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Lewis acid catalyzed condensation of pyrrole and 4-fluoro-2,6-dimethylbenzaldehyde followed by chemical oxidation afforded the corresponding chlorin along with the parent porphyrin. The subsequent metalation of the porphyrin-chlorin mixture in the presence of Zn(OAc)₂•2H₂O afforded Zn monoand di-hydroxychlorins in addition to the Zn porphyrin in a one-flask synthesis. This new direct hydroxylation reaction eliminates the need for highly toxic OsO₄and H₂S that are traditionally used for the generation of hydroxy chlorins. In addition to the full characterization of the zinc chlorins, we present cyclic voltammograms, steady-state absorption, and emission profiles of this rarely available class of compounds. Our findings show that Zn mono- and di-hydroxychlorins are stable compounds that possess exceptionally long triplet excited states in solution, making them promising candidates for photodynamic therapy. 

Lysosomes play important roles in catabolism, nutrient sensing, metabolic signaling, and homeostasis. NPC1 deficiency disrupts lysosomal function by inducing cholesterol accumulation that leads to early neurodegeneration in Niemann-Pick type C (NPC) disease. Mitochondria pathology and deficits in NPC1 deficient cells are associated with impaired lysosomal proteolysis and metabolic signaling. It is thought that activation of the transcription factor TFEB, an inducer of lysosome biogenesis, restores lysosomal-autophagy activity in lysosomal storage disorders. Here, we investigated the effect of trehalose, a TFEB activator, in the mitochondria pathology of NPC1 mutant fibroblastsin vitroand in mouse developmental Purkinje cellsex vivo. We found that in NPC1 mutant fibroblasts, serum starvation or/and trehalose treatment, both activators of TFEB, reversed mitochondria fragmentation to a more tubular mitochondrion. Trehalose treatment also decreased the accumulation of Filipin⁺cholesterol in NPC1 mutant fibroblasts. However, trehalose treatment in cerebellar organotypic slices (COSCs) from wild-type andNpc1^nmf164mice caused mitochondria fragmentation and lack of dendritic growth and degeneration in developmental Purkinje cells. Our data suggest, that although trehalose successfully restores mitochondria length and decreases cholesterol accumulation in NPC1 mutant fibroblasts, in COSCs, Purkinje cells mitochondria and dendritic growth are negatively affected possibly through the overactivation of the TFEB-lysosomal-autophagy pathway.