Regioselectivity for condensation reactions of quinonoid models of tryptophan tryptophylquinone: a density functional theory study.

ABSTRACT

The model compounds of tryptophan tryptophylquinone (TTQ), o-benzoquinone (OBQ), 3-methyl-6,7-dihydro-1H-6,7-indoledione (MIQ), and 3-methyl-4-(3-methyl-1H-2-indolyl)-6,7-dihydro-1H-6,7-indoledione (IIQ), all of which are characteristic of o-quinone groups, have been studied with density functional theory. The dihedral angle of the two indole rings (chi) of IIQ is calculated to be 49.6 degrees for the global minimum. Another local minimum, 0.74 kcal/mol higher in energy, with a chi value of 123.5 degrees is also fully optimized. The transition state connecting the two minima, with a chi value of 97.9 degrees, has been located and the rotation barrier is 1.71 kcal/mol. A scan of the potential energy surface along this dihedral angle showed that the difference of the total energy was within 1.0 kcal/mol at a range of the dihedral angle from 30 degrees to 75 degrees. Hence, IIQ is flexible for the rotation of inter-indole rings. The origin of regioselectivity for the condensation reactions of the models MIQ and IIQ with NH(3) has been elucidated. It is shown that the energy difference between the two different types of carbinolamine intermediates (Delta E) and their corresponding transition structures (Delta E(++)) should be responsible for the regioselectivity. To assess the effect of the fused ring on regioselectivity of the condensation reaction, a series of models were designed. A good linear correlation has been found between the energy difference of the two different carbinolamine intermediates (Delta E) and that of the corresponding transition states (Delta E(++)), suggesting that the factors that stabilize the carbinolamine intermediate also favor the stability of the corresponding transition structure. The pair, 6-amino-6-hydroxy-8-methyl-6H-quinolin-5-one and 5-amino-5-hydroxy-8-methyl-5H-quinolin-6-one (7/8), deviates from the correlation and represents some anomalous behavior, which may be due to their structural particularity. It also has been shown that the tricyclic models, which consist of OBQ and two fused heterocyclic rings, represent more regioselectivity in contrast to the bicyclic systems. Moreover, the fused electron-donating pyrrole and the fused electron-withdrawing pyridine or pyrimidine show a somewhat synergistic effect on each other via the medial OBQ molecule. The barrier of the condensation reaction for pyrrolo[2,3-f]quinoline-4,5-dione is calculated to be ca. 22 kcal/mol. This is lower than that for MIQ (ca. 33 kcal/mol) and IIQ (ca. 32 kcal/mol) by as much as 10.0 kcal/mol, explaining reasonably the larger catalytic effect of pyrroloquinolinequinone (PQQ) relative to TTQ.