Conformational memory effect

Rychnovsky et al. considered the formation of achiral conformers from chiral molecules and trapping the prochiral radical with a hydrogen atom donor based on memory of chirality (Scheme 12) [41], The photo-decarboxylation of optically active tetrahydropyran 40 leads to an intermediate 43, which now does not contain a stereocenter. If the intermediate 43 can be trapped by some hydrogen atom source before ring inversion takes place, then an optically active product 41 will be formed. This is an example of conformational memory effect in a radical reaction. It was reported that the radical inversion barrier is low (< 0.5 kcal/mol) while the energy for chair flip 43 44 is higher (5 to... 

Griesbeck, A. G., Mauder, H., Stadtmuller, S., Intersystem Crossing in Triplet 1,4 Biradicals Conformational Memory Effects on the Stereoselectivity of Photocycloaddition Reactions, Acc. Chem. Res. 1994, 27, 70 75. 

The mechanistic rationalization of the highly exo-selective formation of oxetanes has been exempHfied by Griesbeck et al. The idea was originally used for rationalization of the endo-selectivity in the reaction with 2,three-dimensionalihydrofuran derivatives (Scheme 10). " Namely, the stereochemical outcome is proposed to come from the relative stabihty of the intermediary triplet 1,4 diradicals (T-1,4-DR), whose conformations are suitable for the spin-orbit coupling (SOC) induced intersystem crossing (ISC) process. The Conformational Memory Effects (Griesbeck Model) in the stereoselectivity can be appH-cable to the stereochemical outcome for the reaction with furan (Scheme 11). 

Griesbeck, A. G. and StadtmuUer, S., Electronic control of stereoselectivity in photocycloaddition reactions. 4. Effects of methyl substituents at the donor olefin, /. Am Chem. Soc., 113,6923, 1991. Griesbeck, A. G., Mauder, H., and StadtmuUer, S., Intersystem crossing in triplet 1,4-biradicals conformational memory effects on the stereoselectivity of photocycloaddition reactions, Acc. Chem. Res., 27, 70, 1994. 

Apparently, this is due to some memory effect the core, which existed in the parent globular conformation (Fig. lb), was simply reproduced upon refolding caused by the attraction between H units. One may say that the features of the parent conformation are inherited by the protein-like copolymer. Looking at the conformations of Fig. 3, it is natural to argue that proteinlike copolymer globules could be soluble in water and thus they are open to... 

In certain cases, seemingly simple enolates can have a chiral memory effect . For example, treatment of a-imino lactam (5)-88 with f-BuOK in CD3OD for 6-13 days at 25°C gave the corresponding enantiomerically deuteriated a-imino lactam l-d-(S)-89 in quantitative yield with 98% D incorporation and ee 97% (equation 15) , via a conformationally chiral enolate. This methodology has been extended towards enan-tioselective alkylation of enolates. Excellent levels of enantioselectivity (ee 88%) were achieved for a-imino lactam (S)-SS using KHMDS as Brpnsted base and benzyl iodide as the electrophile . Interestingly, to prevent unwanted racemization of the intermediate enolate, the reaction time for deprotonation was lowered to 10 seconds, and to ensure rapid alkylation, 20 equivalents of Bnl were used . 

E-fS ES ES. The standard deviation of the distribution, (Atopen ) = 8.3 2ms, reflects the distribution bandwidth. For the individual T4 lysozyme molecules examined under the same enz unatic reaction conditions, we found that the first and second moments of the single-molecule topen distributions are homogeneous, within the error bars. The hinge-bending motion allows sufficient structural flexibility for the enzyme to optimize its domain conformation the donor fluorescence essentially reaches the same intensity in each turnover, reflecting the domain conformation reoccurrence. The distribution with a defined first moment and second moment shows typical oscillatory conformational motions. The nonequilibrium conformational motions in forming the active enzymatic reaction intermediate states intrinsically define a recurrence of the essentially similar potential surface for the enzymatic reaction to occur, which represents a memory effect in the enzymatic reaction conformational dynamics [12,41,42]. 

To further analyze the memory effect and the identification of multiple conformational intermediate states involved in the enz3miatic conformational motions, we have simulated the t. 

Fig. 24.8. Computational simulation analysis of conformational dynamics in T4 lysozyme enzymatic reaction, (a) Histograms of fopen calculated from a simulated single-molecule conformational change trajectory, assuming a multiple consecutive Poisson rate processes representing multiple ramdom walk steps, (b) Two-dimensional joint probability distributions <5 (tj, Tj+i) of adjacent pair fopen times. The distribution <5(ri, Ti+i) shows clearly a characteristic diagonal feature of memory effect in the topen, reflecting that a long topen time tends to be followed by a long one and a short fopen time tends to be followed by a short one...

Neumann [2] first used the term molecular hysteresis to describe the phenomenon which was hysteresis on precipitation and dissolution of the polymers in pH changes of aqueous solutions. However, because segments of the molecules interact, as do molecules in condensed form, the hysteresis he describes is still a collective phenomenon. Frieden [3] proposed the idea of a hysteretic enzyme in 1970 and Hand and Carpenter [4] reported that phosphofructokinase, an important regulatory enzyme, could be a hysteretic enzyme. The concept is of a simple mechanism consisting of two parts fast binding between the enzyme and a substrate, and a slow conformational change in the complex enzyme. The resulting conformation is retained for a considerable time, behavior that constitutes a memory effect but not hysteresis. 

There is a lot to explain here. It looks very odd that syn-66 is preferred and even more so that alkylation of the enolate 67 occurs on the same face as the undoubtedly large /-butyl group. Both these issues matter as the original chiral centre in proline is destroyed in 67 and only the newly introduced chiral centre in 66 retains the stereochemical information from proline. This centre acts as a relay for the stereochemical information. Others call this a memory effect. The acid-catalysed formation of the N, O-acetal 66 is under thermodynamic control (acetal formation is reversible) and the conformation 66a shows that the molecule folds about the necessarily cis ring junction and the /-butyl group prefers to be on the outside (or exo- face).8 The enolate 67 has a flattened conformation 67a (probably more flattened than this ) and its alkylation is under kinetic control. Attack is preferred on the outside, exo-face. Note that this happens to restore the original configuration at the ex-proline chiral centre. 

It was observed that a high proportion of template (10%) can be introduced without losing the mesomorphic order [ 199]. Moreover after template extraction, the polymorphism was quite different from that of the non-imprinted material, the variations depending on the structure of the template used and on its concentration [200]. The last point is the manifestation of a significant memory effect of the template, imprinted inside the mesomorphic structure. It arises from the interactions between template and the other parts of the network which can induce conformational constraints inside the networks during cross-linking. It occurs even though the amount of crosslinker is low (5%). Moreover, this point constitutes a means for the direct study of the imprint left in the network by the template. 

A study of the memory effect , the phenomenon that makes EB-1 transform into ES-I and EB-11 into ES-11 upon doping, and reversibly so, has been undertaken as well [305]. RDF analysis reveals differences between EB-1 and EB-11 in the range 2.5 A, i.e. in intrachain coiTelations. This is attributed to differences in chain conformation. (Ring tilt angles and C—N—C zigzag... 

---