1.1. INTRODUCCIÓN
1.4.5. Variables que caracterizan el Clima
(4-3,4-3,5)12G2 was previously shown to be predisposed to columnar self-
assembly.95 In order to test the effect of chirality transfer (allosteric regulation) from the
apex to the dendron, Boc-L-Tyr-L-Ala-OMe and Boc-D-Tyr-D-Ala-OMe were attached to
(4-3,4-3,5)12G1-CH2OH via Mitsunobu coupling (Scheme 2.9).23, 72 NMR and CD/UV- vis experiments confirmed self-assembly into helical columnar architectures (Figure 2.37) in solvophobic solvents that preferentially solvate the aliphatic tails (d6-cyclohexane and cyclohexane, respectively). Remarkably, XRD in combination with TEM and STM indicated the formation of hollow helical columnar architectures (Figure 2.6cd,Figure 2.38). Helical porous self-assembly into columns that self-organize into a h is proposed
the dipeptides with the columnar axis (Figure 2.38). This model is similar to a -barrel. These structures functioned as aquaporin mimic, mediating water transport via a Grotthuss-type mechanism without eliminating H+ transport across artificial cell membranes such as liposomes102 or polymersomes103 (Figure 2.40). However, these
columns do not allow transport of Na+ , Li+ and Cl- ions. The transport of water across giant vesicular membranes containing dendritic-dipeptide channels was demonstrated through microscopy experiments in hypertonic and hypotonic solutions. Vesicles containing dendritic-dipeptides exhibited expansion of the vesicle in hypertonic solution and contraction in hypertonic solution, relative to the vesicles containing no channel, indicating that water is able to permeate the membrane only in the presence of the dendritic-dipeptides allowing for pressure regulation.102
Figure 2.38 - NMR (a) and CD/UV-vis (b, c, d) experiments confirming helical columnar self-assembly of dendronized dipepetides. Reprinted with permission from ref. 72. Copyright 2004 Macmillan Publishers Ltd: Nature.
Figure 2.39 -. Models of self-assembled helical porous columns from dendritic dipeptides (left, a-d), orientation of dipetide groups in the column (e) and hydrogen bonding network (right). Reprinted with permission from ref. 72. Copyright 2004 Macmillan Publishers Ltd: Nature.
Figure 2.40 - Proton Transport experiment comparing a liposome containing an
impermeable pH sensitive fluorescent indicator (left) and a liposome containing a self- assembled dendritic channel (right). Reprinted with permission from ref. 72. Copyright 2004 Macmillan Publishers Ltd: Nature.
It is useful to compare the self-assembly of the parent (4-3,4-3,5)12G1-OH with the corresponding dendritic dipeptide (4-3,4-3,5)12G2-CH2-Boc-L-Tyr-L-Ala-OMe.23 The parent dendron self-assembles into a supramolecular column with a columnar diameter of 52.6 Å and a negligible pore of <3 Å. Each stratum is composed of six dendrons with a projection of solid angle ’=60. The supramolecular columns self- organize in a h lattice. The dendritic dipeptide self-assembles into a porous helical
supramolecular columns with a diameter of 77.1 Å and pore diameter of 13.3 Å. Each column stratum is composed of approximately 11.6 dendrons with a projection of solid angle ’ = 31.0. The dendritic dipeptide enhances the overall column diameter thus supporting the stabilization of the pore via H-bonding, but also by decreasing the molecular taper angle of the dendron resulting in a lower projection of solid angle and more dendrons per stratum. Like the parent dendritic alcohol, the dendritic dipeptide self- organizes into a h lattice. For the dendritic dipeptide it was observed that periphery
aliphatic tail length increases the diameter of the column, while it decreases the size of the pore from 15.8 Å at n=6 to 11.7 Å at n =16. Interestingly, by decreasing the tail length in the parent dendritic alcohol from n=16 to n=1, the pore-size increases from <3Å to 6.8 Å. Thus, while the dipeptide does seem to support and enhance pore formation through, it is not a necessary condition.
The self-assembly of dendronized dipeptides into helical porous columns can be allosterically programmed by the protecting group on the dipeptide N-terminus.104 Decreasing the size of the protecting group from X= Boc to X = Moc to X=Ac results in a continual decrease in the H-bond length of the interior network, resulting in enhanced
thermal stability of the columnar phase. However, with the decrease in the size of group from the apex comes an increase in the molecular taper angle, a decrease in column size, number of dendrons per stratum, , and Dpore. Further in the case of X = Moc, Ac, helical
internal order is observed via XRD.
All four diastereomers of Boc-D/L-Tyr-D/L-Ala-OMe were prepared.105 It was
demonstrated that the helical sense of the self-assembled dendritic dipeptides is determined by the chirality of the Tyr residue that is directly attached to the dendron (Figure 2.41). Crude allosteric regulation is operating, wherein modulation of the chirality of the more distant Ala residue, also affects the finer features of self-assembly via subtle modulation of the hydrogen-bonding network and pore diameter. Specifically, homochiral dendronized dipeptides L-L/D-D exhibit different self-organized structures
than heterochiral dendronized dipeptides L-D and D-L.
Figure 2.41 - The self-assembly of homochiral and heterochiral dendritic dipeptides is stereochemically controlled and allosterically regulated by the stereochemistry of the dipeptide. Reprinted with permission from ref.105. Copyright 2005 Wiley-VCH Verlag GmbH & Co. KGaA.
The structure and dimensions of the internal pore is also allosterically regulated by substitution of the L-Ala residue with Gly, L-Val, L-Leu, L-Ile, L-Phe, or L-Pro.106 The
helical pore could be tailored from 9-15 Å. The largest structural distortion was observed in the case of L-Val at low temperature in which self-organization into r-c rather than h
lattice is observed. At elevated temperature the h phase emerges. This thermoreversible
shape change between ellipsoidal and circular columns was also observed for hybrid dendronized dipeptide (S)-(4-3,4-3,5-4)12G2-CH2-(Boc-L-Tyr- L-Ala-OMe) (Figure 2.42).86
Figure 2.42 - Thermoreversible shape change of circular to ellipsoidal columns as
evidenced by cross- sections of the reconstructed electron density maps. Reprinted with permission from ref.86. Copyright 2006 American Chemical Society.
It was shown that attachment of a dipeptide to the apex of a dendron predisposed to columnar self-assembly, (4-3,4-3,5)12G1-CH2OH, mediated the formation of helical porous columns. It was later demonstrated, that attachment to other column forming dendrons such as (4-3,4,5-3,5)12G1-CH2OH likewise resulted in porous helical columnar structures.107 Attachment of a dipeptide to the apex of a dendron predisposed to
spherical self-assembly (4-(3,4)2)12G2-CH2OH which is the constitutional isomer of (4- 3,4-3,5)12G2-CH2OH, was shown to mediate self-assembly into a chiral hollow sphere (Figure 2.43).87 In addition (4-(3,4)2)dm8*G2-CO2Me/CH2OH and (4-3,4-3,5-
4)dm8*G2-CO2Me/CH2OH were shown to self-assemble in chiral hollow spheres,
while (4-(3,4)2)12G2-CO2Me/CH2OH, (4-3,4-3,5-4)nG2-CH2OH (n=4, 6, 12) , and (4- 3,4-3,5-42)nG2-CH2OH ( n=4, 6, 8, 10, 12 ) were shown to self-assemble in non-chiral hollow spheres. Increasing the alkyl tail lengths was shown to diminish the diameter of the hollow core.
Figure 2.43 - Self-assembly of (4-(3,4)2)12G2-CH2-Boc-L-Tyr-L-Ala-OMe in an apple- peel, spherical helix or loxodrome around a hollow core. Reprinted with permission from ref. 87. Copyright 2008 American Chemical Society.