Helix aggregation in peptide crystals: Occurrence of either all parallel or antiparallel packing motifs for α‐helices in polymorphs of Boc‐Aib‐Ala‐Leu‐Ala‐Leu‐Aib‐Leu‐Ala‐Leu‐Aib‐OMe

AbstractThree crystalline polymorphs of the helical decapeptide, Boc‐Aib‐Ala‐Leu‐Ala‐Leu‐Aib‐Leu‐Ala‐Leu‐Aib‐OMe, have been obtained. Antiparallel helix aggregation is observed in crystals grown from methanol (A), while completely parallel packing is observed in crystals from isopropanol (B) or an ethylene glycol‐ethanol mixture (C). Crystals B and C are very similar in molecular conformation and packing. The packing motifs in crystals A and B consist of rows of parallel molecules, with an almost identical arrangement in both crystals. In crystal A, adjacent rows assemble with helix axes pointed in oppsite directions, whereas in crystal B all rows assemble with helix axes pointed in the same direction. Electrostatic interactions between helix dipoles do not appear to be a major determinant of packing modes. The structures also do not provide a ready rationalization of packing preferences in terms of side‐chain interactions or solvation. The α‐helix of the peptide in crystal A has seven 5 → 1 hydrogen bonds; the helix in crystal B is a mixed 310/α‐helix. The crystal parameters are as follows. Crystal A: C51H92N10O13·CH3OH, space group P21 with a = 10.498(1) Å, b = 18.189(3) Å, c = 16.475(3) Å, β = 99.28(1)°, Z = 2, R = 9.6% for 1860 data. Crystal B: C51H92N10O13·C3H7OH, space group P21 with a = 10.534(1) Å, b = 28.571(4) Å, c = 11.055(2) Å, β = 95.74(1)°, Z = 2, R = 6.5% for 3251 data. Crystal C: C51H92N10O13·C2H5OH, space group P21, with a = 10.450(1) Å, b = 28.442(5) Å, c = 11.020(2) Å, β = 95.44(1)°, Z = 2, R = 14.8% (isotropic) for 1948 data.