Directional covalency

Unlike the forces between ions which are electrostatic and without direction, covalent bonds are directed in space. For a simple molecule or covalently bonded ion made up of typical elements the shape is nearly always decided by the number of bonding electron pairs and the number of lone pairs (pairs of electrons not involved in bonding) around the central metal atom, which arrange themselves so as to be as far apart as possible because of electrostatic repulsion between the electron pairs. Table 2.8 shows the essential shape assumed by simple molecules or ions with one central atom X. Carbon is able to form a great many covalently bonded compounds in which there are chains of carbon atoms linked by single covalent bonds. In each case where the carbon atoms are joined to four other atoms the essential orientation around each carbon atom is tetrahedral. 

The compounds of carbon and silicon with hydrogen would be expected to be completely covalent according to these models, but the dhectionality of the bonds, which is towards the apices of a regular tetrahedron, is not explained by these considerations. Another of Pauling s suggestions which accounts for this type of directed covalent bonding involves so-called hybrid bonds. 

Interatomic potentials began with empirical formulations (empirical in the sense that analytical calculations based on them... no computers were being used yet... gave reasonable agreement with experiments). The most famous of these was the Lennard-Jones (1924) potential for noble gas atoms these were essentially van der Waals interactions. Another is the Weber potential for covalent interactions between silicon atoms (Stillinger and Weber 1985) to take into account the directed covalent bonds, interactions between three atoms have to be considered. This potential is well-tested and provides a good description of both the crystalline and... 

Mercury has a characteristic ability to form not only conventional ammine and amine complexes but also, by the displacement of hydrogen, direct covalent bonds to nitrogen, e.g. ... 

Huggins (1922) was the first investigator to assign structures to sphalerite, wurtzite, chalcopyrite, pyrite, marcasite, arsenopyrite, and other sulfide minerals in which each sulfur atom forms four tetrahedrally directed covalent bonds with surrounding atoms. These structures would be described as involving quadricovalent argononic S2+. 

The partitioning of the activated inhibitor between direct covalent inactivation of the enzyme and release into solution is an important issue for mechanism-based inactivators. The partition ratio is of value as a quantitative measure of inactivation efficiency, as described above. This value is also important in assessing the suitability of a compound as a drug for clinical use. If the partition ratio is high, this means that a significant proportion of the activated inhibitor molecules is not sequestered as a covalent adduct with the target enzyme but instead is released into solution. Once released, the compound can diffuse away to covalently modify other proteins within the cell, tissue, or systemic circulation. This could then lead to the same types of potential clinical liabilities that were discussed earlier in this chapter in the context of affinity labels, and would therefore erode the potential therapeutic index for such a compound. 

Activity-based protein profiling (ABPP) is a chemical proteomic strategy in which active-site-directed covalent probes are used to profile the functional states of enzymes in complex proteomes. Activity-based probes (ABPs) can distinguish active enzymes from their inactive zymogens or inhibitor-bound forms. They contain a reactive group intended to modify enzyme active sites covalently and a reporter group (typically rhodamine or biotin) that assists in detection and identification of protein targets. 

N-AryInitrones (XIII) formed by oxidation of N-hydroxy-N-methyl arylamines, show high reactivity toward carbon-carbon and carbon-nitrogen double bonds in non-aqueous media (21,203) (Figure 10). Under physiological conditions, however, it appears that N-arylnitrones exist as protonated salts that readily hydrolyze to formaldehyde and a primary N-hydroxy arylamine and efforts to detect N-arylnitrone addition products in cellular lipid, protein or nucleic acids have not been successful (204). Nitroxide radicals derived from N-hydroxy-MAB have also been suggested as reactive intermediates (150), but their direct covalent reaction with nucleic acids has been excluded (21). 

Rideout, D., Calogeropoulou, T., Jaworski, J., and McCarthy, M. (1990) Synergism through direct covalent bonding between agents A strategy for rational design of chemotherapeutic combinations. Biopolymers 29, 247-262. 

Another alternative is for the enzyme to actually form a covalent bond between the enzyme and the substrate. This direct, covalent participation of the enzyme in the chemical reaction is termed covalent catalysis. The enzyme uses one of its functional groups to react with the substrate. This enzyme-substrate bond must form fast, and the intermediates must be reasonably reactive if this kind of catalysis is going to give a rate acceleration. 

Soon after the quantum revolution of the mid 1920s, Linus Pauling and John C. Slater expanded Lewis s localized electronic-structural concepts with the introduction of directed covalency in which bond directionality was achieved by the hybridization of atomic orbitals.1 For normal and hypovalent molecules, Pauling and Slater proposed that sp" hybrid orbitals are involved in forming shared-electron-pair bonds. Time has proven this proposal to be remarkably robust, as has been demonstrated by many examples in Chapter 3. 

Pauling s landmark 1931 paper9 established the fundamental principles of the directed covalent bond ... 

The most critical aspect of atomistic simulations is thus the representation of the interactions between atoms by an algebraic function. If covalency is important, a part of the expression should contain details of how the interaction changes with angle, to mimic directional covalent bonds. In cases where a simulation is used to predict the location of a cluster of atoms within or at the surface of a solid, interactions between the atoms in the cluster, interactions between the atoms in the solid, and interactions between the atoms in the cluster and those in the solid must all be included. 

Finally - and perhaps most importantly - the fluorous tagging of the catalyst that introduces affinity for the fluorous phase can be a very mild immobilization technique, as there is no direct covalent link with a support and the sepa-... 

Direct consumption sugar, 23 450-451 Direct contact heat exchangers, 13 268 Direct cooler evaporators, 21 537 Direct-coupled plasma (DCF), 25 370 Direct covalent carbon nanotube functionalization, 17 54-55 Direct current (dc) diode sputtering, 24 730-731. See also dc sensing current... 

Laboratory procedures are presented for two divergent approaches to covalent structure controlled dendrimer clusters or more specifically - core-shell tecto(dendrimers). The first method, namely (1) the self assembly/covalent bond formation method produces structure controlled saturated shell products (see Scheme 1). The second route, referred to as (2) direct covalent bond formation method , yields partial filled shell structures, as illustrated in Scheme 2. In each case, relatively monodispersed products are obtained. The first method yields precise shell saturated structures [31, 32] whereas the second method gives semi-controlled partially shell filled products [30, 33],... 

The second method referred to as the direct covalent bond formation method , produces semi-controlled, partial shell filled structures. It involves the reaction of a limited amount of nucleophilic dendrimer core reagent with an excess of... 

The design of our conformationally constrained aminoglycosides is based on the structural information available for the RNA-paromomycin complex [21-26]. It is known that positions 05m and N2i are hydrogen bonded within the ribosome bound state. Thus, in our analogs, this interaction has been replaced by either a direct covalent bond, as in 2, a two-methylene bridge, as in 3, or by a salt bridge, as in 4 (see Fig. 9). 

Accordingly, many reactions can be performed on the sidewalls of the CNTs, such as halogenation, hydrogenation, radical, electrophilic and nucleophilic additions, and so on [25, 37, 39, 42-44]. Exhaustively explored examples are the nitrene cycloaddition, the 1,3-dipolar cycloaddition reaction (with azomethinylides), radical additions using diazonium salts or radical addition of aromatic/phenyl primary amines. The aryl diazonium reduction can be performed by electrochemical means by forming a phenyl radical (by the extrusion of N2) that couples to a double bond [44]. Similarly, electrochemical oxidation of aromatic or aliphatic primary amines yields an amine radical that can be added to the double bond on the carbon surface. The direct covalent attachment of functional moieties to the sidewalls strongly enhances the solubility of the nanotubes in solvents and can also be tailored for different... 

In contrast to the use of self-assembly reactions and metal ion coordination preferences to direct the construction of mixed cofactor systems, the use of SPPS or selective chemical ligation allows for the direct covalent attachment of cofactors for the construction of mixed cofactor systems within de novo design. Figure 11 shows the flavocy-tochrome maquette constructed by Dutton and co-workers (149) using a flavin moiety covalently attached to a unique cysteine residue inside a four helix bundle with bis-histidine binding sites for heme... 

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