9.12. Mass Spectrometric Studies of Host–Guest Complexes of Glucosylcalixarenes

Public examination of a doctoral dissertation in the field of chemistry

Doctoral candidate: Licentiate in Philosophy Mika Torvinen 

Date and venue: 9.12.2011, at 12 noon, F100, Futura, Joensuu campus

ABSTRACT 

The binding, transport and release of biologically important compounds by synthetic receptors are topics of great interest in supramolecular and bioorganic chemistry. Over the past years, a variety of hosts have been synthesized for molecular recognition of different compounds, such as amino acids and peptides. Macrocyclic calixarenes, for example, contain intramolecular cavities, which are optimal for the binding of various molecules and ions. Calixarenes are also relatively easy to synthesize and their reactive rims can be functionalized to enhance the ability for specific molecular recognition. Glycosylcalixarenes, for example, are particularly attractive host molecules, since carbohydrates have major roles in many important biological processes, such as tumor metastasis, intercellular communication and targeting of antibodies. Amino, amide, urea, thiourea and guanidium substituents have commonly been used as ligating units, but only a few studies have been concerned with the molecular recognition of natural compounds by carbohydrate containing receptors. Even fewer studies have been performed in the gas phase, although such studies could provide useful information for the design of new efficient and selective receptors. 

In this study, noncovalent complexation between different glucosylcalixarenes and a variety of guests, including amino acids, carboxylic acids, monoamine transmitters and bisphophonates, was studied with electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI-FTICR MS) and ab initio calculations. Solution competition experiments, collision induced dissociation (CID) experiments and gas-phase ion/molecule reactions were used. 

The main interests of this study were to find affinity trends towards certain structural features of the guests, to study binding models and conformations of the glucosylcalixarenes and to see how the structural features of the glucosylcalixarenes affect both the complex formation and the stabilities of the complexes. Considerable attention was also paid to the isomeric and enantiomeric selectivity of the glucosylcalixarenes towards the guest compounds. 

It was observed that the glucosylcalixarenes form complexes with a variety of guest compounds with the binding being clearly dependant on the specific structural features of the guest. The complexes were mainly stabilized by hydrogen bonds, but the π-electron nature of the guest also had effect on the complexation. There was also indicative evidence that the characteristics of the glucosylcalixarenes depend on the number of glucosyl units at the upper rim and the length of the alkyl chains at the lower rim of the calixarene skeleton. The increased number of glucose units, for example, enabled the glucosylcalixarenes to gain higher charge states, as well as to adopt multiple gas-phase conformations. Competition experiments carried out with d- and l-forms of some amino acids showed enantiomeric selectivities ranging from 0.61 to 2.58. Also, a clear isomeric selectivity for some dicarboxylic acid anions was observed, which seems to originate from the intramolecular hydrogen bonding of the guest anions. Most interestingly, certain metal ions were efficiently used to trigger the release of the bisphosphonate drugs from the glucosylcalixarene complexes. 

The doctoral dissertation of Licentiate in Philosophy Mika Torvinen entitled “Mass Spectrometric Studies of Host-Guest Complexes of Glucosylcalixarenes” will be examined at the Faculty of Science and Forestry.The opponent in the public examination is Professor Maija Nissinen from the University of Jyväskylä and the custos is Professor Janne Jänis of the University of Eastern Finland.

Photo available for download at http://www.uef.fi/vaitoskuvat

Contact: Mika Torvinen, tel. +358 50 410 5877, mika.torvinen@uef.fi

Publishing year: 2011

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