Exploration of the Nucleation Pathway for Supramolecular Fibers

• Published in: Journal of chemical information and modeling 2023-04, Vol.63 (8), p.2419-2426
• Main Authors: Tang, Phu K., Khatua, Prabir, Carnevale, Vincenzo, Loverde, Sharon M.
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - chemistry; Aqueous solutions; Aromatic compounds; Computational Chemistry; Droplets; Molecular dynamics; Nucleation; Polyethylene glycol; Polyethylene Glycols; Self-assembly; Stacking
• ISSN: 1549-9596; 1549-960X
• DOI: 10.1021/acs.jcim.3c00049

The pathway for supramolecular fiber formation is coupled with the underlying order of the self-assembling molecules. Here, we report on atomistic molecular dynamics simulations to characterize the initial stages of the self-assembly of a model drug amphiphile in an aqueous solution. We perform two-dimensional metadynamics calculations to characterize the assembly space of this model drug amphiphileTubustecan, TT1. TT1 is composed of the hydrophobic anticancer drug, Camptothecin (CPT), conjugated to a hydrophilic polyethylene glycol (PEG) chain. We find that the aromatic stacking of CPT drives the formation of a higher-density liquid droplet. This droplet elongates and can form a higher-ordered supramolecular assembly upon reorganizing and forming an interface and additional aromatic stacking of the drugs. We show that novel reaction coordinates tailored to this class of molecules are essential in capturing the underlying degree of molecular order upon assembly. This approach can be refined and extended to characterize the supramolecular assembly pathway of other molecules containing aromatic compounds.