Is the Smallest Molecular Trefoil Knot Actually the Tightest One?

Tightness engineering has evolved as an efficient strategy for the design of knotted, woven, and entangled molecules and materials with desired properties and functions since tightness is a primary parameter that determines the property of a knotted strand. However, as an attractive topic that inspires mathematicians, physicists, chemists, and biologists, whether the smallest knot is exactly the tightest one remains unaddressed experimentally. To tackle this challenge, a series of organic trefoil knots with the backbone-atom as short as 70 have been successfully synthesized by developing a new modular self-assembly approach in this study. To our great surprise, with the help of gradient tandem mass spectrometry, the quantitative tightness evaluation suggested that the molecular trefoil knot with a backbone crossing ratio (BCR) of 24.0 is even tighter than the one with a BCR of 23.3 (i.e., the smallest organic trefoil knot with the shortest ropelength synthesized so far), thus demonstrating an unexpected yet interesting odd-even effect to enhance the understanding of the tightness regulation of molecular knots.