The conformation of biliverdin in dimethyl sulfoxide: implications for the coordination with copper

Biliverdin (BV) structure was analyzed by using NMR techniques and unrestricted density function theory simulations to explainthe incapacity of BV to build coordination complex(es) with Cu2+in dimethyl sulfoxide, which was confirmed by UV-Vis, EPRand NMR spectroscopy. NMR showed that N atoms are protonated in all four pyrrole rings. The structure is stabilized by twohydrogen bonds between NH moieties and carbonyl oxygens from opposite terminal pyrrole rings, and by the bending ofpropionyl chain with carboxyl group out of the plain toward central position of BV. The simulations of deprotonated BV, whichbuilds copper complexes in water and chloroform as described previously, showed a different conformation and organization ofhydrogen bonds. Taking into account that deprotonation represents a critical step in coordinate bonds formation, the protonationof an additional N atom may represent a key difference between the interactions of BV with copper in different solvents.