Electrospray ionization mass spectrometric detection of self-assembly of a crown ether complex directed by π-stacking interactions

Abstract

The self-assembly of ligand-metal-ligand sandwich complexes involving a novel quinoxalinecontaining crown ether, 1, was studied by electrospray ionization mass spectrometry (ESI-MS). Donor-acceptor -stacking interactions between the electron-poor quinoxaline group of 1 and electron-rich benzene groups from benzo-or dibenzo-18-crown-6 were found to significantly enhance the formation of mixed-ligand sandwich complexes with a free energy gain of up to 17 kJ/mol relative to sandwich formation involving macrocycles without such aromatic functionalities. The relative intensities of the sandwich complexes were greatest with the alkali metals Na In the present report, we present electrospray ionization mass spectrometry (ESI-MS) results on a novel crown ether which demonstrate that donor-acceptor -stacking interactions can be used to direct the self-assembly of noncovalent macrocycle-metal complexes.For probing metal complexation of macrocyclic systems, ESI-MS has proven to be an invaluable tool. Since ESI© is© capable© of© transferring© even© very© weakly© bound noncovalent complexes to the gas phase, mass spectrometry can be used to qualitatively and quantitatively evaluate the binding selectivities of the hosts or the relative binding constants of the resulting host-guest complexes© [4© -22].©Furthermore,©many©studies©have demonstrated that the results of ESI-MS analysis of these host-guest complexes correlate well with mea- Although binding of the second ligand in a ligandmetal-ligand sandwich complex in solution is typically not as strong as for the first ligand for unsubstituted crown©ethers© [27],©it©is©expected©that©the©addition©of certain functional groups on the macrocycle could enhance the formation of sandwich complexes. An analogous result has been observed for the formation of bis-crown ether-metal complexes studied by ESI-MS [13,© 23,© 28].© For© these© macrocycles,© the© preorganization offered by the covalently linked crown ethers results in very strong metal complexation in which the metal cation is simultaneously coordinated by both crown ethers.Rather than rely on covalently linked structures, such as those used in bis-crown ethers, other chemical interactions must be leveraged to create sandwich complexes which can self-assemble. -Stacking interactions, present in many biological systems and having demonstrated utility in strengthening other types of molecular interactions© [32][33][34][35],© represent© a© novel© means© of© enhanc-

ESI-MS detection of very weak π-Stacking interactions in the mixed-ligand sandwich complexes formed by substituted benzo-crown ethers and metal cations

“…The results of ESI-MS analysis of the host-guest complexes (including those involving macrocycles) correlate well with the measurements of the equilibriums in solution [7,18]. It has been clearly demonstrated by Brodbelt and coworkers that the host-guest complexes, which have similar conformations and structural features, such as a simple crown ether binding to two different alkali metal ions, have similar electrospray ionization efficiencies [19].…”

“…As clearly justified by the authors [7], the concentrations of the homo-ligand complexes ( ) can be replaced by respective peak intensities in the ESI mass spectra obtained. Further, in the same paper the Gibbs free-energy was calculated as ⌬G ϭ ϪRT lnK, and it was concluded that "large positive ⌬G values signify that the homo-ligand complexes are favored, near-zero values mean that the homo-ligand and mixed-ligand complexes are equally favored, and large negative values reflect a strong preference for formation of mixed-ligand sandwich complexes.…”

“…At this low concentration, the 2:1 complexes were characterized by low abundances in comparison to those of the 1:1 complexes; therefore the m/z range of the 2:1 complexes is magnified 10 times in Figure 1. Sherman et al [7] used a concentration of 5 ϫ 10 Ϫ5 mol/dm 3 ; however, we employed a lower concentration to minimize contamination of the instrument.…”

“…A number of sandwich type complexes have been successfully studied in detail in the gas phase [3][4][5]; some of them contained ammonium cation instead of a metal cation [6]. An interesting paper devoted to the sandwich type complexes formed by crown ethers is that published by Sherman et al [7], who demonstrated that the stability of mixed-ligand sandwich type complexes can be enhanced by -stacking interactions between two aromatic rings, one of which is enriched in electrons, while the other is poor in electrons; -stacking interactions have been also observed for some complexes of crown ethers with substituted ammonium cation [8,9]. Encouraged by this paper [7], and taking into account the importance of -stacking interactions [10 -12], we have examined whether such interactions exist in the sandwich complexes formed by amino-benzo-15-crown-5 (NH 2 B15C5) and nitro-benzo-15-crown-5 (NO 2 B15C5).…”

Anion-π interactions—interactions between benzo-crown ether metal cation complexes and counter ions

“…It has been found that cation-interactions are of crucial importance for formation of complexes between dibenzo-24-crown-8 and tetramethylammonium cation [8]. Donoracceptor -stacking interactions have been established to significantly enhance the formation of mixed-ligand sandwich complexes formed by crown ethers [9]. Crown ethers having aromatic sidearms exhibited cation-interactions between K ϩ and a benzene ring [10].…”