First, the performance of uniqueness and novelty for all models is close to 100% (except that the uniqueness ratio of molecules generated by EDM on AOMAD database is 88.56%). Therefore, the rows of uniqueness, novelty, and V&U&N are omitted in Table . Nevertheless, the task of learning the distribution of fused-rings and the fragment connection modalities of molecules in FORMED and AOMAD poses a great challenge to the baseline models. The molecules generated by these methods almost all have a large number of ring breakages, overlaps, and other situations that violate the basic chemical rules as shown in Supplementary Figure , resulting in a low validity. As shown in Table , the validity of the baseline models ranges from 70% to 88% (FORMED datasets), and with the increase of molecular weight and the number of rings on AOMAD datasets, the validity of all baseline models significantly drops to 49%-79%. In contrast, O 2 -GEN still maintains the validity of nearly 97% on both datasets.