Nolte was considered to be one of the pioneers of the field of supramolecular chemistry, which encompasses the design and synthesis of new chemical structures from low molecular weight compounds and biopolymers using non-covalent interactions.

He published many studies on supramolecular assembly and biomimetic catalysts, which find applications in the field of nanomaterials and medicine.

[6] He continued his studies at the same university, earning a Ph.D. in physical organic chemistry on the synthesis and properties of a new type of polymer in 1973 (supervisor Wiendelt Drenth).

[7] After a postdoctoral stage with Nobel laureate Donald J. Cram at UCLA, he joined the Faculty of Science of Utrecht University as an assistant professor.

[11] Later studies on atropisomeric polymers derived from isocyanopeptides revealed that these compounds formed superhelical structures by a supramolecular process of hierarchical self-assembly.

[12][13] Other polyisocyanide derivatives formed hydrogels at very low concentrations, displaying strain stiffening, i.e. they become stronger when a force is applied, a property that previously had only been found in natural materials.

[24][25][26] He also designed molecular machines that can encode digital information into single polymer chains in the form of chiral chemical groups.

[38] After his retirement, he twice received a prestigious ERC Advanced Grant to study the encoding of information into polymers by supramolecular catalytic machines.