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 K_d (in μmol•L^-1) for the complexes of α-CD with Ca²⁺ or Ni²⁺ were obtained, which were 4.30 and 4.26, respectively.