title: Quantifying non-covalent binding affinity using mass spectrometry: a systematic study on complexes of cyclodextrins with alkali metal cations.
abstract: BACKGROUND
  To date, the quantification of binding affinities for non-covalent complexes between cyclodextrin (CD) and alkali cations including Li(+) , Na(+) , K(+) , Rb(+) , and Cs(+) has not been investigated in detail by electrospray ionization mass spectrometry (ESI-MS) due to the unknown ionization efficiencies of the different species. In this study, the binding constants of CD-Cs(+) complexes were determined by an improved mass spectrometric titration methodology, which was based only on the peak intensities of equilibrium CD. Hence, the discrepancy of ionization efficiencies of CD, alkaline cation and their complex would not affect the measurement. Then the obtained lgKa values were provided as references for competitive ESI-MS. The binding constants for complexes of α-, β- or γ-CD with Li(+) , Na(+) , K(+) and Rb(+) could be derived directly and quickly.
  
  
  METHODS
  The lgKa values between α-, β- or γ-CD and Cs(+) data were processed by curve fitting. These lgKa values were provided as references for competitive ESI-MS. In addition, linear fit equations for complexes of α-, β- or γ-CD with Cs(+) were derived. Through the linear fit equations of competitive ESI-MS, the binding constants for complexes of Li(+) , Na(+) , K(+) and Rb(+) with α-, β- or γ-CD were acquired.
  
  
  RESULTS
  Results showed that the binding constant (lgKa ) values for the complexes of Cs(+) with α-, β- and γ-cyclodextrins were 3.94, 3.88 and 3.80, respectively, revealing that the binding strength decreased with the increase in diameter of cyclodextrins. The competitive ESI-MS results showed a clear trend of decreasing affinity for complexes of cyclodextrins in the order of Li(+) , Na(+) , K(+) , Rb(+) .
  
  
  CONCLUSIONS
  The binding constants of non-covalent cyclodextrin-alkali cation complexes have been systematically studied by an improved mass spectrometric titration and competitive ESI-MS. Also, the structural features of the complexes were discussed. Our results are valuable for better understanding of mechanisms driving inclusion chemistry under well-defined conditions.
authors.affiliation: Laser Chemistry Institute, Chemistry Department, Fudan University, Shanghai, 200433, China.
authors.forename: Wanghui
authors.initials: W
authors.lastname: Wei
authors.affiliation: Physical Chemistry Institute, Chemistry Department, Fudan University, Shanghai, 200433, China.
authors.forename: Yanqiu
authors.initials: Y
authors.lastname: Chu
authors.affiliation: Department of Material Engineering, University of British Columbia, Canada.
authors.forename: Rizhi
authors.initials: R
authors.lastname: Wang
authors.affiliation: Physical Chemistry Institute, Chemistry Department, Fudan University, Shanghai, 200433, China.
authors.forename: Xiaodan
authors.initials: X
authors.lastname: He
authors.affiliation: Laser Chemistry Institute, Chemistry Department, Fudan University, Shanghai, 200433, China.
authors.forename: Chuanfan
authors.initials: C
authors.lastname: Ding
mesh_terms: D001665:Binding Sites; D002412:Cations / Q000737:chemistry; D003505:Cyclodextrins / Q000737:chemistry*; D008672:Metals, Alkali / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods
chemical_list: D002412:Cations; D003505:Cyclodextrins; D008672:Metals, Alkali