Chirality-controlled spontaneous twisting of crystals due to thermal topochemical reaction

Abstract

Crystals that show mechanical response against various stimuli are of great interest. These stimuli induce polymorphic transitions, isomerizations, or chemical reactions in the crystal and the strain generated between the daughter and parent domains is transcribed into mechanical response. We observed that the crystals of modified dipeptide LL (N₃-l-Ala-l-Val-NHCH₂C≡CH) undergo spontaneous twisting to form right-handed twisted crystals not only at room temperature but also at 0 °C over time. Using various spectroscopic techniques, we have established that the twisting is due to the spontaneous topochemical azide-alkyne cycloaddition (TAAC) reaction at room temperature or lower temperatures. The rate of twisting can be increased by heating, exploiting the faster kinetics of the TAAC reaction at higher temperatures. To address the role of molecular chirality in the direction of twisting the enantiomer of dipeptide LL, N₃-d-Ala-d-Val-NHCH₂C≡CH (DD), was synthesized and topochemical reactivity and mechanoresponse of its crystals were studied. We have found that dipeptide DD not only underwent TAAC reaction, giving 1,4-triazole-linked pseudopolypeptides of d-amino acids, but also underwent twisting with opposite handedness (left-handed twisting), establishing the role of molecular chirality in controlling the direction of mechanoresponse. This paper reports (i) a mechanical response due to a thermal reaction and (ii) a spontaneous mechanical response in crystals and (iii) explains the role of molecular chirality in the handedness of the macroscopic mechanical response.

Keywords: chirality; mechanoresponsive crystals; spontaneous; topochemical reactions; twisting.

Fig. 1.

Crystal-to-crystal topochemical oligomerization of dipeptide LL to triazole-linked oligopeptides.

Fig. 2.

Photographs of crystals of dipeptide LL (A) after storage at rt for 1 mo, showing twisted morphology (scale bar: 1 mm) and (B) after storage at 0 °C for 3 mo (scale bar: 200 µm). Optical microscopic image of the crystals of dipeptide LL (C) before (scale bar: 200 µm) and (D) after TAAC at 85 °C for 3 d (scale bar: 200 µm). (E) Hot-stage polarizing microscopic images of crystals during heating from 35 °C to 150 °C showing gradual twisting. (Scale bar: 500 µm.)

Fig. 3.

(A) Photograph of the LL crystal and face indices before twisting of the crystal (0.250 mm × 0.080 mm × 0.030 mm). (B) Appearance of the crystal (0.250 mm × 0.080 mm × 0.030 mm) after heating at 85 °C for 30 min on the goniometer. (C) Representation of a long rectangular plate-like crystal with various planes. Directions of TAAC reaction (c) and β-sheet formation (b) are also shown. (D) Schematic representation of generation of asymmetric distribution of product and reactant domains (layers) due to the nonuniform thermal stimuli and subsequent twisting. The triazole motif is color-coded as a violet pentagon, unreacted azide as a green arrowhead, and alkyne as red arrow tail (arrow indicates plausible direction of strain generated during the reaction). (E) Plot of the change in strain with the progress of the TAAC reaction (percent conversion) at 85 °C for LL (error bar shown in relative strain is obtained by the SD method).

Fig. 4.

(A) Comparison of crystal packing arrangement of LL and DD, viewed along the bc plane. (B) Chemical structures. (C) Time-dependent ¹H NMR spectra of DD crystals undergoing TAAC reaction at 80 °C. (D) PXRD comparison of DD before and after TAAC reaction. (E) MALDI-TOF spectrum of dipeptide DD heated at 80 °C for 7 d.

Fig. 5.

Optical microscopic images of a crystal of dipeptide DD (A) kept at rt for 1 mo; (B) after heating at 85 °C for 1 d, showing the left-handed twisted crystal; and (C and D) after heating longer crystal at 85 °C for more than 2 d, forming four and seven twists, respectively. Optical microscopic images of crystals of dipeptide LL and DD kept together (E) before heating and (F) after heating at 85 °C for 1 d. The arrows indicate the handedness of twist in each case. (Scale bars in C–F: 200 µm.)

Fig. 6.

Optical microscopic images of thinner crystal (A) before and (B) after heating at 85 °C for 1 d. Optical microscopic images of thicker crystal (C) before and after heating for (D) 1 d and (E) for 3 d. (F) Plot of energy versus angle of twist of various dipeptide crystals (DD and LL) having different dimensions. (Scale bar: 200 µm.)