Mono- and tetra-substituted zinc(II) phthalocyanines containing morpholinyl moieties: Synthesis, antifungal photodynamic activities, and structure-activity relationships

• A series of ZnPcs substituted with morpholineyl moieties have been synthesized.
• The structure-activity relationships of these compounds have been discussed.
• The cellular uptake and photocytotoxicity increased after quaternization.
• The cationic ZnPc 6a shows the highest photocytotoxicity against C. albicans.

A series of zinc(II) phthalocyanines (ZnPcs) mono-substituted and tetra-substituted with morpholinyl moieties and their quaternized derivatives have been synthesized and evaluated for their antifungal photodynamic activities toward Candida albicans. The α-substituted, quaternized, and mono-substituted ZnPcs are found to have higher antifungal photoactivity than β-substituted, neutral, and tetra-substituted counterparts. The cationic α-mono-substituted ZnPc (6a) exhibits the highest photocytotoxicity. Moreover, it is more potent than axially di-substituted analogue. The different photocytotoxicities of these compounds have also been rationalized by investigating their spectroscopic and photochemical properties, aggregation trend, partition coefficients, and cellular uptake. The IC90 value of 6a against C. albicans cells is as low as 3.3 μM with a light dose of 27 J cm−2, meaning that 6a is a promising candidate as the antifungal photosensitizer for future investigations.

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