Multiple competing pathways for chemical reaction: drastic reaction shortcut for the self-catalytic double-helix formation of helicene oligomers

A drastic reaction shortcut: thermal history determines the selection of competing pathways and reaction time for self-catalytic hetero-double-helix formation.


Materials
(P)-1 and (M)-2 were synthesized as described in our previous work. S1

< Freezing-defrosting/rapid experiment >
A solution of 1:1 (P)-1/(M)-2 mixture (total 5.0 × 10 −4 M, fluorobenzene) was heated at 70 °C for 30 min, snap cooled at −35 °C by immersing in a cooled bath at -35 °C, transferred to a CD cell adjusted to −25 °C, and allowed to settle for 15 min. The solution was rapidly heated at 25 °C, and allowed to settle for CD analysis (Fig. 3).
< Freezing-defrosting/constant-rate experiment (heating from -25 to 25 °C) at the rate of 2 Kmin −1 > A solution of 1:1 (P)-1/(M)-2 mixture (total 5.0 × 10 −4 M, fluorobenzene) was heated at 70 °C for 30 min, snap cooled at −35 °C by immersing in a cooled bath at -35 °C, transferred to a CD cell adjusted to -25 °C, and allowed to settle for 15 min. The solution was heated from -25 °C to 25 °C at the rate of 2 Kmin −1 , and allowed to settle for 120 min for CD analysis (Fig. S1).
< Simple-cooling/constant-rate experiment (cooling from 70 to 25 °C) at the rate of 2 Kmin −1 > A solution of 1:1 (P)-1/(M)-2 mixture (total 5.0 × 10 −4 M, fluorobenzene) was heated at 70 °C for 30 min. The solution was cooled from 70 °C to 25 °C at the rate of 2 Kmin −1 , and allowed to settle for 25 min for CD analysis (Fig. S2).  4. The molecular structures at the initial stage at 25 °C << CD Studies >> < Freezing-defrosting/rapid experiment > A solution of 1:1 (P)-1/(M)-2 mixture (total 5.0 × 10 −4 M, fluorobenzene) was heated at 70 °C for 30 min, snap cooled at −35 °C by immersing in a cooled bath at -35 °C, transferred to a CD cell adjusted to -25 °C, and allowed to settle for 15 min. The solution was rapidly heated at 25 °C and allowed to settle for 20 min, during which CD spectra were obtained at 20 sec intervals until 5 min and at 5 min intervals between 5 and 20 min (Fig. S3).

Fig. S3
(a) CD spectra of 1:1 (P)-1/(M)-2 mixture (total 5.0 × 10 −4 M, fluorobenzene) showing the initial state in the structural changes from random coil A at −25 °C to hetero-double helix C at 25 °C under the freezing-defrosting/rapid conditions. CD spectrum of S-random-coil A was obtained in our previous work. S2 (b) Extraction and magnification of (a).
< Simple-cooling/rapid experiment > A solution of 1:1 (P)-1/(M)-2 mixture (total 5.0 × 10 −4 M, fluorobenzene) was heated at 70 °C for 30 min providing an S-random-coil solution. The solution was rapidly cooled at 25 °C then allowed to settle for 5 min, during which CD spectra were obtained at 20 sec intervals (Fig. S4). showing the initial state in the structural changes from random coil A at 70 °C to hetero-double helix B at 25 °C under the simple-cooling/rapid conditions. CD spectrum of S-random-coil A was obtained in our previous work. S2 (b) Extraction and magnification of (a).
The spectra in Fig. S3 and S4 were very similar during the initial 300 seconds.

< Freezing-defrosting/rapid experiments >
A solution of 1:1 (P)-1/(M)-2 mixture (total 5.0 × 10 −4 M, fluorobenzene) was heated at 70 °C for 30 min, snap cooled at −35 °C by immersing in a cooled bath at -35 °C, transferred to a CD cell adjusted to -25 °C, and allowed to settle for 15 min. The solution was rapidly heated at 25 °C, allowed to settle for 2 min, and analyzed by NMR.

<Simple-cooling/rapid experiment >
A solution of 1:1 (P)-1/(M)-2 mixture (total 5.0 × 10 −4 M, fluorobenzene) was first heated at 70 °C for 30 min, rapidly cooled at 25 °C, allowed to settle for 2 min, and analyzed by NMR (Fig. S5). to -25 °C, and allowed to settle for 15 min. The solution was rapidly heated at 25 °C then allowed to settle for 2 min for DLS analysis.

A-to-C and A-to-B-to-C reaction after cooling at -10 °C < A-to-C reaction: Freezing-defrosting/rapid experiment with snap-cooling at -10 °C >
A solution of 1:1 (P)-1/(M)-2 mixture (total 5.0 × 10 −4 M, fluorobenzene) was first heated at 70 °C for 30 min, snap cooled to -35 °C for 15 min by immersing in a cooled bath at -35 °C, transferred to a CD cell adjusted to -10 °C, and allowed to settle for 30 min. Then, the solution was rapidly heated at 25 °C, and allowed to settle for 300 min (Fig. 5, green circles; Fig. S7a).
< A-to-B-to-C reaction: Trapping B by constant-rate cooling to -10 °C at the rate of 2 Kmin −1 then rapid-heating experiment > A solution of 1:1 (P)-1/(M)-2 mixture (total 5.0 × 10 −4 M, fluorobenzene) was first heated at 70 °C for 30 min, cooled from 70 C to −10 C at the rate of 2 K/min, and allowed to settle for 30 min at −10 C.
Then, the solution was rapidly heated at 25 °C, and allowed to settle for 5040 min (

S9
< Freezing-defrosting/rapid experiments > A solution of 1:1 (P)-1/(M)-2 mixture (total 2.5 × 10 −4 M, fluorobenzene) was heated at 70 °C for 30 min, snap cooled at −35 °C by immersing in a cooled bath at -35 °C, transferred to a CD cell adjusted to -25 °C, and allowed to settle for 15 min. The solution was rapidly heated either at 5 °C, 25 °C, or 40 °C, and allowed to settle for 50-780 min for CD analysis (Fig. S9).    The lines are drawn between points. S11 7. Temperature effect in the A-to-C reaction and A-to-B-to-C reaction < Freezing-defrosting/rapid experiment: A-to-C reaction > A solution of 1:1 (P)-1/(M)-2 mixture (total 5.0 × 10 −4 M, fluorobenzene) was heated at 70 °C for 30 min, snap cooled at −35 °C by immersing in a cooled bath at -35 °C, transferred to a CD cell adjusted to -25 °C, and allowed to settle for 15 min. The solution was rapidly heated either at 5 °C, 25 °C, 40 °C, or 50 °C and allowed to settle for 40-300 min for CD analysis (Fig. S13).

Fig. S13
The Δε (315 nm)/time profiles of 1:1 (P)-1/(M)-2 mixtures in fluorobenzene (total 5.0 × 10 −4 M) under freezing-defrosting conditions at different temperatures. The profiles at 5, 25, 40, and 50 °C are shown by blue, green, red circles, respectively. The lines are drawn between points. The inset shows the magnification of the profiles between 0 and 60 min. The Δε values at equilibrium at 5, 25, 40, and 50 °C are shown in purple, pale green, and brown lines, respectively, which were obtained in our previous work. S2
Slightly sigmoidal Δε/time profiles were obtained. min providing a solution of hetero-double helix C (Fig. S16). Another solution of (P)-1/(M)-2 mixture (total 5.0 × 10 −4 M, fluorobenzene, 0.60 mL) was heated at 70 °C for 20 min providing a solution of Srandom-coil A. The solution of S-random-coil A was cooled at 40 °C for 5 sec, and then was added to the solution of hetero-double helix C in the quartz cell in a ratio of 1:1 (hetero-double helix C:random coil A = 0.60 mL:0.60 mL), and the solution was allowed to settle for 240 min for CD analysis (Fig. S17).
Experiments in the mixing ratio of 1:2 (hetero-double helix C:random coil A = 0.40 mL:0.80 mL) and 1:3 (hetero-double helix C:random coil A = 0.30 mL:0.90 mL) were also conducted (Fig. S17).   S19b) for 40 min. Compare Fig. S17b with S18a, and also S17c with S18b: No decrease of Δε as shown by the red arrows appeared in this control experiments.

Addition of solvent (fluorobenzene) at 25 °C:
A solution of 1:1 (P)-1/(M)-2 mixture (total 5.0 × 10 −4 M, fluorobenzene, 0.60 mL) was transferred to a round quartz cell, heated at 70 °C for 20 min, and cooled at 25 °C for 20 min providing a solution of hetero-double helix B. Fluorobenzene was added to the hetero-double helix B solution in the quartz cell in a ratio of 1:1 (hetero-double helix B:fluorobenzene = 0.60 mL:0.60 mL), and the solution was allowed to settle for 20 min for CD analysis (Fig. S19d). Compare with Fig. S18c.

Addition of hetero-double helix B to hetero-double helix B at 25 °C:
A