Conversely, the extended and water-soluble polymer PEG 35 kDa is presented alongside other EPO SCNPs that exhibited extendedness (EPO18, EPO59, EPO229, and EPO308). In terms of the copolymer design features provided in Table (monomer composition, DP, valence, molecular weight, and HLB), there is no clear distinction in the physicochemical characteristics between these two groups, although extended copolymers and copolymer conjugates tended to exhibit greater hydrophilicity with a higher weighted HLB. This is further evidence that the problem of SCNP design does not contain a simple solution with a single parameter. We can, however, visualize a clear gap between these two groups of samples in terms of measured Rg/Rh and Porod exponent as compact macromolecules tended towards Rg/Rh ~ 0.775 and Porod exponent from 3.0-4.0, while extended ones tended towards Rg/Rh > 1.00 and Porod exponent < 2.0. The gap suggests that incorporation of experimental data may be useful in defining a framework for SCNP structural design. Also, SEC-MALS was completed to quantify molecular weight and Đ for copolymer backbones (Table and Figure ) while UV-vis spectroscopy was conducted to determine DBCO incorporation which has implications for valency (Table ). Further, SAXS data are illustrated for the same compact and extended EPO-SCNPs from the random screen and ML-guided design alongside controls BSA and PEG 35 kDa (Figure ). This includes the SAXS intensity profiles, normalized Kratky plot, and Porod plot of the compact copolymer conjugates (ML EPO24, EPO119, EPO163, EPO166, and EPO172) and BSA (Figure ). The same was included for extended copolymer conjugates (EPO18, EPO59, EPO229, and EPO308) and PEG 35 kDa (Figure ). There was reasonable overlap in SAXS intensity profiles of the synthesized copolymers and copolymer conjugates with the controls. Further, characteristic behavior of macromolecular compactness and flexibility were exhibited through respective intensity, Kratky, and normalized plots (Figures ). Compact and extended SCNPs displayed SAXS features similar to highly ordered protein BSA and the extended polymer PEG, respectively. While the SAXS intensity profiles show agreement between synthesized SCNPs and their respective compact and extended controls, normalized Kratky plots qualitatively confirm that the degree of order is also in reasonable agreement. Interestingly, the ML EPO24 SCNP exhibits order more similar to that of BSA when compared against other SCNPs from the random screen (Figure ). These normalized Kratky plots can be useful in the case of combinatorial libraries that may contain various measured concentrations and thus differences in scattering intensity at zero angle, referred to as I(0). Therefore, deviations from BSA in terms of peak broadness and intensity in the normalized Kratky plot reflect on the varying degrees of order.