Molecular dynamics simulations of nitrate complexes with polyammonium macrocycles: Insight on phosphoryl transfer catalysis

Nitrate complexes of two different polyammonium macrocycles, the tetrahydrogen nitrate salts of 1,4,7, 16,19,21-hexaaza-10,13-dioxacyclotetraco [24]N6O2 . 4HNO(3), 1, and 1,4,10,13-tetraaza-7,16-dioxacyclooctade [18]N4O2 . 4HNO(3), 2, have been isolated and their structures determined by X-ray crystallographic methods. Compound 1 crystallizes in the orthorhombic space group Imma with unit cell dimensions a = 22.692(3) Angstrom, b = 19.563(3) Angstrom, c = 7.005(1) Angstrom, V = 3110(1) Angstrom(3), and Z = 4. Compound 2 crystallizes in the orthorhombic space group Pbca with a = 13.877(1) Angstrom, b = 15.553(1) Angstrom, c 10.742(1) Angstrom, V = 2314.6(5) Angstrom(3), and Z = 8. Full-matrix least-squares refinement resulted in R = 0.051 and R(w) = 0.067 for 1 and R = 0.063 and R(w) = 0.072 for 2. Compound 1 has a boat-shaped geometry, and one of the four nitrates is situated in the macrocyclic cavity. Compound 2 is relatively flat with two nitrates above and two below the plane of the molecule. Molecular dynamics simulations were performed for the two molecules using the structural coordinates obtained from the crystal structures and the CHARMM molecular model. Simulations were carried out to 400 ps for 1 and 200 ps for 2 using 2 fs time steps. The average temperature during the simulation was 302 +/- 5 K and the average total energy was -7805.9 +/- 0.5 kcal mol(-1) for 1 and -7851.9 +/- 0.5 kcal mol(-1) for 2. The conformation of 2 did not change appreciably during the simulations, whereas 1 flattened out considerably due to hydration effects.