How Subtle Changes Can Make a Difference: Reproducibility in Complex Supramolecular Systems

Abstract

The desire to construct complex molecular systems is driven by the need for technological (r)evolution and our intrinsic curiosity to comprehend the origin of life. Supramolecular chemists tackle this challenge by combining covalent and noncovalent reactions leading to multicomponent systems with emerging complexity. However, this synthetic strategy often coincides with difficult preparation protocols and a narrow window of suitable conditions. Here, we report on unsuspected observations of our group that highlight the impact of subtle "irregularities" on supramolecular systems. Based on the effects of pathway complexity, minute amounts of water in organic solvents or small impurities in the supramolecular building block, we discuss potential pitfalls in the study of complex systems. This article is intended to draw attention to often overlooked details and to initiate an open discussion on the importance of reporting experimental details to increase reproducibility in supramolecular chemistry.

Keywords: Complexity; Reproducibility; Solvent Effects; Supramolecular Systems.

Figure 1

Molecular structures of Glc₃‐BTA and Glc₂‐BTA; cryo‐TEM of Glc₃‐BTA/Glc₂‐BTA mixtures (left) and pure Glc₃‐BTA (right). Details on the analytical methods are given in the Supporting Information.

Scheme 1

Formation of the Michael addition product between (E)‐nitrostyrene and 2,4‐pentadione after 2 h in CDCl₃ catalyzed by NaPy purified by recrystallization (I, 20 mM) or column chromatography (II; 20 mM), K₂CO₃(III; 5 mM, hardly active) or NaPy (20 mM)/K₂CO₃ (5 mM) (IV). Data taken from ref. [30, 31, 32].

Figure 2

Helix inversion of (S)‐BPT and the related CD trace at 258 nm upon removal of ppm amounts of water by drying via the nitrogen stream in the CD spectrometer. Data taken from ref. .

Scheme 2

CD spectroscopic kinetic investigation of the in situ synthesis of (S)‐BTA‐based supramolecular polymer from trimesoic acid chloride and tetrahydrocitronellyl amine with triethylamine base in the presence of different amounts of water in MCH (solvent). Color coding of the CD spectroscopic kinetic traces: orange—38 ppm water, red—28 ppm water, orange—18 ppm water. Data taken from ref. .

Figure 3

CD spectra of an aging n‐TTA sample in (R)‐CldMeOct after 14 h storage under inert and ambient conditions and after manual addition of water. The inset shows the decrease in CD intensity monitored at 266 nm over time (closed cuvette under air). Details on the analytical methods are given in the Supporting Information.

Scheme 3

Pathway complexity of the (S)‐OPV dimer, which undergoes kinetically or thermodynamically favored formation of the P‐ or M‐helical supramolecular polymer. The CD spectra of (S)‐OPV show the M‐ (blue line) and P‐helical aggregates (red line), and the molecular dissolved state (black line). Data taken from ref. .