Investigating the properties of l-lysine dendrimers through physico-chemical characterisation techniques and atomistic molecular dynamics simulations

Poly(l-lysine) (PLL) dendrimers up to generation 6, both as their ammonium trifluoroacetate salts and their boc-protected intermediates were characterised using multi-detector size exclusion chromatography (MD-SEC) and Taylor dispersion analysis (TDA) to accurately determine properties including molar mass, intrinsic viscosity (IV), refractive index and hydrodynamic size. Atomistic molecular dynamics (MD) simulations were used to gain structural insights into the experimental results and to provide further predictions on pH effect, solvent accessibility and radius of gyration. For both sets of dendrimers, increases in refractive index increment and intrinsic viscosity were observed across early generations that reduced by later generations. The boc-protected dendrimers were found to have flatter molecular density profiles across the different generations compared to the deprotected PLL dendrimers in their salt forms, which had more open structures thought to be driven by electrostatic repulsion. This is the first experimental report of this behaviour for PLL dendrimers, that were otherwise thought to have the same density across generations ascribed to be from their asymmetrical branch-cells that make up the structures. This work has demonstrated the power of combining advanced analytical characterisation techniques with MD simulations to provide detailed structural data for PLL dendrimers which hold much promise in drug delivery applications.