Conformational structure inherently chirality

An alternative statement of this rule is that a molecule cannot be optically active if it is in equilibrium with a structure (or a conformation) that is achiral. Inherently chiral compounds have NO achievable achiral conformations. Because conformers differ only by rotations about single bonds, they are generally in equilibrium at room temperature. We can consider cyclohexane rings as though they were flat (the most symmetric conformation), and we should consider straight-chain compounds in their most symmetric conformations (often an eclipsed conformation). 

This molecule s chirality is more apparent when drawn in its most symmetric conformation. Drawn flat, the two mirror-image structures of fraw,s-l,2-dibromocyclohexane are still non-superimposable. This compound is inherently chiral, and no conformational changes can interconvert the two enantiomers. 

The phenolic units of a calixarene can also become structurally different by the attachment of different alkyl or acyl residues to the oxygens, which may simultaneously lead to the necessary conformational restriction. A recent paper describes a rational way to synthesize tetraethers with four different O-alkyl groups in the cone conformation,118 which is outlined in Figure 12. The last four compounds in this sequence are inherently chiral.119... 

The possible number of inherently chiral structures and conformers further increases if the calixarene contains both different phenolic units and different bridges in the macrocyclic skeleton. For example, two chiral monoethers 88a,b are available from dihomooxacalix[4]arenes (one -CH2-0-CH2- bridge instead of -CH2-).17188b is the preferred product of the mono-O-alkylation, since the negative charge of the respective phenoxide anion is better stabilized by intramolecular hydrogen bonds due to the smaller distance between the phenoxide anion and the hydroxy groups. Tetraketone derivatives (Y = CH,-C(0)-R) in the two possible partial cone conformations, have been prepared in moderate yields. 

The generality of this new type of shape-activity correlation is demonstrated for five receptor/substrate systems trypsin/arylammonium inhibitors the D2-dop-amine receptor/dopamine derivative agonists trypsin/organophosphate inhibitors acetylcholinesterase/organophosphates and butyrylcholinesterase/organo-phosphates. The correlations were obtained both for active-site induced chiral conformers and for inherently chiral inhibitors. Interestingly, for some of these cases the correlation of activity with structure is hidden when classical parameters, such as chain length, are taken, but is revealed with this shape descriptor. 

Further evidence for the existence of a helical conformation for meta-linked CPEs comes from circular dichroism (CD) studies of j-PPE-C02 (Figure 14.10). The basis for this experiment lies in the fact that a helix is an inherently chiral structure. Because the helix is chiral, one would expect that if an enantiomeric excess (ee) of the right- or left-handed forms (the P and M forms) exists in solution, then the CD spectrum would feature a bisignate signal due to exciton coupling of the backbone chromophores which are in a chiral environment [35]. However, when a polymer folds into a helical structure, because the polymer itself is achiral, the ensemble of helically folded polymers exists as a... 

Often symmetry operations cannot be used in a simple way to classify chiral forms because, e.g., the molecule consists of a number of conformations. Therefore, independent of the symmetry considerations, a chemical approach to describe chiral molecules has been introduced by the use of structural elements such as chiral centers, chiral axis, and chiral planes. Examples for a chiral center are the asymmetric carbon atom, i.e., a carbon atom with four different substituents or the asymmetric nitrogen atom where a free electron pair can be one of the four different substituents. A chiral axis exists with a biphenyl (Figure 3.2) and chiral planes are found with cyclo-phane structures [17]. Chiral elements were introduced originally to classify the absolute configuration of molecules within the R, S nomenclature [16]. In cases where the molecules are chiral as a whole, so-called inherent dissymmetric molecules, special names have often been introduced atropiso-mers, i.e., molecules with hindered rotation about a helical molecules [18], calixarenes, cyclophanes [17], dendrimers [19], and others [20]. 

Besides dihomooxacalix[4]arenes bearing carbonyl groups at their lower rims (28-32) reported before 2000 [26, 27], 9a has been used to prepare the inherently chiral triethyl ester 33 [28] and the tetra(2-pyridyl) 34 [29] derivatives. Depending on the reaction conditions (use of 80 % NaH instead of 95 % NaH and less reaction time), partial 0-alkylation of 9a with 2-(chloromethyl)pyridine hydrochloride was also achieved by Marcos and coworkers [29]. Five of the eight possible partially alkylated compounds 35 (mono-substituted 35b and di-substituted 35c-f) were obtained in the cone conformation. Recently, the same group reported the preparation of a series of bidentate urea (36-41) and thiourea (42) derivatives in a four step synthesis from the parent compound 9a [30, 31]. Their structure determination in solution by NMR spectroscopy (and in the solid state for compounds 38 and 41 by single crystal X-ray crystallography) indicated the cone conformation for all the compounds. The cone tetraethyl ester 43 was also described [11]. 

The primary structure with alternate double bonds along the main chain was confirmed. Spectroscopic data (IR, NMR, and UV) show that conjugation is only partial, according to a non-planar conformation of the chains due to mutual steric repulsions of side chains in 2,3 relative positions. The CD spectra show, when compared to absorption spectra, a system of OA bands attributed to the presence of an inherently chiral polyene chromo-phore in the main chain and also related to a conformational equilibrium in solution. 

There are two different kinds of sources of molecular chirality central chirality and axial chirality (Fig. 1). Central chirality is due to the existence of chiral carbon, whereas axial chirality originates from twisted structures of molecules, between which a sufficiently high energy barrier exists, preventing the chiral conformational interconversion in ambient conditions. Surprisingly, however, the introduction of nonchiral molecules to chiral liquid crystalline environments sometimes enhances the chirality of the systems [3-5]. This means that inherently nonchiral molecules act as chiral molecules in chiral environments. This occurs in the following way. Molecules with axial chirality behave as nonchiral molecules when the potential barrier is low enough for chiral conformational interconversion. But when such... 

The area covered is very widespread and the role of the calixarene molecules reach from a simple platform or skeleton on which to assemble chiral centers to an inherent part of the chiral structure. Biologically active molecules or derivatives are involved as well as artificial ligands and their metal complexes. Chiral calixarenes have been used as stationary phases in analytical separations or as host molecules in sensors. Basic properties of calixarenes, such as their conformational stabilities, have been studied with chiral derivatives as well as more... 

Helicenes are polycyclic aromatic compounds in which the helical structure is a consequence of a steric repulsion of the terminal aromatic nuclei. The conformation and chirality of helicenes have attracted the attention of many researchers over the years [39]. We chose to enlist helicenes as both pawls and springs because (1) they have an inherent helicity that we thought would favor the unidirectional rotation and (2) their relatively rigid structures resist deformation. That resistance to deformation is also a characteristic of springs. 

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