Noncovalent molecular complex

As a final example we consider noncovalent molecular complex formation with the macrocyclic ligand a-cyclodextrin, a natural product consisting of six a-D-glucose units linked 1-4 to form a torus whose cavity is capable of including molecules the size of an aromatic ring. Table 4-3 gives some rate constants for this reaction, where L represents the cyclodextrin and S is the substrate ... 

We now inquire into the nature of solvent effects on chemical equilibria, taking noncovalent molecular complex formation as an example. Suppose species S (substrate) and L (ligand) interact in solution to form complex C, K, being the complex binding constant. 

So far, the studies of cucurbituril described have been thermodynamic investigations, in which factors contributing to the overall stability of molecular complexes have been explored. While bounteous, these only partly address the question of receptor specificity. For example, in biological systems the kinetics of noncovalent interactions, such as between enzymes and substrates, may be of greater consequence. Clearly, the dynamics of molecular recognition deserve additional attention. Cucurbituril provides diverse opportunities in this area [11]. 

Molecular Complexes. These species are formed by noncovalent interactions between the substrate and ligand. Among the kinds of complexspecies included in this class are small molecule-small molecule complexes, small molecule-macromolecule species, ion-pairs, dimers and other self-associated species, and inclusion complexes in which one ofthe molecules, the host, forms or possesses a cavity into which it can admit a guest molecule. 

Lipids, by virtue of their immiscibility with aqueous solutions, depend on protein carriers for transport in the bloodstream and extracellular fluids. Fat-soluble vitamins and free fatty acids are transported as noncovalent complexes. Vitamin A is carried by retinol-binding protein and free fatty acids on plasma albumin. However, the bulk of the body s lipid transport occurs in elaborate molecular complexes called lipoproteins. 

Therefore, Sustmann felt that it would be desirable to devise a more comprehensive explanation of the regioselectivity in the cycloaddition of diazomethane. Sustmann and Sicking (1987 a) developed a program, called PERVAL (/ enurbation + eva/ua-tion) that makes use of graphical evaluations of the numerical results. Its fundamental perturbation theory is based on the MINDO/3 approximation. The program allows differentiation between covalent and noncovalent interactions in a molecular complex (see, for its first application for cycloadditions of formonitrile oxide, Sustmann and Sicking, 1987 b). 

Van der Waals interactions, or noncovalent-bonded interactions, play an essential role of intermolecular interaction potentials in condensed matter physics, materials chemistry, and structural biology. These interactions are crucial for understanding and predicting the thermodynamic properties of liquids and solids [1], the energy transfers among molecular complexes [2], and the conformational tertiary structures of nanostructures. Intermolecular bonds do not originate from sharing of electrons... 

Analogs of biomolecules carrying an attached second component have sometimes been referred to as bioconjugates as well. Furthermore, the term bioconjugation has been used in numerous cases when noncovalent molecular interactions were considered, for example, in the complexation of glycosami-noglycans and proteins such as heparin sulfate and growth factors. 

The kinds of noncovalent interactions that give rise to van der Waals forces are particularly important in determining the structures and properties of molecular complexes. Hobza, P. Zahradnik, R. Miiller-Dethlefs, K. Collect. Czech. Chem. Commun. 2006, 71, 443. 

The formation of solvent—analyte noncovalently bound complexes (e.g., [M -F H + ACN], [M -F H -F MeOH]", etc.) complicates molecular ion determination in ESI—APCI MS (Table 10.1). The relative abundances of these solvent cluster ions depend on the components in the solution phase, ionization mode, spray voltage, capillary temperature, sheath gas pressure, as well as auxiliary gas flow. Zhao et al. (2004) recently reported that acetonitrile could be reduced to ethyl amine under ESI conditions (Scheme 1). They demonstrated that the M -F 46 ion in the mass spectrum represented the ethyl amine adduction ([M -F H -F CH3CH2NH2] ) when the ESI—MS was performed by infusion of the compound in acetonitrile and water (1% HCOOH -F 1% NH4OH) (1 1 V v). Moreover, they showed the same analyte produced a moderate [M + H + CD3CH2NH2] (M -F 49) signal when acetonitrile-ds was used as the organic solvent (Scheme 1). 

Molecular recognition and noncovalent complexes are at the core of reaction networks in biology. Molecular complexes are often associated with the proliferation of disease (see, for example, the Tax-associated complexes in human T-cell leukemia type 1, HTLV-1 [33]). Along with other competing techniques (e.g., surface plasmon resonance), mass spectrometry can be successfully used to detect noncovalent complex formation. The corresponding ions can be present in both MALDl [34] and ESI [35] spectra, although the latter is used more often. A wide variety of protein-protein interactions as well as protein interactions with other species (nucleotides, carbohydrates, etc.) have been studied. The spectra can reveal the components of the complex and in some cases the association constant. 

Initially, most or even all known MALDI matrices were acidic compounds, such as benzoic and cinnamic acid derivatives. However, the acidic medium is not well-suited to keeping noncovalently bound complexes intact. In the 1990s, a couple of groups therefore introduced a number of nonacidic MALDI matrices such as 2-amino-4-methyl-5-nitropyridine, />ara-nitroaniline, or 6-aza-2-thio-thymine. These were shown to be beneficial for MALDI MS of noncovalent complexes—for example, to keep peptide-oligonucleotide complexes or DNA duplexes intact.However, their performance at high molecular... 

Size Isomers. In solution, hGH is a mixture of monomer, dimer, and higher molecular weight oligomers. Furthermore, there are aggregated forms of hGH found in both the pituitary and in the circulation (16,17). The dimeric forms of hGH have been the most carefully studied and there appear to be at least three distinct types of dimer a disulfide dimer connected through interchain disulfide bonds (8) a covalent or irreversible dimer that is detected on sodium dodecylsulfate- (SDS-)polyacrylamide gels (see Electroseparations, Electrophoresis) and is not a disulfide dimer (19,20) and a noncovalent dimer which is easily dissociated into monomeric hGH by treatment with agents that dismpt hydrophobic interactions in proteins (21). In addition, hGH forms a dimeric complex with ( 2). Scatchard analysis has revealed that two ions associate per hGH dimer in a cooperative... 

Up to this point, we have emphasized the stereochemical properties of molecules as objects, without concern for processes which affect the molecular shape. The term dynamic stereochemistry applies to die topology of processes which effect a structural change. The cases that are most important in organic chemistry are chemical reactions, conformational changes, and noncovalent complex formation. In order to understand the stereochemical aspects of a dynamic process, it is essential not only that the stereochemical relationship between starting and product states be established, but also that the spatial features of proposed intermediates and transition states must account for the observed stereochemical transformations. 

---