Spacer skeletons

R. A. Lewis and P. M. Dean, Proc. R. Soc. London Ser. B, 236, 125 (1989). Automated Site-Directed Drug Design The Concept of Spacer Skeletons for Primary Structure Generation. 

Figure 7 Example of spacer skeleton. Reproduced with permission. See Ref. 88.

In polar solvents, the structure of the acridine 13 involves some zwitterionic character 13 a [Eq. (7)] and the interior of the cleft becomes an intensely polar microenvironment. On the periphery of the molecule a heavy lipophilic coating is provided by the hydrocarbon skeleton and methyl groups. A third domain, the large, flat aromatic surface is exposed by the acridine spacer unit. This unusual combination of ionic, hydrophobic and stacking opportunities endows these molecules with the ability to interact with the zwitterionic forms of amino acids which exist at neutral pH 24). For example, the acridine diacids can extract zwitterionic phenylalanine from water into chloroform, andNMR evidence indicates the formation of 2 1 complexes 39 such as were previously described for other P-phenyl-ethylammonium salts. Similar behavior is seen with tryptophan 40 and tyrosine methyl ether 41. The structures lacking well-placed aromatics such as leucine or methionine are not extracted to measureable degrees under these conditions. 

Figure 3. Half-shell structure model for organosilicon compounds with different spacers along the C3 symmetric substituent axis and dihedral angles go(X3Y-YX3) determined for the molecular skeletons.

The structural comparison of the C3-symmetric skeletons of the organosilicon (halfshell (spacer) half-shell) molecules (Figure 8a) provides a rational criterion for steric overcrowdedness Obviously, at distances Y Y below 333 pm different dihedral angles a)(Xo,Y YX3) between the half-shell substituents are observed, whereas above 414 pm they are identical. The accompanying torsion D3d — D3 within the molecular skeleton is therefore a criterion for steric overcrowding48. 

The resorcarene 23a, on the other hand, was obtained by O-alkylation of the corresponding octol. Its incorporation in a dimethylpolysiloxane backbone led to a stationary phase by which proteinogenic amino acids could be separated into their enantiomers by GC of their 7V(0,S)-trifluoroacetylmethylesters with separation factors aLD = 1.025-1.102.50 The question remains in this case (and in similar cases), whether the chiral amide functions have to be attached to the resorcarene skeleton, or if a direct attachment to the polymer backbone via suitable spacers would lead to similar results. The chiral resorcarene octaamides 23b prepared by... 

A probe for identifying an ABA receptor can be designed by building a functional group in the ABA skeleton or linking it via an appropriate spacer, with the notion of instilling an affinity for the receptor or easily detecting the captured receptor. 

Pancuronium and vecuronium (Fig. 11.39) were designed to act like tubocurarine, but with a steroid nucleus acting as the spacer . The distance between the quaternary nitrogens is 1.1 nm as compared to 1.4 nm in tubocurarine. Acyl groups were also added to introduce two acetylcholine skeletons into the molecule in order to improve affinity for the receptor sites. These compounds have a rapid onset of action and do not affect blood pressure. However, they are not as rapid in onset as suxamethonium and also last too long (45 minutes). 

Shipps and Rebek have designed a new cleft (cf. Figure 79) based on two xanthene skeletons separated by a porphyrin spacer unit (Figure 28) [41]. They demonstrated a high (>1O5M ) binding constant with 1,4-diazabicy-clo[2.2.2]octane (DABCO) in chloroform. 

During reconstruction of the Statue of Liberty, Teflon spacers were placed between the iron skeleton and the copper plates that cover the statue. What purpose do these spacers serve ... 

In synkinesis steroids are useful in solution as spacers between two reactive. sites bound to steroid substituents and as matrices on solid. surfaces. The magic of the steroidal skeleton lies in its extreme variability of stiffness and flexibility accompanied by consistent intramolecular distances (Fig. 3.1.1). Steroids also form hydrophobic and amphiphilic domains with pronounced stereochemical control and selective solubility in membrane structures. 

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