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of the matrix to CO2 was proven by adsorption isotherms and
by direct 1D and 2D MAS NMR detection.
The synthesis of the ten dipeptides (1–10) is reported in
the Supporting Information. Single crystals were obtained by
gel crystallization vapor diffusion techniques (acetonitrile
vapors). XRD data collection at 105 K was followed by
structure solution in space group P61 with Z = 6 (Z’ = 1). The
structures of 1–10, exemplified by Abu-Abu (1) in Figure 1,
are sustained by a unique hydrogen-bonding pattern with left-
handed double helices of head-to-tail chains with three-fold
screw symmetry. Amino···carbonyl interactions link the helix
strands, while hydrogen bonds to the carboxylate groups form
connections to three neighboring double helices, thereby
generating a robust supramolecular network. Abu-Leu (4)
and Nva-Leu (9) are somewhat unexpected members of this
family; Ala-Leu was obtained as a nonporous hemihydrate,[11]
and we had previously postulated that dipeptides containing
Leu residues are incompatible with Val-Ala class P61
symmetry owing to steric conflict.[2a] We now note that the
assumed short intermolecular H···H distances can be allevi-
ated by small changes in the main-chain and side-chain
torsion angles.
The crystal channels (Figure 2) exhibit the shape of right-
handed helices, with their grooves shaped by the terminal
methyl groups of the peptide side chains. Abu-Abu (1) forms
pores with a diameter of about 5.1 and has a void volume of
307 3 (17.4% of the unit-cell volume), which is comparable
to or higher than that of the channels of Val-Ala[5] and Ala-
Val.[6]
Figure 2. a) Channel-like pore volumes of the 1–10 crystals as explored
by a sphere of 1.2 radius (1.0 for 10) and 0.5 grid spacing. To
the right of the channels, the corresponding cross-sections are
reported (). b) Correlation between side-chain bulkiness and pore
diameter for the seventeen members of the Val-Ala class. Compounds
representing extreme values within each group are indicated.
The 3.3 pore size of Abu-Ile (5) is, surprisingly, smaller
than the 3.7 of Val-Ile.[2c] This observation may seem
counterintuitive, since a Val residue contains an additional
methyl group, but it reflects the substantial increase in unit-
3
3
cell volume, from 1840.5(6) for 5 to 1940.8(4) for Val-
Ile. For the corresponding pair Abu-Val (3) and Val-Val, the
channel diameter remains unchanged at 4.4 . The side chain
of the N-terminal Nva of peptides 6–10 has an extra methyl
group compared to the N-terminal Abu for 1–5, thus resulting
in a substantial reduction in channel diameters. Nva-Ile (10)
shows the smallest cross-section of all of the dipeptides: 2.3
(the pore size is so small that the channels are hardly explored
by any atom or molecule). Overall, there is an inverse
correlation between side-chain bulkiness and the channel
diameter, but with substantial variations depending on the
specific residues involved (Figure 2). The crystal packing
arrangements of peptides 1–10 have remarkably low density:
among the compounds with formula C8H16N2O3, Abu-Abu (1)
displays a crystal density as low as 1.06 gcmÀ3, which is
comparable to the benchmark of the family l-Val-l-Ala
(1.04 gcmÀ3 at 120 K).[5] Furthermore, no guests occluding the
channels were found by either 1H or 13C fast-MAS NMR, thus
demonstrating that the channels are empty.
17 dipeptides prepared so far, as well as eight potential, as yet
uninvestigated, members of the Val-Ala class. The results of
this investigation (see the Supporting Information) confirm
that in the P61 space group, five out of the seven previous
members of the Val-Ala class, including Val-Ala itself, are
conformationally locked with respect to side-chain orienta-
tions. By contrast, Abu-Abu (1) and Nva-Abu (6) can explore
five combinations of N- and C-terminal side-chain orienta-
tions. The channel shapes are consequently not fixed as in
Figure 2a; the absorption of large guests may trigger con-
version to other conformations. In this manner Abu-Abu
channels may reach diameters close to 6 .
A special feature of peptides 6–10 is that the side chains of
the N-terminal Nva residues cannot all adopt the preferred
2
conformations with c1 = trans,[1c] since this would lead to
prohibitively short intermolecular contacts at the center of
the channels. The side chains are instead systematically
disordered over alternating trans and gauche arrangements,
thus resulting in local three-fold screw symmetry (Figure 3a).
For calculations of void volumes, these structures were also
refined (to higher R-factors) in the trigonal space group P31
(with Z’ = 2).
The regular dipeptides of the Val-Ala class incorporate
Val and Ile residues with branched side chains of limited
conformational freedom. The more unrestricted ethyl and
propyl side chains of Abu and Nva suggest that a diversity of
side-chain conformations may be adopted, resulting in a soft
aliphatic layer lining the channel walls. This feature was
addressed by a comprehensive conformational analysis of all
13C Solid-state MAS NMR spectroscopy is very sensitive
to conformations and motional behavior of alkyl chains, and
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2015, 54, 15684 –15688