This is the final issue of ACS Combinatorial Science. I write these words with a profound sense of gratitude to the many authors and reviewers who have contributed to its pages, to our Editorial Advisory Board members who have provided wise counsel, and to the small but mighty group of associate editors and staff who have made the journal a joy to put together. I also write with both sadness and confidence at the literal and figurative turning of the page that the journal’s closing represents. Volume 1 of the Journal of Combinatorial Chemistry appeared on Jan. 12, 1999, under the direction of Founding Editor-in-Chief Anthony W. Czarnik. Tony was involved in the combi-chem revolution from its earliest days, when the idea of making and testing libraries of potential small-molecule drugs was new, and the nascent field was dominated by concerns about how parallel synthesis could be done and how compounds could be adequately characterized. New instruments for parallel reactions and purifications were all the rage, new ideas for molecular tagging or bead sorting were eagerly traded at meetings, and companies were founded and folded at a dizzying pace. But the heart of the Journal of Combinatorial Chemistry was always the chemistry: good reactions discovered and optimized for the synthesis of potentially useful molecular structures. The potential power of the field, at least to those moving into it, was obvious. For the most part, I shall not cite particular papers here, for fear of leaving out countless worthy contributions. But, for me, a 1996 review(1) by Wayne Guida and colleagues was critical to my appreciation of the subject. It posed the startling hypothesis that the potential size of the ultimate library of drug-like molecules was essentially infinite, estimated at up to 10⁶³ distinct structures. This suggested that there must be a very large number of chemical answers to every question in any field that relied on molecular structure and properties. How to find some of those answers became a motivating concern for a substantial number of investigators, and the field of combinatorial chemistry was born. I succeeded Dr. Czarnik as Editor-in-Chief in late 2010, understanding that the field of drug discovery had undergone a revolution with the rollout of the first monoclonal antibody blockbuster, Humira (adalimumab). Antibodies are made by combinatorial synthesis and screening, whether by the immune system or by the laboratory investigator using techniques such as phage display. In appreciation of this, and a parallel understanding that the properties of polymeric materials and other systems of interacting molecular components were being developed by new methods of synthesis and analysis, the ACS agreed to change the name of the journal to ACS Combinatorial Science. As we wrote then, “The name change signals an expansion of the journal’s scope to include combinatorial and evolutionary approaches to problems in biology, molecular biology, materials science, and catalysis development, in addition to the journal’s traditional focus on synthetic chemistry methods and high-throughput drug discovery.” And we were off on a very interesting ride. ACS Combinatorial Science was the first and only ACS journal to be devoted to a way of doing science, rather than to a specific field of knowledge or application. It was perhaps, therefore, destined to be transient, since methods change. It is now undeniable that combinatorial approaches are woven deeply into the fabric of modern therapeutic development. Few companies pursuing a new small-molecule drug would think twice about making a candidate library to probe structure–activity relationships in a scaffold family, and every biotech startup, or academic laboratory in chemical biology for that matter, has at its fingertips powerful tools for generating and testing biomolecular libraries of immense size. The fields that use solid-state and polymeric materials, from photoelectronics to hydrogels to nanotechnology, now have at their disposal well-accepted methods of making and testing candidates of varying composition. New analytical methods have always been a vital part of combinatorial exploration, and these are now widely distributed and ever improving. Thus, at least the initial development of combinatorial molecular science and technology may be considered complete. Its impact has been profound, and its methods will continue to shape our world and help answer society’s most critical challenges. New chemistry will always infuse library synthesis and materials development. Biomolecular evolution will continue to grow in power and sophistication. And new excitement in such areas as machine learning and DNA-encoded libraries will continue to appear. I will look for all of these in the pages of other journals that cover an enormous range of subjects. And I commend all of you readers of this journal to many happy interactions in the combinatorial enterprise that is research itself and to the insights and discoveries that emerge from them. Views expressed in this editorial are those of the author and not necessarily the views of the ACS. This article references 1 other publications.

中文翻译：

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ACS 组合科学：1999 年 1 月 - 2020 年 12 月

这是ACS Combinatorial Science的最后一期。我写下这些话，深深地感谢为它的页面做出贡献的许多作者和审稿人、提供明智建议的编辑顾问委员会成员，以及一小群强大的副主编和工作人员。杂志很高兴放在一起。我也以悲伤和自信的心情写下期刊结束时所代表的字面和比喻性的翻页。组合化学杂志第 1 卷在创始主编 Anthony W. Czarnik 的指导下，于 1999 年 1 月 12 日出现。托尼从一开始就参与了组合化学革命，当时制作和测试潜在小分子药物库的想法是新的，新兴领域主要关注如何进行平行合成以及化合物如何进行被充分表征。用于平行反应和纯化的新仪器风靡一时，分子标记或珠子分类的新想法在会议上热切地交易，公司以令人眼花缭乱的速度成立和倒闭。但《组合化学杂志》的核心始终是化学：发现并优化了用于合成潜在有用分子结构的良好反应。该领域的潜在力量，至少对于那些进入它的人来说，是显而易见的。大多数情况下，我不会在这里引用特定的论文，以免遗漏无数有价值的贡献。但是，对我而言，Wayne Guida 及其同事 1996 年的评论 (1) 对我对该主题的欣赏至关重要。它提出了一个惊人的假设，即最终的类药物分子库的潜在大小基本上是无限的，估计高达 10 ⁶³不同的结构。这表明在任何依赖于分子结构和性质的领域中，每个问题都必须有大量的化学答案。如何找到其中的一些答案成为了大量研究人员的一个令人兴奋的问题，于是组合化学领域诞生了。2010 年底，我接替 Czarnik 博士担任主编，我了解到随着首个单克隆抗体重磅炸弹 Humira（阿达木单抗）的推出，药物发现领域经历了一场革命。抗体是通过组合合成和筛选制造的，无论是由免疫系统还是由实验室研究人员使用噬菌体展示等技术。为鉴赏此，ACS 组合科学。正如我们当时所写的那样，“更名标志着该期刊的范围扩大了，除了该期刊传统上关注合成化学方法和高- 通量药物发现。” 我们开始了一段非常有趣的旅程。ACS组合学是第一个也是唯一化学学会杂志将专门一个方式做科学，而不是针对特定的知识或应用领域。因此，它也许注定是短暂的，因为方法会改变。现在不可否认的是，组合方法已深深融入现代治疗发展的结构中。很少有公司在开发新的小分子药物时会三思而后行，在构建候选库以探测支架家族中的结构-活性关系时，每家生物技术初创公司或化学生物学学术实验室都拥有触手可及的强大工具生成和测试巨大的生物分子库。使用固态和聚合物材料的领域，从光电子学到水凝胶再到纳米技术，现在可以使用广为接受的方法来制造和测试不同成分的候选物。新的分析方法一直是组合探索的重要组成部分，这些方法现在广泛分布并不断改进。因此，至少组合分子科学和技术的初步发展可以被认为是完整的。它的影响是深远的，它的方法将继续塑造我们的世界并帮助应对社会最关键的挑战。新化学将始终注入文库合成和材料开发。生物分子进化的力量和复杂性将继续增长。机器学习和 DNA 编码库等领域的新兴奋将继续出现。我将在涵盖广泛主题的其他期刊的页面中寻找所有这些内容。我赞扬本期刊的所有读者在研究本身的组合事业中进行了许多愉快的互动，以及从中产生的见解和发现。本社论中表达的观点是作者的观点，不一定是 ACS 的观点。本文引用了 1 篇其他出版物。