Unfavorable interactions

The effect of the bond dipole associated with electron-withdrawing groups can also be expressed in terms of its interaction with the cationic u-complex. The atoms with the highest coefficients in the LUMO 3 are the most positive. The unfavorable interaction of the bond dipole will therefore be greatest at these positions. This effect operates with substituents such as carbonyl, cyano, and nitro groups. With ether and amino substituents, the unfavorable dipole interaction is overwhelmed by the stabilizing effect of the lone-pair electrons stabilizing 3. 

Bond orders, charges on the atoms in 1 l//-pyrido[2,l-Z)]quinazolin-l 1-one and its protonated form were calculated by quantum chemical calculations by the semiempirical AMI method. According to the results, the equilibrium conformation of the ring in 1 l//-pyrido[2,l-Z)]quinazolin-l 1-one is planar, while l//-pyrimido[l,2-u]quinolin-1-one adopts a conformation close to a half-chair due to the unfavorable interactions between the oxygen atom of the carbonyl group and the ring C-10 atom in the pen-position (97MI22). 

For small substituents X on the enolate the preference for A and C is diminished due to reduced unfavorable interactions of X. 

Moving OH from 4- to 2-position slightly reduces the acidity for X = S or CH2, but increases it for X = SO, the pKu values (in 48% aqueous ethanol) being 9.17 and 9.04 respectively. This was attributed to the above interaction. On the other hand, moving OH from 4- to 2-position greatly reduces the acidity of the sulfone system (pKa values 8.69 and 9.10 respectively) and this was attributed to an inescapable unfavorable interaction of the negative oxygens of S02 with the O- in the anion. 

Consistent with the unfavorable interactions is the fact that the dimethyl derivative 74 failed to undergo the intramolecular cycloaddition since in this case one of the Me groups would necessarily interfere in the transition state for cyclization. 

In summary, one can state that s-p-hybridization on the heavier main group metals is not responsible for the stereochemical activity of a lone pair. Instead, the general conclusion can be drawn that anti-bonding metal ns-ligand np interactions lead to structural distortions in order to minimize these unfavorable interactions. 

Hydrophobic interaction refers to the tendency of nonpolar compounds to self-associate in an aqueous environment. This self-association is driven neither by mutual attraction nor by what are sometimes incorrectly referred to as hydrophobic bonds. Self-association arises from the need to minimize energetically unfavorable interactions between nonpolar groups and water. 

Another type of steric effect results from interactions between diene substituents. Adoption of the s-cis conformation of the diene in the TS brings the d.v-oricnlcd 1- and 4-substituents on a diene close together. /(-1,3-Pcnladicnc is 103 times more reactive than 4-methyl-l,3-pentadiene toward the very reactive dienophile tetracyanoethylene. This is because the unfavorable interaction between the additional methyl substituent and the C(l) hydrogen in the s-cis conformation raises the energy of the TS.20... 

The difference in activity of the E and Z olefins against HRV-14 was explained by examining the relatively low energy virus-bound conformations. The result of an overlay of WIN-54954 (based on x-ray crystallography data), minimize E- and Z-olefinic structures and the butyne analogue, suggested that the E isomer showed a reasonable fit while the Z isomer did not. Furthermore, when the Z isomer was inserted into the HRV-14 pocket, unfavorable interactions occurred. 

FIGURE 10.14 Schematic drawing showing the localization of xanthophyll molecules in the cholesterol-rich (raft or DRM) domain and the cholesterol-poor (bulk or DSM) domain. Unfavorable interaction with cholesterol in the cholesterol-rich domain is indicated. 

It s a miracle that we re here at all. Most proteins are not very stable even though there are a large number of very favorable interactions that can be seen in the three-dimensional structure. The reason is that the favorable interactions are almost completely balanced by unfavorable interactions that occur when the protein folds. A reasonably small net protein stability results from a small net difference between two large numbers. There are lots of favorable interactions but also lots of unfavorable interactions. 

Don t get the impression that proteins need to be as stable as possible and that the unfavorable interactions are necessarily bad. Proteins shouldn t live forever. A good bit of metabolism is regulated by increasing and decreasing the amount of a specific enzyme or protein that is available to catalyze a specific reaction. If a protein were too stable, it might not be possible to get rid of it when necessary. 

The observed /rtrimethyl-silyl group and the allenyl group (Scheme 72). 

High oxidation state alkylidene complexes in which a heteroatom is bound to the alkylidene carbon atom are extremely rare [41]. Since the approach shown in Eq. 43 failed, the related approach shown in Eq. 44 was taken to prepare the medium-sized ring subunits [222]. The latter product was formed in good yield when n=2, R H, R2=Et, but only poor yield when n=2, R =Et, R2=H, possibly due to unfavorable interactions between the ethyl substituent and transannular groups in the transition state for cyclization of the allyl ether [222]. Ruthenium catalysts either failed or gave low yields, presumably because of the steric hindrance associated with ring-closing dienes of this type. 

In reactions in which methyl acrylate is used as the dienophile (Scheme 6.33), cycloadditions occur with lower levels of enantioselection (23% ee, as compared to 53 % observed for acrolein), but with significantly higher degrees of diastereoselectivity (17 1, endo-.exo). Improved levels of endo selectivity are observed in the case of the methyl ester (Scheme 6.33) this is perhaps because, at least in part, the dienophile p-system is oriented towards the t-butoxy ligand, where the steric influence of the bulky substituent is expected to be more pronounced. As before, formation of the endo isomer may occur to a greater extent, since the transition structure that leads to the exo isomer would involve energetically unfavorable interactions between the diene... 

Abe and co-workers [89] worked on the spiro-oxazine system NOSI6 shown in Scheme 13 and found markedly different ring-closure kinetics. Note that in the case of Abe and co-workers compound NOSI6, there are no unfavorable interactions between the proton on the naphthalene and the methine proton in either the TTT and CTT forms. In fact, TTT and CTT should be the most planar forms. Compare that to the case of the NOSH merocyanine, which was studied using H-NOE and found to be an equilibrium mixture of TTC and CTC [88]. Ring closure would clearly be a more favorable series of rotations to form the closed-form geometry for CTC and TTC than it would be for CTT and TTT. 

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