Nitrate Hybrid Molecules

The chemical properties of nitric acid require us to consider the structure first. The vapour of pure nitric acid (i.e. anhydrous) is probably composed of molecules of hydrogen nitrate , which structurally is a resonance hybrid of such forms as ... 

Valence bond theory (Chapter 7) explains the fact that the three N—O bonds are identical by invoking the idea of resonance, with three contributing structures. MO theory, on the other hand, considers that the skeleton of the nitrate ion is established by the three sigma bonds while the electron pair in the pi orbital is delocalized, shared by all of the atoms in the molecule. According to MO theory, a similar interpretation applies with all of the resonance hybrids described in Chapter 7, including SO S03, and C032-. 

Because all three bonds are identical, a better model of the nitrate ion is a blend of all three Lewis structures with each bond intermediate in properties between a single and a double bond. This blending of structures, which is called resonance, is depicted in (9) by double-headed arrows. The blended structure is a resonance hybrid of the contributing Lewis structures. A molecule does not flicker between different structures a resonance hybrid is a blend of structures, just as a mule is a blend of a horse and a donkey, not a creature that flickers between the two. 

When two or more different primary plosophores are present in a single molecule, the compd is called hybrid (eg nitrate aliphatic nitro, nitrate aromatic nitro, nitramine aromatic nitro). It was established that hybrids are as powerful (or more) as pure types, although they tend to exhibit somewhat greater variability. This property of hybrids is of importance, because it extends enormously the synthetic possibilities for expls... 

Resonance is by no means restricted to organic molecules. The following sets of valence-bond structures represent the hybrid structures of nitrate ion, NO30, carbonate ion, CO320, and nitrous oxide, NaO. These are only representative examples. We suggest that you check these structures carefully to verify that each member of a set conforms to the general rules for resonance summarized above. 

The two calix[4]arenes, 24 and 26, are examples of useful derivatives the former binds lanthanides to form luminescent complexes, the latter, prepared from compound 25, is water soluble and crystallizes in a variety of forms, from laminates to nanospheres. Other derivatives are to be found in the literature. Simple derivatives, such as the O-alkyl compounds, are used as a basis for upper rim functionalization treatment of these compounds with nitric acid replaces the upper f-butyl groups with nitrates. Nitrocalixarenes can be reduced to the corresponding amines to generate a platform for further extension of the cavity and have been used to bind metals or small molecules. Oxa- and azacalix[3]arenes represent crown ether-calixarene hybrids and have binding modes reminiscent of both classes of molecules. Many alternative upper rim substituents can be introduced and, in the case of the azacalixarenes, the /V-substituent can easily be varied. 

The anionic interchange method involves the dispersion of LDH materials into a monomer solution, most often in aqueous mediiun (path 1 in Fig. 6) [52-54]. The dispersion is then stirred for several horns with mild heating. To be able to replace the interlayer anion, the monomer molecules should have such functionality as can stabilize the layered structure by neutralizing the excess charge on the hydroxide sheets of LDH. For example, acrylate anions are intercalated into Mg - Al LDH through ion exchange with Cl" or NO3" present in LDH. Lee and Chen reported intercalation of acrylate and 2-acryloamido-2-methyl propane sulfonate into hydrotalcite [51]. These intercalated hybrids are then dispersed in an alkah-neutralized solution of the monomer and the polymerization is carried out in the presence of an initiator. Leroux and coworkers prepared vinylbenzene sulfonate monomer intercalated Zn-Al LDH [52] and aminobenzene sulfonate monomer intercalated Cu-Cr LDH [53]. Further, Tanaka et al. reported acrylate ion intercalation within LDH by replacing the nitrate anion from Mg-Al LDH [54]. 

Fig. 20.2 Six representative hybrid NORMs eontaining furoxan, nitrate, and NONOate warheads. Eaeh molecule incorporates at least two eomponent parts a bioactive carrier and a warhead. All examples shown have labile linkers that are bioactivated to release bioaetive molecules ineluding the warhead. In most eases the warhead requires further bioactivation to release NO bioaetivity. The figure illustrates the uniform dependence on reactions with biological thiols and products that will contribute to varied levels of cellular oxidative stress...

The NO-ASA family of NO-NSAIDs, notably NCX 4016 [Fig. 20.2(a)] and NCX 4040 [Fig. 20.2(b)], has been extensively researched. These two isomeric hybrid NORMS differ only in the snbstitution of the linker group. Hulsman et al. was the first to comment that in NCX-4040 the presnmed invisible linker is in fact solely responsible for the anti-tumor effect of the molecule and that both the NO-release warhead and the ASA are passive bystanders (Hulsman, Medema et al. 2007). The Unker warhead moiety is efficiently bioactivated to a quinone methide thiophiUc electrophile, in simile with much earUer literature reports (Myers and Widlanski 1993). Molecules in which the nitrate group of NO-ASA was replaced by a comparably good leaving group (termed X-ASA Fig. 20.12) showed very similar properties in vitro with respect to activity (1) cytotoxic/genotoxic (2) antiproliferative (3) chemopreventive (ARE activation - phase 11 enzyme induction) and (4) the anti-inflammatory (Dunlap et al. 2(X)7, 2008). 

PRACTICE EXAMPLE A Draw Lewis structures to represent the resonance hybrid for the SO2 molecule. PRACTICE EXAMPLE B Draw Lewis structures to represent the resonance hybrid for the nitrate ion. 

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