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NMR and Computational Study of N7/N9 Transacylation in Ferrocenoyl-Purines

Organometallic derivatives of nucleobases have attracted substantial attention in the field of synthetic organic chemistry. Nucleosides in which sugar part is replaced with organometalic moiety, such as ferrocene, combine electro- and bio-active fragments and are shown to exhibit anticancer and antibacterial activity.[1] We have prepared a series of N-ferrocenoylated C6-substitued purines with carbonyl group as a linker [2] between the two parts. In the course of reaction two isomers were formed, isolated and assigned to N7 and N9, with the ratio dependent on substituents of the purine ring. However, in common polar organic solvents, e.g. DMSO and DMF, at room temperature, N7/N9 transacylation occurs and the two isomers exist in dynamic equilibrium. Combining the experimental (NMR) and theoretical (DFT) study, we were able to determine the mechanism of N7/N9 transacylation. We found that this is a common process in acylated (non-organometallic) purines. The transacylation reaction in purines starts with the nucleophilic addition of DMSO to the carbonyl group at the N7-position and follows the SN2-like mechanism (Figure 1.). Gibbs free energy barriers calculated at the B3LYP/6-31G(d)/SDD and M06L/6-311+G(d, p)/SDD level agree well with experimental (ΔG ≈100 kJ/mol) data and support the proposed transacylation mechanism (Figure 1.).

N-ferrocenoylated C6-substitued purines , N7/N9 transacylation, DFT calculations, NMR study

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