The non-covalent complexes of α- or γ-cyclodextrin with divalent metal cations determined by mass spectrometry

Noncovalent complexes between cyclodextrin (CD) and divalent metal cations drew growing attentions due to their applications in the pharmaceutical industry for molecular recognition. In this study, gas-phase binding of noncovalent complexes between α-, or γ-CD and divalent metal cations was investigated by electrospray ionization mass spectrometry (ESI-MS), demonstrating the formation of 1:1 stoichiometric noncovalent complexes. The binding of the complexes were furtherly confirmed by collision-induced dissociation (CID) with tandem mass spectrometry. The CID revealed the fragmentation pattern were strongly dependent on the electronic configuration of the cations and the charge separation reaction frequently took place in the cyclodextrin-complexes with transition metal cations. For the non-covalent complexes of α-CD with Mg2+, Ca2+, Sr2+ or Ba2+ at a collision energy of 25 eV, the fragments attributed to [α-CD + cation–nGlucose unit]2+ were observed (named series A). However, for the γ-CD complexes with transition metal cations Co2+, Ni2+, Cu2+ or Zn2+, apart from fragments of series A, it were observed fragment ions of [γ-CD + cation–nGlucose unit]+ (named series B), together with the Glucose unit (m/z 163.2) and its products with loss of H2O (m/z 145.2 and 126.8). The CID performed at a collision energy from 10 to 50 eV showed that the binding strength of complexes increase in the order of [α-CD + Mg]2+, [α-CD + Ca]2+, [α-CD + Sr]2+ and [α-CD + Ba]2+. Through mass spectrometric titrations, the values of dissociation constant Kd (in μmol•L−1) for the complexes of α-CD with Ca2+ or Ni2+ were obtained, which were 4.30 and 4.26, respectively. [Display omitted] •Fragment pattern for the complexes of cyclodextrin with alkaline-earth metals differed from transition metals.•The complexes of cyclodextrin with alkaline-earth metals were more stable with the increasing of radius of metals.•The complexes of cyclodextrin with dications occurred charge separation reaction when increasing declustering voltage.•Dissociation constant for the complexes of α-CD with Ca2+ or Ni2+ were obtained through mass spectrometric titrations.