Title: Rapid Evaluation of Synthetic and Molecular Complexity for In Silico Chemistry Authors: Tharun Kumar Alluâ and Tudor I. Oprea Department of Computer Science and Division of Biocomputing University of New Mexico School of Medicine Rapid methods to evaluate molecular complexity and synthetic feasibility are becoming increasingly important for in silico chemistry. We propose a new metric that evaluates both synthetic and molecular complexity (SMCM) starting from chemical structures. Against molecular weight, SMCM has the lowest fraction of adjusted variance (R2 = 0.553) on a series of 261,048 diverse compounds, when compared to the complexity metric of Baron and Chanon (R2=0.777; J. Chem. Inf. Comput. Sci. 2001, 41, 269-272) and RĂĽcker (R2=0.895 for log10 complexity values; J. Chem. Inf. Comput. Sci. 2004, 44, 378-386), respectively. SMCM counts atom types, substructure patterns and atomic and bond parameters from Balaban (J. Chem. Inf. Comput. Sci. 1998, 38, 395-401) and can be further tailored to rapidly evaluate virtual (combinatorial) libraries.