Molecular macrocyclic chemistry

Historically, the concept of coordination chemistry was associated with complexation of a metal cation (Lewis acid) by a ligand behaving as a Lewis base. Such was traditionally the case for macrocyclic molecules as ligands. In the early 1970s, however, the concept of coordination chemistry was extended in the area of macrocyclic chemistry to include molecular cations, neutral molecules and anions as substrates. Complexes of all of these species are to be included in the scope of this chapter section. Examples of the types of substrates are discussed below. 

We shall now discuss several recognition processes and describe the main properties of the corresponding molecular receptors. Insofar as receptor molecules have cyclic geometries and contain cavities into which the substrate(s) may bind, the chemistry of molecular recognition also covers macrocyclic chemistry and inclusion chemistry. In view of the extensive literature concerning these domains, the reader is referred to specific monographs, reviews or original papers for more information (see Appendix). 

Macrocyclic chemistry spans the whole range from molecular recognition to template effects to STM experiments. The fundamentals for the development of macrocyclic molecules with more complex functions are laid. This basic knowledge that has been compiled over years, allows us now to more elaborate systems with diversity of functionalities. We discussed two of the many methods used in this respect, template and self-assembly strategies, and their combination. Current research in this area includes construction of systems bearing functions that allow incorporation into high-order architectures. 

AnaLig sorbents, with predetermined molecular recognition chemistry for specific ions, using immobilized macrocycles Pb from fresh and seawater, Cu, Ni from drug extract, Fe, NI from petroleum, Hg from water 111... 

As macrocyclic chemistry has developed, the variety and scope of the applications of these molecules have continued to multiply. This concluding section is an attempt to provide an overview of only three of the applications of synthetic macrocycles. A particularly insightful treatment can be found in the Nobel Lecture of Jean-Marie Lehn, which describes the concept of supramolecular chemistry from simple recognition, to cation and anion receptors, multiple recognition, catalysis, transport, and molecular devices. 

The preceding molecular baskets belong broadly to two classic classes of macrocycles namely the calixarenes and cycloveratrylenes. There are several other macrocycles with the potential to bind guests in an aromatic-rich cavity that are worthy of discussion. Of the vast amount of work that emanated from the Cram group, the rigid spherands and carcerands stand out. In addition there are the cyclophanes and Baeyer s early contribution to macrocyclic chemistry, resorcinar-enes and calixpyrroles. 

The first macrocyclic steroid derivative intended for use in molecular recognition chemistry has been synthesized by direct cyclodimerization of amide 99, which in turn was prepared from acid 97 and amine 98 using DEPC.38... 

R208 A. Moreira da SUva, Food Antioxidants Cyclodextrin Inclusion Compounds Molecular Spectroscopic Studies and Molecular ModeUing , in Macrocyclic Chemistry, eds. D. W. Fitzpatrich and H. J. Ulrich, Nova Science Pubhshers, Inc. Hauppauge, N. Y., 2010, p. 447. 

Since the seminal works on macrocyclic ligands by Pedersen [1,2], Lehn [3,4], and Cram [5, 6] macrocyclic chemistry has prospered over the past four decades to become one of the most dynamic and promising frontiers of chemical research, offering specific and selective molecular recognition, self-organization, and specific... 

Since the pioneering work of Charles J. Pedersen, Donald J. Cram and Jean-Marie Lehn, macrocyclic chemistry attracted a considerable attention from chemists all over the world [1-4]. An ability of macrocycles to be highly selective receptors (host molecules) for a number of metal and organic cations or anions, as well as for the small or even huge (e.g. fiillerenes) neutral organic substances is the reason of that interest [5-8]. The design of molecular devices such as molecular containers and reactors on one hand, and molecular switches (based on catenanes and molecular knots) on the other hand is another area of the macrocyclic chemistry application. So, the macrocyclic chemistry plays an important role in the material science, especially in the constmction of nano-sized materials on the bottom-up principles [5, 6, 9-11]. 

Calixarenes, which are macrocyclic compounds, are one of the best building blocks to design molecular hosts in supramolecular chemistry [158]. Synthesis of calix[4]arenes, which have been adamantylated, has been reported [105, 109]. In calix[4]arenes, adamantane or its ester/carboxylic acid derivatives were introduced as substituents (Fig. 29). The purpose of this synthesis was to learn how to employ the flexible chemistry of adamantane in order to construct different kinds of molecular hosts. The X-ray structure analysis of p-(l-adamantyl)thiacalix[4]arene [109] demonstrated that it contained four CHCI3 molecules, one of which was located inside the host molecule cavity, and the host molecule assumed the cone-like conformational shape (Fig. 30). 

Adamantane can be used to construct peptidic scaffolding and synthesis of artificial proteins. It has been introduced into different types of synthetic peptidic macrocycles, which are useful tools in peptide chemistry and stereochemistry studies and have many other applications as well. Introduction of amino acid-functionalized adamantane to the DNA nanostmctures might lead to construction of DNA-adamantane-amino acid nanostmctures with desirable stiffness and integrity. Diamondoids can be employed to constmct molecular rods, cages, and containers and also for utilization in different methods of self-assembly. In fact, through the development of self-assembly approaches and utilization of diamondoids in these processes, it would be possible to design and constmct novel nanostmctures for effective and specific carriers for each dmg. 

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