title: Simple chip-based interfaces for on-line monitoring of supramolecular interactions by nano-ESI MS.
abstract: Two simple interfaces were designed and realized, enabling on-line coupling of microfluidics reactor chips to a nanoflow electrospray ionization (NESI) time-of-flight (TOF) mass spectrometer (MS). The interfaces are based on two different approaches: a monolithically integrated design, in which ionization is assisted by on-chip gas nebulization, and a modular approach implying the use of commercially available Picospray tips. Using reserpine as a reference compound in a 1ratio1 mixture of acetonitrile and water revealed that both interfaces provide a remarkably stable mass spectrometric signal (standard deviations lower than 8% and 1% for the monolithic and modular approaches, respectively). Glass microreactors, containing mixing zones, were fabricated and coupled to the modular interface with perfluoroelastomer Nanoport fluidics connectors, providing a tool to study chemical reactions on-line. Investigation of the mixing dynamics showed that complete on-chip reagents mixing is achieved within a few tens of milliseconds. Metal-ligand interactions of Zn-porphyrin with pyridine (2), 4-ethylpyridine (3), 4-phenylpyridine (4), N-methylimidazole (5), and N-butylimidazole (6) in acetonitrile as well as host-guest complexations of beta-cyclodextrin (7) with N-(1-adamantyl)acetamide (8) or 4-tert-butylacetanilide (9) in water were studied by mass spectrometry using the modular NESI-chip interface. From on-chip dilution-based mass spectrometric titrations of Zn-porphyrin 1 with pyridine (2) or 4-phenylpyridine (4) in acetonitrile Ka-values of 4.6 +/- 0.4 x 10(3) M(-1) and 6.5 +/- 1.2 x 10(3) M(-1), respectively, were calculated. The Ka-values are about four times larger than those obtained with UV/vis spectroscopy in solution, probably due to a higher ionization efficiency of complexed compared to uncomplexed Zn-porphyrin. For the complexation of N-(1-adamantyl)acetamide (8) with beta-cyclodextrin (7), a Ka-value of 3.6 +/- 0.3 x 10(4) M(-1) was obtained, which is in good agreement with that determined by microcalorimetry.
authors.affiliation: Laboratory of Supramolecular Chemistry and Technology, MESA+ Institute for Nanotechnology, University of Twente, P. O. Box 217, 7500 AE, Enschede, The Netherlands.
authors.forename: Monica
authors.initials: M
authors.lastname: Brivio
authors.forename: R Edwin
authors.initials: RE
authors.lastname: Oosterbroek
authors.forename: Willem
authors.initials: W
authors.lastname: Verboom
authors.forename: Albert
authors.initials: A
authors.lastname: van den Berg
authors.forename: David N
authors.initials: DN
authors.lastname: Reinhoudt
mesh_terms: D000083:Acetanilides / Q000737:chemistry; D000097:Acetonitriles / Q000737:chemistry; D000547:Amantadine / Q000737:chemistry; D002151:Calorimetry; D019075:Electrophoresis, Capillary / Q000379:methods; D046209:Electrophoresis, Microchip / Q000379:methods; D005740:Gases; D007093:Imidazoles / Q000737:chemistry; D007477:Ions; D007700:Kinetics; D008024:Ligands; D013058:Mass Spectrometry; D008670:Metals / Q000737:chemistry; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation* / Q000379:methods*; D008856:Microscopy, Fluorescence; D008956:Models, Chemical; D036103:Nanotechnology; D011166:Porphyrins / Q000737:chemistry; D040081:Protein Array Analysis / Q000379:methods*; D011725:Pyridines / Q000737:chemistry; D012110:Reserpine / Q000494:pharmacology; D012984:Software; D021241:Spectrometry, Mass, Electrospray Ionization / Q000295:instrumentation* / Q000379:methods*; D013997:Time Factors; D014867:Water / Q000737:chemistry; D015032:Zinc / Q000737:chemistry; D047392:beta-Cyclodextrins / Q000737:chemistry
chemical_list: D000083:Acetanilides; D000097:Acetonitriles; D005740:Gases; D007093:Imidazoles; D007477:Ions; D008024:Ligands; D008670:Metals; D011166:Porphyrins; D011725:Pyridines; D047392:beta-Cyclodextrins; D014867:Water; C032555:1-N-butylimidazole; C051448:4-phenylpyridine; D012110:Reserpine; C019283:N-butylacetanilide; D000547:Amantadine; D015032:Zinc; C031215:betadex; C023666:pyridine; C018100:1-methylimidazole; C032159:acetonitrile