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In the past 20 years, patients with rheumatoid arthritis (RA), Crohn's disease (CD), and other immune diseases have witnessed the impact of a great treatment advance with the availability of biological TNFα inhibitors. With 5 approved anti-TNFα biologics on the market and soon available biosimilars, patients have more treatment options and have benefited from understanding the biology of TNFα. Nevertheless, many unmet needs remain for people living with TNFα-related diseases, namely some side effects and tolerance of current anti-TNFα biologics and resistance to therapies. Furthermore, common diseases such as osteoarthritis and back/neck pain may respond to anti-TNFα therapies at early onset of symptoms. Development of new TNFα inhibitors focusing on TNFR1 specific inhibitors, preferably small molecules that can be delivered orally, is much needed.

Monodisperse molecular nanotubes, particularly those with uniform lengths, are challenging targets for chemical synthesis. Here we report the general design and efficient synthesis of finite molecular nanotubes, utilizing a dynamic assembly strategy to precisely pile axially functionalized macrocycles by chemical connections. Discrete tubular molecules, ranging from 7.8 k to 19.8 k Dalton with covalent or coordinative connections, have been prepared from modular macrocyclic building blocks through highly convergent routes.The discrete molecular nature and structural anisotropy of these synthetic tubes warrant post-synthesis modifications and solution processing methods, as demonstrated by the controllable orientations when deposited onto different prefabricated surfaces.