Cancer results in more fatalities annually than tuberculosis, HIV and malaria combined [1]. The conventional approaches to treatment tend to result in serious side effects. Photodynamic therapy (PDT) has provided a milder non-invasive approach for treating select cancers since the mid-1970s for tumors that can be irradiated with light from a fiber optic. After photoexcitation of a photosensitizer (PS) dye with an incident photon of appropriate wavelength, the T1 state is generated via intersystem crossing and cytotoxic singlet oxygen is formed from molecular dioxygen by energy transfer [2]. The first clinically approved PS dye was Photofrin®, a mixture of porphyrin oligomers. Issues faced with this dye include patients having to remain indoors for prolonged periods. Photofrin® has a near-forbidden lowest energy Q band at the edge of the phototherapeutic window (620–850 nm). There was a need to find better alternatives with intense absorption deep within this spectral region, since heme and other endogenous chromophores absorb at <600 nm [3], and H2O absorbs at >850 nm in the near-infrared (NIR).

Phthalocyanines with intense Q bands that lie between 650−700 nm were studied extensively as a second generation of PS dyes [4], but aggregation-related solubility issues were encountered due to π–π stacking. This makes their photophysical properties less favorable in the context of PDT. Structural modifications can be introduced to the structures of PS dyes to hinder aggregation and enhance their singlet oxygen quantum yield (ΦΔ) values. For similar reasons, chlorins (Scheme 1), including Purlytin® and chlorin e6 [5], [6], [7], which are porphyrin analogues with a reduced peripheral pyrrole bond, have also emerged as PS dyes in the context of PDT since they have a relatively intense lowest energy Q bands at ca. 650 nm [3,8,9].

In recent years, we have studied the PDT activities of the Sn(IV) complexes of high symmetry porphyrin analogues that can be readily synthesized, such as corroles [10,11], chlorins [12], [13], [14], [15], and N-confused porphyrins [16,17] to determine whether there is scope for developing new families of photosensitizer drugs that address issues faced with the second generation of dyes used for PDT. The trans-axial ligation provided by the Sn(IV) ion and the incorporation of functionalized meso‑aryl rings limits π-π stacking and decreases aggregation. The heavy atom effect of the Sn(IV) ion also results in higher ΦΔ values. In this study, the PDT activities of a series of structurally analogous porphyrin, chlorin and N-confused porphyrin dyes with 4‑methoxy‑meso-aryl rings (1-Por, 1-Chl and 1-NCP) and their Sn(IV) complexes (1-SnPor, 1-SnChl and 1-SnNCP) are directly compared (Scheme 1). The suitability of these dyes for use in photodynamic antimicrobial chemotherapy (PACT) as a possible alternative treatment in the context of resistance to antibiotics [18], [19], [20] is also examined against planktonic Staphylococcus aureus and Escherichia coli bacteria as typical Gram-(+) and -(−) strains, respectively. Unusually for non-cationic species [21,22], high Log10 reduction values were reported against E. coli in our previous studies with Sn(IV) chlorins with meso‑aryl substituents that contain sulfur atoms such as thienyl and methylthiophenyl groups [13,14]. This study investigates what happens when the sulfur atoms are replaced with oxygens across a series of three structurally related Sn(IV) porphyrinoid complexes.