Complex coacervation describes the phase separation of at least two charged components, usually involving a polyionic species. We reasoned that combining our in-situ generated cationic building blocks with polyanions enables us to create droplets through complex coacervation. Given the chemically fueled nature of our chemically fueled dynamic combinatorial library, complex coacervation of the library members should lead to active droplets, i.e., those requiring fuel to be sustained. We first tested the peptide structure Ac-FRGMYRGD-OH in combination with the polyanion PSS because it forms large amounts of linear dimer and cyclodimer products in response to EDC (Fig. ). Besides, the peptide is zwitterionic (+2, -2) and overall charge neutral. In contrast, the linear dimer has an overall charge of +1, and the cyclodimer has an overall charge of +2. In other words, we expect minimal interaction between the peptide and polyanions. In contrast, the products of the reaction cycle are expected to interact strongly with the polyanion to form complex coacervatebased droplets. This chemically fueled charge switching has been previously explored in active droplets but not in the context of a dynamic combinatorial library. To further enhance the interaction with polyanions, we added methionine (M), known for its ability to interact with p-systems, thereby driving phase separation. Indeed, when we combined 10 mM of the peptide with 20 mM of EDC in 200 mM MES buffer at pH 5.3 in the presence of 1 mM of the polyanion PSS, turbidity quickly emerged. The turbidity peaked at around 1 hour after fuel addition and slowly declined over 24 hours when the absorbance value reached its initial value again (Fig 3A). We tested the coacervate composition by spinning down the droplets and analyzing the supernatant. After 90 minutes, the EDC was fully consumed, and we found that 31% of the total cyclodimer was taken up into the droplets together with 15 % of the linear dimer. After 450 minutes, no more peptide precursor is present in the coacervate droplets, and 20% of the linear dimer and 38% of the total cyclodimer concentration in the mixture are concentrated in the coacervate droplets. These results show nicely that the cyclodimer is the most potent coacervating agent among library members. Similar mixtures without PSS did not show any evidence of assemblies, from which we conclude that the assemblies are a complex coacervate between peptide and PSS. We further studied the assemblies by confocal microscopy and found micron-sized droplets that rapidly fused, from which we concluded they were liquid (Fig. ). Furthermore, FRAP experiments revealed fast fluorescence recovery with a diffusion coefficient (D) of 0.0145 µm 2 /s. To test whether the PSS-based coacervates were able to take up functional oligonucleotides, we combined them with the RNA-oligonucleotides Cy5-U15 or Cy5-A15, or the DNA-oligomer Cy3-(AGTC)10. In all cases, the oligonucleotides were taken up into the coacervates but were more concentrated on the periphery of the droplets, suggesting a demixing tendency of the two polyanions. Aside from that, the coacervates were significantly smaller compared to those made from pure PSS. To test the peptide's versatility in making coacervates, we tested it with other anionic (block co-) polymers. First, we analyzed it in combination with 1 mM polyU as polyanion. The sample transiently turned turbid with EDC, similar to using PSS as polyanion (Supporting Figure ). These polyU-based coacervates appeared as spherical droplets slightly smaller than the corresponding PSS-based coacervates (Fig. ). Next, we combined the peptide with block copolymers made from PEG and PSS to further tune their properties, i.e., change their size. To test its ability to form complex coacervate core micelles (C3Ms), we applied 20 mM EDC to 10 mM of peptide in the presence of 1 mM of PEG5K-b-PSS77 and monitored the assembly process by DLS (Fig. ). This analysis showed a quick increase in scattering rate after EDC was added, indicating the immediate complexation of block copolymer by the dynamic combinatorial library members. The maximum scattering rate was reached after 1 hour, coinciding with the maximum turbidity for the complex coacervation of PSS homopolymer. CryoTEM further corroborated the formation of block copolymer assemblies upon fueling (Fig. ). Specifically, the micrographs show large compound micelles of 80 to 100 nm diameter that coexist with polymersomes with a diameter around 150 nm. These sizes matched well with the z-average size obtained from DLS (Supporting Figure ). The lifetime of the assemblies could be increased by adding more peptides and EDC.