the binding and confirms the importance of multiple binding interactions. Enhanced binding in the presence of KCl suggests the importance of nucleobase hydrogen\u2010bonded mosaics in phthalocyanine binding. Notably, the <jats:bold>(GT)<jats:sub>10<\/jats:sub><\/jats:bold> sequence is even more effective than quadruplex and pure guanine systems at disrupting the aggregates of <jats:bold>1<\/jats:bold>. Significant time\u2010dependent binding of <jats:bold>1<\/jats:bold> with <jats:bold>poly(G)<\/jats:bold> reveals biexponential binding over minutes and hours, which is linked to local conformations of <jats:bold>poly(G)<\/jats:bold> that accommodate monomers of <jats:bold>1<\/jats:bold> over time. The study highlights the ability of biomacromolecules to disrupt phthalocyanines aggregates over time, which is an important consideration when rationalizing photoactivity of photosensitizers in\u2010vivo.<\/jats:p>","DOI":"10.1002\/chem.202403095","type":"journal-article","created":{"date-parts":[[2024,11,29]],"date-time":"2024-11-29T13:59:05Z","timestamp":1732888745000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Role of Secondary Structure and Time\u2010Dependent Binding on Disruption of Phthalocyanine Aggregates by Guanine\u2010Rich Nucleic Acids"],"prefix":"10.1002","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7795-3959","authenticated-orcid":false,"given":"Eleanor R.","family":"Windle","sequence":"first","affiliation":[{"name":"School of Chemistry University College Dublin  Belfield, Dublin 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