Molecular recognition by mass spectrometry SUPRAMOLECULAR CHEMISTRY AND MASS SPECTROMETRY

Abstract

A recent major advance in the field of mass spectrometry in the biomolecular sciences is represented by the study of the supramolecular interactions among two or more partners in the gas phase. A great deal of chemistry and most of biochemistry concerns molecular interactions taking place in solution. The electrospray technique, which allows direct sampling from solution, and soft ionization of the solute without deposition into the analyte of large amounts of energy, guarantees in many cases the survival of noncovalent bondings and, hence, the direct analysis of the supramolecular complexes present in the condensed phase. The proper preparation of the solution to be studied and also the expert and accurate setting and use of the instrumental parameters are the prerequisites for gaining results as to the specific interactions between, for instance, a protein conformationally modified by its specific metal ion, eventually, and a ligand molecule. The analysis of the charge state of the protein itself and of the modifications of the complex integrity by activating collisions are also methods for studying the biomolecule–molecule interactions. Accordingly, this new mass spectrometric approach to the supramolecular chemistry, which could be also defined as 'supramolecular mass spectrometry', allows the study of ion–protein, protein–protein, protein–ligand and DNA–drug interactions. Chiral recognition can also be performed in the gas phase, studying by electrospray mass spectrometry the fragmentation of diastereomeric complex ions. Not the least, a deep insight can also be obtained into the formation and nature of inclusion complexes like those formed with crown ethers, cyclodextrins and calixarenes as host molecules. All these topics are treated to a certain extent in this special feature article. Most biochemical functions involve, at the molecular level, noncovalent bonding. It is well known that storage and replication of genetic information and base stacking in the DNA double helix depend on hydrogen bonding. Practically all the reactions in the cell are catalyzed by enzymes, often requiring the reversible binding of the substrate to the enzyme; also the inhibition mechanism may work through noncovalent binding. Covalent catalysis and inhibition are also conceivable mechanisms, but always the reaction path encompasses a molecular recognition step. It has been observed, also, that for the efficient transport of the oxygen molecule through the blood stream, ˛ 2 -tetramers of the Ł Correspondence to: