Supramolecular chemistry goes gas phase: the mass spectrometric examination of noncovalent interactions in host–guest chemistry and molecular recognition

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␣-cyclodextrin complexes with linear ␣, -dicarboxylic acids were investigated by electrospray mass spectrometry. These hydrophobic complexes are known to have an equilibrium binding constant that increases with the diacid chain length. However, the electrospray mass spectrometry (ES-MS) spectra showed that the relative intensity of the complex did not vary significantly with chain length. This contradiction is caused by a contribution of nonspecific adducts to the signal of the complex in ES-MS. In order to estimate the contribution of nonspecific adducts to the total intensity of the complexes with ␣-cyclodextrin, the comparison was made between ␣-cyclodextrin and maltohexaose, the latter being incapable of making inclusion complexes in solution. The signal observed for complexes between diacids and maltohexaose can only result from nonspecific electrostatic aggregation, and is found to be more favorable with the shorter diacids. This is also supported by MS/MS experiments. A procedure is described which allows estimation of the contribution of the nonspecific complex in the spectra of the complexes with ␣-cyclodextrin by using the relative intensity of the complex with maltohexaose. The contribution of the specific complex to the total signal intensity is found to increase with the diacid chain length, which is in agreement with solution behavior. (J Am Soc Mass Spectrom 2002, 13, 946 -953)

mentioning

confidence: 99%

On the specificity of cyclodextrin complexes detected by electrospray mass spectrometry

Gabelica

Galić

Pauw

2002

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116

“…The permethylated derivative exhibited only a monomeric [M ϩ Na] ϩ ion at m/z 1249, and neither the dimer nor any other oligomer complex was observed. The ion at m/z 1375 is a Na ϩ adduct ion that resulted from an impurity, ␣-CD(OMe) 16 (OH) 1 (OTs) 1 . The oligomeric ions observed in 1a must be contact complexes formed by hydrogen bonding between the hydroxyl groups because no guest-substituent is present for the formation of an inclusion complex.…”

Section: Differentiation Of the Contact And The Inclusion Complexesmentioning

confidence: 99%

“…Moreover, ESI-MS can be used to study complex formation of CD with 13 different guest benzene derivatives [9] or other guest organic molecules [10], and complex formations between ␤-CD and several drugs [11][12][13][14][15] were reported. The mass spectrometric study of non-covalent interactions in host-guest chemistry and molecular recognition has been reviewed recently [16].…”

mentioning

confidence: 99%

Identification of face-to-face inclusion complex formation of cyclodextrin bearing an azobenzene group by electrospray ionization mass spectrometry

Arakawa

Yamaguchi

Takahashi

et al. 2003

The solution-based self-assembly of native and permethylated cyclodextrins (CD) bearing an azobenzene substituent has been studied by electrospray ionization mass spectrometry (ESI-MS). The results revealed that the CD molecules form either a contact or a face-to-face inclusion complex depending on the interaction of their substituents. The mass spectrometric study further demonstrated that the inclusion complex is formed through the interaction between the host CD cavity and the guest-substituent and that a contact complex is formed by hydrogen-bonding of the hydroxyl functions at the rims of the CD molecule. We also found that in order to detect the face-to-face inclusion complex by ESI-MS, the following conditions have to be met: (1) The CD moieties must be permethylated to avoid formation of the contact complex, (2) they must possess a guest-substituent of suitable length, such as an azobenzene moiety, and (3) they must possess an NH 2 or OH group at the substituent terminals for protonation and for detection as cations by ESI-MS. Formation of the inclusion complexes was further confirmed by the synthesis of a capped inclusion dimer and a capped monomer.

“…A key question revolves around the nature of the noncovalent complexes once they enter the gas phase. The specificity and the type of interactions that are retained in a solventless environment are important considerations when assessing the relevance of gas-phase results to the structures of solution-phase complexes [1][2][3][4][5]. Information on the relative stabilities of noncovalent complexes is often obtained from their gas-phase dissociation behavior [6], and many recent examples of biologically interesting macromolecular complexes demonstrate the importance of electrostatic interactions and hydrogen bonds in maintaining these noncovalent associations in the gas phase [7][8][9][10][11][12][13][14].…”

mentioning

confidence: 99%

“…Hydrogen bonds also span a range of bond distances and angles, with near-linear bonds generally being the strongest. Assessing the strength of hydrogen bonding interactions and correlating the interactions with structural factors should lead to a better understanding of the stabilities of noncovalent complexes in the gas phase [1][2][3][4][5]. Is the magnitude of the electrostatic interactions in a particular noncovalent complex the only determinant of gas-phase stability?…”

mentioning

confidence: 99%

Threshold dissociation energies of protonated amine/polyether complexes in a quadrupole ion trap

David

Brodbelt

2003

Electrospray ionization mass spectrometry (ESI-MS) is increasingly used to probe the nature of noncovalent complexes; however, assessing the relevance of gas-phase results to structures of complexes in solution requires knowledge of the types of interactions that are maintained in a solventless environment and how these might compare to key interactions in solution. This study addresses the factors impacting the strength of hydrogen bonding noncovalent interactions in the gas phase. Hydrogen bonded complexes consisting of ammonium ions bound to polydentate ethers are transported to the gas phase with ESI, and energy-variable collisional activated dissociation (CAD) is used to map the relative dissociation energies. The measured relative dissociation energies are correlated with the gas-phase basicities and steric factors of the amine and polyether constituents. To develop correlations between hydrogen bonding strength and structural features of the donor and acceptor molecules, a variety of amines with different gas-phase basicities and structures were selected, including primary, secondary, and tertiary amines, as well as those that are bidentate to promote intramolecular hydrogen bonding. The acceptor molecules are polydentate ethers, such as 18-crown-6. Four primary factors influence the observed dissociation energies of the polyether/ammonium ion complexes: the gas-phase basicities of the polyether and amine, steric effects of the amines, conformational flexibility of the polyethers, and the inhibition of intramolecular hydrogen bonds of the guest ammonium ions in the resulting ammonium/polyether noncovalent complexes. E lectrospray ionization mass spectrometry (ESI-MS) is being increasingly used for the analysis of noncovalent complexes, especially those involving biomolecules, because it is a "soft" method for the transfer of solution species into the gas phase [1][2][3][4][5]. A key question revolves around the nature of the noncovalent complexes once they enter the gas phase. The specificity and the type of interactions that are retained in a solventless environment are important considerations when assessing the relevance of gas-phase results to the structures of solution-phase complexes [1][2][3][4][5]. Information on the relative stabilities of noncovalent complexes is often obtained from their gas-phase dissociation behavior [6], and many recent examples of biologically interesting macromolecular complexes demonstrate the importance of electrostatic interactions and hydrogen bonds in maintaining these noncovalent associations in the gas phase [7][8][9][10][11][12][13][14]. In some cases, the stabilities of complexes obtained based on gas-phase measurements do not correlate well with those obtained in solution [14], whereas other reports have shown remarkable agreement between gas-phase and solution results [13].Hydrogen bonds are one of the most important types of noncovalent interactions in the gas phase, both in simple protonated molecules, such as peptides and proteins, and in large biological com...