The first attempts to synthesize mono-functionalized mixHC [8] in solution according to the protocol developed for cycHC [8] 18 were promising. The condensation of biotin and CU taken in stoichiomeric 1:7 molar ratio with paraformaldehyde, mediated by trifluoroacetic acid in acetonitrile, produced mixHC [8] and cycHC [8] in 10% and 38% yields, respectively (see SI S4). The ratio of the macrocycles did not reflect the statistical distribution based on the starting monomer ratio, which implied a strong influence of the chemical parameters. We envisioned that mixHC [8] may be assembled with higher efficiency in the solid state, where templation is enhanced due to a high concentration of reactants and the desolvation effect. According to the previous study, self-assembly in the solid state required just a minute amount of a liquid additive to facilitate proton transfer and delivery of the anionic template, as well as to promote conformational flexibility. The complexity of a dynamic covalent library (DCL) drastically increases in multi-component reactions, for instance, incorporation of non-C 2 symmetric (R,S)cyclohexa-1,2-diylurea units resulted in higher stereochemical diversity and the formation of several diastereomeric HCs (i.e, cis-cycHC [6] and inverted-cis-cycHC [6]). Similarly, self-assembly of chiral CU and non-C 2 symmetric biotin into linear and cyclic oligomers can be realized via various combinations, considering the possibilty of different orientations of the biotin unit (see SI S3). For instance, all forms with the length from 2 to 10 result in ca. 50,000 cyclic and linear oligomers. However, the number of possible products can be decreased by templation. Variation of position, orientation and number of B and CU monomers leads to 498 potential 8-membered macrocycles (Figure , see SI S5). Full conversion of the 1:7 ratio of B and CU into HC [8]s is expected to direct 498 combinations to 12% and 82% of mixHC [8] and cycHC [8], respectively (Figure , and SI Table ). [8] and chimeric mixHC [8]s shown in this work. Complexity of intermediates in the dynamic covalent library is expressed via possible number of combinations of oligomers, HC [8]s and the abundance of major HC [8]s from the 1:7 (B:CU) ratio of starting materials. Best reaction conditions, affording 37% and 38% yields of mixHC [8] and cycHC [8], respectively: 1 eq. B, 7 eq. CU, 8 eq. (CH2O)n in presence of 2 eq. HPF6. and 1 eq. KPF6, milled at 30 Hz for 60 min and aged at 60°C for 24h.