Overall, the reproducibility between the two replicate screens was in broad agreement -23/24 (96%) resulted in the same automated reactivity analysis by HRMS. Taking into account minor changes in conversion ranging from <1% to <5%, 20/24 reactions gave reproducible 1 H NMR spectra. Of all the reactions, 75% of precursor combinations containing triamine A resulted in the formation of the MNLN or M2X3 targeted topologies as the major mass ion peak, whereas none of the combinations with triamine B resulted in the targeted species being identified in the HRMS spectra, suggesting a larger linker core is required to form a stable self-assembled species. Of the triamine B combinations, a higher proportion of ligand and intermediates were identified in the HRMS spectra (Supporting Information S2.3), indicating that while self-assembly with the metal ion was not successful, the imine condensations between B and the aldehydes had occurred. This conclusion was further confirmed by the observation that 92% of the reactions with triamine B showed high conversion based on the automated 1 H NMR analysis. This observation highlights the need for multiple characterization methods to be used in parallel for interpretation and determination of the outcome from automated highthroughput screens. Finally, of the precursor combinations containing triamine A, a clear effect on the assembly outcome can be observed on incorporating a methyl group and on varying its positional isomerism (ortho, meta, or para to the pyridyl nitrogen): when the methyl substituent is introduced in the para-position (4), far away from where metal coordination occurs, the assembly outcome is similar to the base pyridyl-aldehyde (1), but the likelihood of successfully forming the targeted MNLN or M2X3 species reduces as the methyl group is moved around the ring from the para-to meta-(3) to ortho-positions (2). We attributed this observation to increased steric hinderance around the metal center on co-ordination, which reduces the likelihood of MOC formation.