Chemistry-based approaches

Chemistry-based approaches start by postulating a structure that satisfies the rules of chemistry and then look for ways in which this structure can be mapped into three-dimensional space. The chemical constraints are the ones that 

Central to the chemistry-based approaches is the Hierarchical principle (Hawthorne 1985) which states  

Rule 11.5 (Hierarchical principle). When generating a chemical structure, the strongest bonds are formedfirst, followed by the others in decreasing order of their valence. 

The three stages of bond formation are not present in all compounds. Binary compounds like NaCl (18189) only show the second stage, the stage which all materials must undergo when they solidify. Since inorganic compounds can only be characterized by the structures of their crystalline solids, the second stage determines which compounds can exist. 

The first step in any chemical approach to crystalline structure is to determine the short-range order, i.e. which atoms are bonded. The most convenient way of doing this is by means of the bond graph described in Section 2.5. In many cases all or most of the bond graph can be determined from first principles, since, except for the weakest bonds created in the post-crystallization stage, the bond graph is determined by the rules of chemistry, particularly the hierarchical principle (Rule 11.5), the valence matching principle (Rule 4.2), and the principle of maximum symmetry (Rule 3.1). 

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N. C. Gianneschi, M. S. Masar, and C. A. Mirkin, Development of a coordination chemistry-based approach for functional supramolecular structures, Acc. Chem. Res., 38 (2005) 825-837. 

A series of symmetric multinuclear complexes (67-69,127-129) were reported since 1986, illustrating the coordination chemistry-based approach for the design of supramolecular materials. They were generated by attaching six [Fe(CN)5] , [Ru(NH3)5] +, or [Ru(edta)] groups to the peripheral N-atoms of the multibridging tris-bipyrazineruthenium(II), [Ru(bpz)3], complex (Fig. 8). The... 

Some recent developments concerning macromolecular quantum chemistry, especially the first linear-scaling method applied successfully for the ab initio quality quantum-chemistry computation of the electron density of proteins, have underlined the importance and the applicability of quantum chemistry-based approaches to molecular similarity. These methods, the linear-scaling numerical Molecular Electron Density Lego Approach (MEDLA) method [6 9] and the more advanced and more generally applicable linear-scaling macromolecular density matrix method called Adjustable Density Matrix Assembler or ADMA method [10,11], have been employed for the calculation of ab initio quality protein electron densities and other... 

This chck chemistry-based approach to ABPP even works in live animals to determine specific protein expression levels. As an example, PS-N3 (366) was injected into living mice to investigate ECH-1 expression in the heart tissue. One hour after injection, the mice were sacrificed, and ECH-1 was successfully detected by staining the crude heart-homogenate via Cu(l)-catalyzed bioconjugation using a Rh-alkyne tag 367 (Scheme 74B) [233]. 

In the first part of this review article, we have surveyed the click chemistry-based approaches to purely organic rotaxanes and discussed a few particularly efficient syntheses. Not too surprisingly, the copper(I)-catalyzed click reaction does not seem to be affected by the threaded nature of the precursors. In fact, since there is no interference between copper(I) and the functional groups borne by the organic fragments of the rotaxane precursor, rotaxane synthesis works as efficiently as classical click reactions with non-threaded precursors. 

Toma HE, Araki K (2009) Exploring the supramolecular coordination chemistry-based approach for nanotechnology. In Karlin KD (ed) Progress in inorganic chemistry, vol 56. Wiley, Hoboken, pp 379 85... 

Today, CuAAC and copper-free click chemistry are serving as complementary approaches to modify biomolecules for both in vitro and in vivo applications. In this chapter, we will highlight the recent applications of these triazole-forming reactions to the imaging and profiling of biomolecules. Comprehensive reviews of click chemistry-based approaches for bioconjugation have been published recently [12, 29]. 

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