Efficient determination and evaluation of model cyclodextrin complex binding constants by electrospray mass spectrometry

Abstract

Electrospray ionization mass spectrometry (ESI-MS) is now routinely used for the detection of cyclodextrin noncovalent complexes, complementing previously established methods. Hostguest complexes formed in solution are also stable for characterization by ESI in the gas phase. This paper reports the first investigations to characterize the stability of three inclusion complexes between ␤-cyclodextrin (␤-CD) and three model "guest" molecules, by determining the cyclodextrin compound complex stability constant (K st ) with the use of mass spectrometric studies. The relative signal intensity of the complexes were monitored in the positive ion mode by mixing each "guest" molecule with an up to 50-fold molar excess of ␤CD. A novel linear equation, similar to Benesi-Hildebrand, was derived allowing the determination of K st for 1:1 stoichiometry in all complexes. These values were compared with the K st obtained by spectrophotometric experiments and they were evaluated to be slightly different, indicating the validity of the described method. (J

Monitoring of complex forming of the active pharmaceutical substance and β-cyclodextrin as an additive of the mobile phase using mass spectrometry

“…Prilikom stvaranja kompleksa sa β-CD manje polarni deo molekule "gosta" se uvlači u šupljinu, dok su polarnije grupe u kontaktu sa polarnim rastvaračem (8). Tako, fenil grupe molekule "gosta" kao hidrofobne lako se uklapaju u šupljinu β-CD, a amino, alkoholne, fenolne i karbonilne grupe omogućavaju interakcije sa hidrofilnim grupama na spoljašnjoj površini β-CD formiranjem vodoničnih veza, omogućavajući na taj način dodatnu stabilizaciju nagrađenog kompleksa (9). Uklapanje molekula u šupljinu β-CD, odnosno komplementarnost između njihovih veličina, određuje stabilnost kompleksa i selektivnost procesa kompleksiranja (10,11).…”

“…Uklapanje molekula u šupljinu β-CD, odnosno komplementarnost između njihovih veličina, određuje stabilnost kompleksa i selektivnost procesa kompleksiranja (10,11). β-CD i molekul "gost" mogu da formiraju komplekse u različitim odnosima (9).…”

Measurement of Inclusion Complex Formation between Cyclophane and Biological Relevant Amino Acids Using Electrospray Ionization, Cold-Spray Ionization and Fast Atom Bombardment Mass Spectrometry

“…After 24 h, the reaction mixture was filtered. The filtrate was extracted with EtOAc (50 mlϫ3), washed with brine and dried over MgSO 4 . After removal of the solvent under reduced pressure, the residue was purified by column chromatography on silica gel with EtOAc : CHCl 3 (1 : 9) as an eluent to give 1.6 g, 93% as a colorless solid.…”

“…Recently, it reported that mass spectrometry can be used to detect noncovalent association complexes. [1][2][3][4] We reported that FAB-MS is useful method as well as 1 H-NMR method not only for confirmation of TGDMAP (1) and biological relevant phosphates such as nucleotide complex geometry but also for determination of stability constant (K s ) values of the complexes because the K s value calculated by FAB-MS (100 M Ϫ1 for UMP) was most similar to the K s value calculated by 1 H-NMR spectrometry (110 M Ϫ1 for UMP). …”

Investigation of monovalent and bivalent enantioselective molecular recognition by electrospray ionization-mass spectrometry and tandem mass spectrometry

“…The cited review articles indicate a wealth of applications in the areas of protein (enzyme)-ligand and oligonucleotide (RNA, DNA)-ligand interaction systems. With respect to small molecule [37][38][39][40][41][42][43][44] and chiral recognition systems [25,26,28,[45][46][47][48], far fewer quantitative solutionphase affinity studies have been reported utilizing ESI-MS. The majority of work relating the application of mass spectrometry to studying enantioselective interactions has centered on gas-phase tandem mass spectrometric (e.g., by ion/molecule reactions and the kinetic method) or desorption mass spectrometric (e.g., by fast atom bombardment) experiments [49 -58].…”