Hydrogen bonding shuttles

These ideas have been illustrated in a recent study of the co-crystalline complex of 1-meCyt 5-FUra [19]. Using model calculations, it was shown how the hydrogen-bonding network of the crystal is able to sustain a proton shuttle which leads to the selective formation of certain radicals. Calculations predict that the site of reduction would be the cytosine base, yielding the N3 protonated cytosine anion, Cyt(N3-I-H), while the uracil base would be the site of oxidation, yielding the N1 deprotonated uracil cation, Ura(Nl—H) ... 

Interestingly, although the substrate is bound in the pocket in a water-free environment, there is a system of hydrogen bonds that can shuttle the proton from the bound alcohol to the surface (equation 16.4).17... 

Hannam, J. S., Kidd, T. J., Leigh, D. A., Wilson, A. J., Magic rod rotaxanes The hydrogen bond-directed synthesis of molecular shuttles under thermodynamic control. Org. Lett. 2003, 5, 1907-1910. 

Scheme 6.5.7. Light-driven shuttling of a rotaxane with internal hydrogen bonding.

Keeping in mind that all three x-rayed flavodoxins (7, 8, 9, 10, 11) exhibit C(7,8) as the only possible point of direct outer contact while all the rest of the flavin molecule is buried in the protein, we must finally admit that chemically C(8) is the reasonable site of orbital overlap between flavin and secondary heteroaromatic le -donor-acceptor molecules such as flavin itself and, above all, cytochrome. Flavodoxins represent the case of flavoproteins scheduled for le -only transfer by a hydrogen bond directed from the apoprotein towards N(5), stabilizing the radical Hp. The bond is strong enough to maintain the active protein reduced in the lower le -shuttle between Flred and Fl. 

Umehara T, Kawai H, Fujiwara K, Suzuki T (2008) Entropy- and hydrolytic-driven positional switching of macrocycle between imine- and hydrogen-bonding stations in rotaxane-based molecular shuttles. J Am Chem Soc 130 13981-13988... 

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