Session: Physical Organic Chemistry: Calculations, Mechanisms, Photochemistry & High-Energy Species:

Mono- and bis-decylated lumazines have been synthesized and characterized. Namely, mono-decyl chain [1-decylpteridine-2,4(1,3H)-dione] and bis-decyl chain [1,3-didecylpteridine-2,4(1,3H)-dione] conjugates were synthesized by nucleophilic substitution (S_N2) reactions of lumazine with 1-iododecane in N,N-dimethylformamide (DMF) solvent. Decyl chain coupling occurred at the N¹ site and then the N³ site in a sequential manner, without DMF condensation. Molecular orbital (MO) calculations show a p-orbital at N¹ but not N³, which along with a nucleophilicity parameter (N) analysis predict alkylation at N¹ in lumazine. Only after the alkylation at N¹ in 1-decylpteridine-2,4(1,3H)-dione, does a p-orbital on N³ emerge thereby reacting with a second equivalent of 1-iododecane to reach the dialkylated product [1,3-didecylpteridine-2,4(1,3H)-dione]. Data from NMR (¹H, ¹³C, HSQC, HMBC), HPLC, TLC, UV-vis, fluorescence, and density functional theory (DFT) provide evidence for the existence of mono-decyl chain 1-decylpteridine-2,4(1,3H)-dione and bis-decyl chain 1,3-didecylpteridine-2,4(1,3H)-dione. These results differ to pterin O-alkylations (kinetic control), where N-alkylation of lumazine is preferred and then to dialkylation (thermodynamic control), with an avoidance of DMF solvent condensation. These findings add to the list of alkylation strategies for increasing sensitizer lipophilicity for use in photodynamic therapy.

Edyta Greer

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