Factoring chirality

Yang, C., Zhong, C. Chirality factors and their application to QSAR studies of chiral molecules. QSAR Comb. Sci. 2005, 24, 1047-1055. 

Asymmetric induction and stereoregularity can be treated, at least in part, as two distinct phenomena however, it has been observed that the values of pu and Pol can be divided into two parts one dependent on chiral factors external to the chain (catalyst, environment, etc.) and the other dependent on the intramolecular chain induction. This latter is a factor of stereoregularity or cooper-ativity rather than of chirality (its value is identical for both the DD and LL successions) (328). Both factors can be expressed as differences of free energies of activation In favorable cases, when they are of the same sign, asymmetric polymerization becomes easier (i.e., under the same conditions it gives a higher optical yield) than an analogous nonmacromolecular asymmetric synthesis. 

D. Asymmetric Autocatalysis using Circularly Polarized Light as a Sole Chiral Factor... 

In the absence of any chiral factors, the probability of the formation of S- and 77-enantiomers is 1 to 1. However, the numbers of the resulting two enantiomers are not exactly the same in almost all cases. Mislow197 described the inevitability of small enantiomeric enrichment in absolute asymmetric synthesis. According to the statistics, it is expected that a fluctuation in the ratio of the S- and 77-enantiomers becomes more and more likely as the numbers in the enantiomer mixture become smaller198. Thus, if the asymmetric autocatalysis is initiated without adding any chiral substance, small fluctuations of enantiomers produced in the initial stage could be enhanced by consecutive asymmetric autocatalytic reaction of pyrimidyl alkanol with amplification of chirality. 

The importance of chiral factors in disposition and toxicity has been fully recognized only relatively recently, although important examples have been known for some time. For instance the S(—) enantiomer of thalidomide is known to have greater embryotoxicity than the R(+) enantiomer (see chap. 7). Another example in which a particular isomer of a metabolite is responsible for a carcinogenic effect is the exo-oxide of aflatoxin Bi, discussed later in this chapter (Fig 5.14). 

Still another DA receptor model, based on the study of aporphines, takes chirality factors into consideration. This model suggested by Neumeyer (16, 96) postulates an obstruction or "obstacle" on the receptor that precludes appropriate interaction of aporphines in the 6aJ> configuration with the receptor. This model, in common with many others, also takes into account OH binding sites, conformational aspects, steric hindrance factors, and N-substitution with the observation as noted elsewhere (e.g., 97), that N-substitution with groups as large as propyl may provide supplemental binding to favor D-2 receptor interaction. As the asymmetric center of apomophine is located on the carbon ct to the N, whereas in I-III it is located on the ben-... 

On the other hand, the IOM samples from which several percent amounts of organic compounds had been removed by hydrothermolytic treatment (IOM-H) gave results that are in sharp contrast to the above-mentioned meteoritic sample. Here, both (R)- and (S)-pyrimidyl alkanol 12 were obtained equally and indicate the absence of chiral factors in the IOM-H sample, i.e., the results are stochastic. Similar stochastic results were obtained on conducting the asymmetric autocatalysis in the presence of Murchison powders from which all the organic material had been removed by exposure to oxygen plasma. 

Highly sensitive chiral discrimination of amino acids with low ee was described. Amino acids with low ee act as a chiral initiator of asymmetric autocatalysis. In the presence of amino acids with low ee, pyrimidine-5-carbaldehyde was treated with z-P Zn to produce chiral pyrimidyl alkanol with the absolute configuration correlated with that of the amino acid by the consecutive asymmetric autocatalysis with amplification of ee. In addition, direct examination of extraterrestrial chirality was performed using meteorites by applying the asymmetric autocatalysis as the chiral sensor. The results indicated the presence of some chiral factor in the meteorites other than known organic compounds such as amino acids. 

One of the main features of asymmetric autocatalysis and the formation of the helix is that the initial extremely low enantioenrichment is amplified significantly to near enantiopure. These processes of amplification of chirality have become powerful tools to elucidate the origin of chirality of organic compounds. For example, by using asymmetric auto catalysis, spontaneous absolute asymmetric synthesis without the intervention of any chiral factor has been realized. 

The physico-chemical parameters of the chemical stimuli which have been shown to have relevance and to be interrelated to the sensory response it elicits as specific odor or taste, are the factors controlling concentration at the receptor areas (solubility, hydrophilicity, lipophilicity, volatility, and partition coefficients), molecular features (size, shape, stereochemical and chirality factors and functional groups), and electronic features (polarity and dipoles) controlling positioning and contact at receptor surfaces (53). Many of these physico-chemical data are not available for many of the chemical stimulants, and till they are gathered, structure-response studies will be much restricted. The effects of interactions of the above parameters appear to a larger degree in the perception of odor, the dimensions of which are many and complex viz. nuances, composite... 

The measured crystal optical activity, in general, can be either of molecular origin or due to the chiral helical arrangement of chiral or achiral molecules in the crystal, or both. The two factors are difficult to separate. Kobayashi defined a chirality factor r = (pc — ps)/pc = 1 — pslpc, where pc is the rotatory power per molecule of a randomly oriented crystal aggregate derived from the gyration tensors determined by HAUP, and ps that in solution [51]. It is a measure of the 4 crystal lattice structural contribution to the optical activity and represents the severity of the crystal lattice structural contribution to the optical activity, and represents the severity of the restriction of the freedom of molecular orientation by forming a crystal lattice. Quartz is a typical example of r = 1, as it does not contain chiral molecules or ions and its optical activity vanishes in random orientation (ps = 0). 

Optical activity in solution, unlike the same effect in crystals, is an isotropic effect. This interaction between a polarized photon and a molecule therefore implicates a chiral factor that is independent of direction, such as the molecular wave function, and in particular, its complex phase. It is a non-classical factor and hence cannot be attributed directly to a classical three-dimensional structure. In a crystal where optical activity arises from three-dimensional... 

CHGD index charged partial surface area descriptors chiral factors -> weighted matrices chirality descriptors... 

Point Chirality Factors that Introduce Asymmetry in the (R,R)-Tartaric Acid Adsorbed Motif... 

The idea of modifying graph invariants to make them chirality sensitive was proposed by Schultz et al. in 1992 [Schultz, Schultz et al, 1995], introducing a chiral factor equal to + 1 or-1 for any atom in R- or S-configuration, respectively, and assigning a value of 0 to all the other atoms. 

MARCH-INSIDE descriptors are derived from the different kth powers of the electron-transition stochastic matrix, denoted as H, which is a stochastic matrix of dimension Ax A derived from the —> dectronegativity-weighted a acency matrix A, modified by a 3D central chirality factor to [Gonzalez Diaz, Sanchez et al., 2003], as... 

The importance of chiral factors in disposition and toxicity has been fully recognized only relatively... 

Figure 17.18 (p. 54) depicts transformations 71-72 where account is taken of the chiral influence (chiral solvent, chiral catalyst, "chiral" radiation or other chiral factor). In these... 

Soai et al repeated these reactions without adding an asymmetric inductor carrying out 37 separate runs rather then successive reactions as in Singleton s experiments, and they obtained both R- and S -products, showing almost stochastic distribution S -products were formed 19 times and R-products 18 times, with ee values of up to 91 %. The small deviation from stochastic distribution was. due to unknown chiral factors... 

Spontaneous absolute asymmetric synthesis, that is, the formation of enantioenriched compound without the intervention of any chiral factors, has been proposed as one of the origins of biological homochirality in nature [29, 46, 47]. It has been weU... 

As mentioned in the preceding section, the significant amplification of enantiomeric purity from a small value can be achieved by asymmetric autocatalysis of pyrimidyl alkanol. Thus, if the enantioenrichment of the initially formed asymmetric autocatalyst could be introduced by a discrete chiral factor, we can expect to obtain pyrimidyl alkanol with a detectable ee by the asymmetric autocatalytic amplification of ee. The sense of the ee should be controlled by the configuration of the originally used external chiral factor. We have examined the discrimination of a tiny chirality by using asymmetric autocatalysis. 

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