A novel type of organometallic 2-R-2,4-dihydro-1 H -3,1-benzoxazine with R = [M(η 5 -C 5 H 4 )(CO) 3 ] (M = Re or Mn) units. Experimental and computational studies of the effect of substituent R on ring-chain tautomerism

The syntheses, characterization, X-ray crystal structures, electrochemical properties and anticancer and antichagasic activities of the first examples of 2-substituted 2,4-dihydro-1 H -3,1-benzoxazines with half-sandwich organometallic arrays, [M(η 5 -C 5 H 4 )(CO) 3 ] (M = Re or Mn), at position-2 are described. Experimental and computational studies based on DFT calculations on the open forms [Schiff bases of general formulae R-CHN-C 6 H 4 -2-CH 2 OH] ( 5 ), with R = ferrocenyl ( a ), phenyl ( b ), cyrhetrenyl ( c ) or cymantrenyl ( d ), and their tautomeric forms (2-substituted 2,4-dihydro-1 H -3,1 benzoxazines) have allowed us to establish the influence of substituents a–d and solvents on: (a) the extent of tautomeric equilibria ( 5a–5d ) ↔ ( 6a–6d ) and (b) their electrochemical properties and the electronic distribution on the open and closed forms. Despite the formal similarity between 6c and 6d , their anticancer and antiparasitic activities are markedly different. Compound 6d is inactive in the HCT116, MDA-MB231 and MCF7 cancer cell lines, but 6c shows moderate activity in the latter cell line, while the Mn( i ) complex ( 6d ) is a more potent anti- Trypanosoma cruzi agent than its Re( i ) analogue ( 6c ).