Structural complexity is a property that has been associated with the drug-likeness of compound data sets. Comparisons of the structural complexity of approved drugs and compounds under pre and clinical development have suggested that compounds in clinical use have, in general, an increased fraction of sp carbons that has been taken as a rough measure of structural complexity. Also, complexity has been considered as an indicator of selectivity or deceased promiscuity regarding biological interactions between small-molecule libraries. Yet, structural complexity, although intuitive in principle, can be quantified in different ways systematically and consistently and today is an area of research, both computationally and experimentally. One of the simplest but consistent ways to quantify complexity that has been adopted in cross-comparisons is the fraction of sp 3 carbons. Considering this metric as an approximate but well-established metric to quantify the structural complexity of compound data sets, we concluded that compounds in NPDBEjeCol were the most complex of all natural product data sets (median value of 0.63)including natural products from COCONUT a reported value of 0.51. and more complex than the set of approved drugs (Table ). The second most complex natural product database was PeruNPDB, and all four natural products data sets had an overall larger median value of fraction of sp 3 carbons than approved drugs, as previously noted for other natural product collections. Similarly, compounds in NPDBEjeCol had the largest median values of bridgehead atoms (0.41) of all databases. In natural products, this is relevant because the increased structural complexity has been associated with the overall increased target selectivity or less promiscuity as compared to synthetic organic compounds with a smaller proportion of sp 3 carbons. Similar to the values obtained for the entire chemical structures, the fragment libraries obtained from NPDBEjeCol and NuBBEDB had the largest fraction of sp 3 carbons (median values of 0.63) (Table ), followed by fragment libraries from PeruNPDB and BIOFACQUIM, and finally from approved drugs. Notably, in general, the complexity of fragment libraries from NPDBEjeCol and NuBBEDB was higher than the complexity of fragments generated from COCONUT, which had a reported value of 0.56. 6