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Abstract Mono‐ andbis‐decylated lumazines have been synthesized and characterized. Namely,mono‐decyl chain [1‐decylpteridine‐2,4(1,3H)‐dione]6aandbis‐decyl chain [1,3‐didecylpteridine‐2,4(1,3H)‐dione]7aconjugates were synthesized by nucleophilic substitution (S_N2) reactions of lumazine with 1‐iododecane inN,N‐dimethylformamide (DMF) solvent. Decyl chain coupling occurred at theN¹site and then theN³site in a sequential manner, without DMF condensation. Molecular orbital (MO) calculations show ap‐orbital atN¹but notN³, which along with a nucleophilicity parameter (N) analysis predict alkylation atN¹in lumazine. Only after the alkylation atN¹in6a, does ap‐orbital onN³emerge thereby reacting with a second equivalent of 1‐iododecane to reach the dialkylated product7a. Data from NMR (¹H,¹³C, HSQC, HMBC), HPLC, TLC, UV‐vis, fluorescence and density functional theory (DFT) provide evidence for the existence ofmono‐decyl chain6aandbis‐decyl chain7a. These results differ to pterinO‐alkylations (kinetic control), whereN‐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.