Department of Chemistry, University of Bergen , Allégaten 41, N-5007 Bergen, Norway.
Inorganic Computational Chemistry Group, Department of Chemistry, University of Warwick , Gibbet Hill Road, Coventry CV4 7AL, Great Britain.
J Chem Inf Model. 2015 Sep 28;55(9):1844-56. doi: 10.1021/acs.jcim.5b00424. Epub 2015 Sep 14.
We describe a method for the design of multicyclic compounds from three-dimensional (3D) molecular fragments. The 3D building blocks are assembled in a controlled fashion, and closable chains of such fragments are identified. Next, the ring-closing conformations of such formally closable chains are identified, and the 3D model of a cyclic or multicyclic molecule is built. Embedding this method in an evolutionary algorithm results in a de novo design tool capable of altering the number and nature of cycles in species such as transition metal compounds with multidentate ligands in terms of, for example, ligand denticity, type and length of bridges, identity of bridgehead terms, and substitution pattern. An application of the method to the design of multidentate nitrogen-based ligands for Fe(II) spin-crossover (SCO) compounds is presented. The best candidates display multidentate skeletons new to the field of Fe(II) SCO yet resembling ligands deployed in other fields of chemistry, demonstrating the capability of the approach to explore structural variation and to suggest unexpected and realistic molecules, including structures with cycles not found in the building blocks.
我们描述了一种从三维（3D）分子片段设计多环化合物的方法。这些 3D 构建块以受控的方式组装，并识别出可封闭的片段链。接下来，识别这些形式上可封闭链的闭环构象，并构建环状或多环分子的 3D 模型。将该方法嵌入进化算法中，得到一种从头设计工具，能够改变具有多齿配体的过渡金属化合物等物种中环的数量和性质，例如配体的齿合度、桥的类型和长度、桥头基团的同一性以及取代模式。该方法在设计用于 Fe(II) 自旋交叉（SCO）化合物的多齿氮基配体方面的应用被提出。最佳候选物显示出多齿骨架，这在 Fe(II) SCO 领域是新的，但类似于化学其他领域中使用的配体，证明了该方法具有探索结构变化并提出意想不到的现实分子的能力，包括在构建块中未发现的环的结构。
