Temperature-Induced Reversible First-Order Single Crystal to Single Crystal Phase Transition in Boc‑γ⁴(<i>R</i>)Val-Val-OH: Interplay of Enthalpy and Entropy

Crystals of Boc-γ⁴(<i>R</i>)­Val-Val-OH undergo a reversible first-order single crystal to single crystal phase transition at <i>T</i>_c ≈ 205 K from the orthorhombic space group <i>P</i>22₁2₁ (<i>Z</i>′ = 1) to the monoclinic space group <i>P</i>2₁ (<i>Z</i>′ = 2) with a hysteresis of ∼2.1 K. The low-temperature monoclinic form is best described as a nonmerohedral twin with ∼50% contributions from its two components. The thermal behavior of the dipeptide crystals was characterized by differential scanning calorimetry experiments. Visual changes in birefringence of the sample during heating and cooling cycles on a hot-stage microscope with polarized light supported the phase transition. Variable-temperature unit cell check measurements from 300 to 100 K showed discontinuity in the volume and cell parameters near the transition temperature, supporting the first-order behavior. A detailed comparison of the room-temperature orthorhombic form with the low-temperature (100 K) monoclinic form revealed that the strong hydrogen-bonding motif is retained in both crystal systems, whereas the non-covalent interactions involving side chains of the dipeptide differ significantly, leading to a small change in molecular conformation in the monoclinic form as well as a small reorientation of the molecules along the <i>ac</i> plane. A rigid-body thermal motion analysis (translation, libration, screw; correlation of translation and libration) was performed to study the crystal entropy. The reversible nature of the phase transition is probably the result of an interplay between enthalpy and entropy: the low-temperature monoclinic form is enthalpically favored, whereas the room-temperature orthorhombic form is entropically favored

C₁₂ Helices in Long Hybrid (αγ)_<i>n</i> Peptides Composed Entirely of Unconstrained Residues with Proteinogenic Side Chains

Unconstrained γ⁴ amino acid residues derived by homologation of proteinogenic amino acids facilitate helical folding in hybrid (αγ)_<i>n</i> sequences. The C₁₂ helical conformation for the decapeptide, Boc-[Leu-γ⁴(<i>R</i>)­Val]₅-OMe, is established in crystals by X-ray diffraction. A regular C₁₂ helix is demonstrated by NMR studies of the 18 residue peptide, Boc-[Leu-γ⁴(<i>R</i>)­Val]₉-OMe, and a designed 16 residue (αγ)_<i>n</i> peptide, incorporating variable side chains. Unconstrained (αγ)_<i>n</i> peptides show an unexpectedly high propensity for helical folding in long polypeptide sequences

Temperature-Induced Reversible First-Order Single Crystal to Single Crystal Phase Transition in Boc‑γ⁴(<i>R</i>)Val-Val-OH: Interplay of Enthalpy and Entropy

Crystals of Boc-γ⁴(<i>R</i>)­Val-Val-OH undergo a reversible first-order single crystal to single crystal phase transition at <i>T</i>_c ≈ 205 K from the orthorhombic space group <i>P</i>22₁2₁ (<i>Z</i>′ = 1) to the monoclinic space group <i>P</i>2₁ (<i>Z</i>′ = 2) with a hysteresis of ∼2.1 K. The low-temperature monoclinic form is best described as a nonmerohedral twin with ∼50% contributions from its two components. The thermal behavior of the dipeptide crystals was characterized by differential scanning calorimetry experiments. Visual changes in birefringence of the sample during heating and cooling cycles on a hot-stage microscope with polarized light supported the phase transition. Variable-temperature unit cell check measurements from 300 to 100 K showed discontinuity in the volume and cell parameters near the transition temperature, supporting the first-order behavior. A detailed comparison of the room-temperature orthorhombic form with the low-temperature (100 K) monoclinic form revealed that the strong hydrogen-bonding motif is retained in both crystal systems, whereas the non-covalent interactions involving side chains of the dipeptide differ significantly, leading to a small change in molecular conformation in the monoclinic form as well as a small reorientation of the molecules along the <i>ac</i> plane. A rigid-body thermal motion analysis (translation, libration, screw; correlation of translation and libration) was performed to study the crystal entropy. The reversible nature of the phase transition is probably the result of an interplay between enthalpy and entropy: the low-temperature monoclinic form is enthalpically favored, whereas the room-temperature orthorhombic form is entropically favored

Unconstrained Homooligomeric γ‑Peptides Show High Propensity for C₁₄ Helix Formation

Monosubstituted γ⁴-residues (γ⁴Leu, γ⁴Ile, and γ⁴Val) form helices even in short homooligomeric sequences. C₁₄ helix formation is established by X-ray diffraction in homooligomeric (γ)_<i>n</i> tetra-, hexa- and decapeptide sequences demonstrating the high propensity of γ residues, with proteinogenic side chains, to adopt locally folded conformations