Noncovalent bonding

Murray, J. S., K. Paulsen, and P. Politzer. 1994. Molecular Surface Electrostatic Potentials on the Analysis of Non-Hydrogen-Bonding Noncovalent Interactions. Proc. Ind. Acad. Sci. (Chem. Sci.) 106, 267. 

J.S. Murray et al., Molecular surface electrostatic potentials in the analysis of non-hydrogen-bonding noncovalent interactions. Proc. Indian Acad. Sci. 106, 267-275 (1994)... 

Noncovalent Bonds. Noncovalent bonds are weaker than covalent bonds but arc crucial for biochemical processes such as the formation of a double helix, hour lundamental noncovalent bond types are electrostatic interactions, hydrot en bonds, van der Waals interactions, and hydrophobic inlerac-turns. T hey differ in geometry, strength, and specificity. Furthermore, these bunds are allected in vastly different ways by the presence of water. Let us consider the characteristics of each ... 

Protein tertiary (111°) structure The overall three-dimensional structure of a single polypeptide chain, including positions of disulfide bonds. Noncovalent forces such as hydrogen bonding, electrostatic forces, and hydrophobic effects are also important. 

Halogen bonding also manifests itself in the relative orientations of halogen derivatives in the crystalline state [149]. Indeed, the modes of interaction in many nonhydrogen-bonded noncovalent systems, ranging from gas phase complexes to molecular crystals, can be satisfactorily rationalized in terms of molecular surface electrostatic potentials [44,55,150]. In several instances, we have used this approach to explain anomalously high measured solid densities [151,152]. 

Both myoglobin and hemoglobin contain a prosthetic group (a nonpolypeptide part of a protein), namely heme. Prosthetic groups remain bound to the protein permanently, by covalent bonds, noncovalent bonds, or both. The protein without the prosthetic group is called an apoprotein. When an enzyme is involved, the apoprotein plus prosthetic group may be called the holoenzyme. 

An irreversible inhibitor is bound by covalent bonds. Noncovalent interactions are relatively weak and easily broken. 

Owing to a highly polarized character of hypervalent bond, noncovalent attractive interactions of a predominantly electrostatic nature are exhemely important in the stmctural chemistry of hypervalent iodine... 

Keywords Anion recognition Halogen bonding Noncovalent interactions Supramolecular chemistry... 

Fig. 5. Protein folding. The unfolded polypeptide chain coUapses and assembles to form simple stmctural motifs such as -sheets and a-hehces by nucleation-condensation mechanisms involving the formation of hydrogen bonds and van der Waal s interactions. Small proteins (eg, chymotrypsin inhibitor 2) attain their final (tertiary) stmcture in this way. Larger proteins and multiple protein assembhes aggregate by recognition and docking of multiple domains (eg, -barrels, a-helix bundles), often displaying positive cooperativity. Many noncovalent interactions, including hydrogen bonding, van der Waal s and electrostatic interactions, and the hydrophobic effect are exploited to create the final, compact protein assembly. Further stmctural...

The following sections contain a review of many of the varied synthetic systems that have been developed to date utilising noncovalent interactions to form assembhes of molecules. These sections are loosely demarcated according to the most important type of noncovalent interactions utilized in conferring supramolecular order (ie, van der Waal s interactions, electrostatic interactions, and hydrogen bonds). For extensive reviews, see References 1,2,4—6,22,46,49,110—112. Finally, the development of self-assembling, self-replicating synthetic systems is noted. 

Self-Rephca.tingSystems. Recently, molecules have been synthesized that can catalyze covalent bond-making reactions by forming a noncovalently bonded superstmcture, a maneuver that converts an intermolecular reaction into an intramolecular one. In general, in such systems, two... 

Stability of the chromophore was observed usiag uv-vis spectroscopy, the authors conclude that this sol—gel method of chromophore encapsulation does not provide any real thermal or oxidative protection in either the covalendy or noncovalently bonded state. 

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... 

This class of inhibitors usually acts irreversibly by permanently blocking the active site of an enzyme upon covalent bond formation with an amino acid residue. Very tight-binding, noncovalent inhibitors often also act in an irreversible fashion with half-Hves of the enzyme-inhibitor complex on the order of days or weeks. At these limits, distinction between covalent and noncovalent becomes functionally irrelevant. The mode of inactivation of this class of inhibitors can be divided into two phases the inhibitors first bind to the enzyme in a noncovalent fashion, and then undergo subsequent covalent bond formation. 

Two basic principles govern the arrangement of protein subunits within the shells of spherical viruses. The first is specificity subunits must recognize each other with precision to form an exact interface of noncovalent interactions because virus particles assemble spontaneously from their individual components. The second principle is genetic economy the shell is built up from many copies of a few kinds of subunits. These principles together imply symmetry specific, repeated bonding patterns of identical building blocks lead to a symmetric final structure. 

Chemistry can be divided (somewhat arbitrarily) into the study of structures, equilibria, and rates. Chemical structure is ultimately described by the methods of quantum mechanics equilibrium phenomena are studied by statistical mechanics and thermodynamics and the study of rates constitutes the subject of kinetics. Kinetics can be subdivided into physical kinetics, dealing with physical phenomena such as diffusion and viscosity, and chemical kinetics, which deals with the rates of chemical reactions (including both covalent and noncovalent bond changes). Students of thermodynamics learn that quantities such as changes in enthalpy and entropy depend only upon the initial and hnal states of a system consequently thermodynamics cannot yield any information about intervening states of the system. It is precisely these intermediate states that constitute the subject matter of chemical kinetics. A thorough study of any chemical reaction must therefore include structural, equilibrium, and kinetic investigations. 

Catalysis occurs because the catalyst in some manner increases the probability of reaction. This may result from the reactants being brought closer together [catalysis by approximation, or the propinquity effect ], or somehow assisted to achieve the necessary relative orientation for reaction. Noncovalent interactions may be responsible for the effect. Covalent bond changes may also take place in catalysis. In a formal way, the manner in which catalysis occurs can be described by schemes such as Schemes I and II. 

Chemists often call upon certain chemical types of interaction to account for solvent-solvent, solvent-solute, or solute-solute interaction behavior, and we should eon-sider how these ehemical interactions are related to the long-range noncovalent forces discussed above. The important chemical interactions are charge transfer, hydrogen bonding, and the hydrophobic interaction. 

There has been much discussion of the relative contributions of the no-bond and dative structures to the strength of the CT complex. For most CT complexes, even those exhibiting intense CT absorption bands, the dative contribution to the complex stability appears to be minor, and the interaction forces are predominantly the noncovalent ones. However, the readily observed absorption effect is an indication of the CT phenomenon. It should be noted, however, that electronic absorption shifts are possible, even likely, consequences of intermolecular interaetions of any type, and their characterization as CT bands must be based on the nature of the spectrum and the structures of the interaetants. This subject is dealt with in books on CT complexes. ... 

If the protein of interest is a heteromultimer (composed of more than one type of polypeptide chain), then the protein must be dissociated and its component polypeptide subunits must be separated from one another and sequenced individually. Subunit associations in multimeric proteins are typically maintained solely by noncovalent forces, and therefore most multimeric proteins can usually be dissociated by exposure to pEI extremes, 8 M urea, 6 M guanidinium hydrochloride, or high salt concentrations. (All of these treatments disrupt polar interactions such as hydrogen bonds both within the protein molecule and between the protein and the aqueous solvent.) Once dissociated, the individual polypeptides can be isolated from one another on the basis of differences in size and/or charge. Occasionally, heteromultimers are linked together by interchain S—S bridges. In such instances, these cross-links must be cleaved prior to dissociation and isolation of the individual chains. The methods described under step 2 are applicable for this purpose. 

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