Sequence Programmable Triazine-Thymine Synthetic Ligands

在化学系大分子、超分子和纳米化学项目的支持下，康奈尔大学的克里斯托弗·阿拉比将设计一种化学平台，该平台可以用多条“粘性”侧链进行编程，创造出类似于双链DNA的互补链对，能够在没有水的情况下组装。一个物理类比是一条带有黑色和白色珠子的串珠项链，它们可以彼此结合，但不能结合自己(即，黑色绑定白色，但不能绑定黑色)。因此，一条既有黑色珠子又有白色珠子的项链粘在另一条珠子上的能力将取决于项链中每种珠子的数量、项链的长度以及黑白珠子在每条项链中的位置。这项工作的目的是在分子水平上设计这样一种系统，其中粘性的黑色和白色珠子分别是被称为二氨基三嗪和胸腺嘧啶的分子。掌握这些可以在非水环境中进行特定配对的粘性链的设计，有可能在设计和组装新的功能材料方面开辟新的和令人兴奋的机会。教育和外联活动将通过一个共同的主题纳入整个研究项目，该主题侧重于促进对等学习，并增强有抱负的年轻科学家在向更广泛的公众传播STEM(科学、技术、工程和数学)思想方面的领导地位。总体而言，拟议中的项目预计将创造新的知识，即沿着聚合物链的“粘性”构建块的组成和排序如何影响它们形成可用于功能材料组装的选择性分子“维克罗尔”的能力。这项提议的中心目标是设计一种具有分子识别基序的可编程低聚物平台，可用于在非水介质中对杂交信息进行编码。为了设计合成的可编程配体，可扩展的序列定义寡氨基甲酸酯(SeDOC)平台将被利用二氨基三嗪和胸腺嘧啶悬垂结合基序来决定序列、溶解性和杂交强度。拟议的可编程SeDOC配体将被设计为可溶于有机溶剂，而不需要任何额外的试剂。与DNA(2‘-脱氧核糖核酸)类似，相互作用的悬挂基序的数量和SeDOC主干的长度将定义编码空间(即序列)。然而，与DNA不同的是，强杂交只需要几个结合基序(实验表明，在高Ka=高平衡结合常数下)，这是因为在无质子有机溶剂中没有排斥性的阴离子骨架，并且二氨基三嗪-胸腺嘧啶相互作用具有很强的结合亲和力。该提案将调查侧基组成和序列对杂交强度的影响，以设计可在各种材料科学应用中用作配体的选择性互补SeDOC链对。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

With the support of the Macromolecular, Supramolecular and Nanochemistry Program in the Division of Chemistry, Christopher Alabi of Cornell University will design a chemical platform that can be programmed with multiple "sticky" side chains to create complementary pairs of chains similar to double-stranded DNA, that are able to assemble in the absence of water. A physical analogy is a beaded necklace with black and white beads that can bind to each other but not to themselves (i.e., black binds white but not black). Thus, the ability of a necklace with both black and white beads to stick to another beaded necklace will depend on the number of each type of beads in the necklace, the length of the necklace, and the positions of the black and white beads in each necklace. This work aims to design such a system on a molecular scale where the "sticky" black and white beads are molecules referred to as diaminotriazine and thymine, respectively. Mastering the design of these "sticky" chains that can undergo specific pairing in non-aqueous environment has the potential to open up new and exciting opportunities in the design and assembly of new functional materials. Educational and outreach activities will be integrated throughout this research project through a common theme that is focused on promoting peer-to-peer learning and empowering young aspiring scientists to take up leadership positions in communicating STEM (science, technology, engineering and mathematics) ideas to the broader public. Overall, the proposed project is expected to create new knowledge on how the composition and ordering of "sticky" building blocks along a polymer chain affects their ability to form selective molecular "velcros" that can be used in functional materials assembly. The central goal of this proposal is to design a programmable oligomer platform with molecular recognition motifs that can be used to encode information for hybridization in non-aqueous media. To design synthetic programmable ligands, the scalable sequence-defined oligocarbamate (SeDOC) platform will be exploited with diaminotriazine and thymine pendant binding motifs that dictate sequence, solubility, and hybridization strength. The proposed programmable SeDOC ligands will be designed to be soluble in organic solvents without the need for any additional reagents. Similar to DNA (2'-deoxyribonucleic acid), the number of interacting pendant motifs and length of the SeDOC backbone will define the coding space (i.e., sequence). However, unlike DNA, only a few binding motifs will be required for strong hybridization (as seen experimentally in a high Ka = high equilibrium association constant) due to the absence of a repulsive anionic backbone and the strong binding affinity of the diaminotriazine-thymine interaction in aprotic organic solvents. The proposal will investigate the effect of pendant group composition and sequence on hybridization strength toward the design of selective pairs of complementary SeDOC strands that can be used as ligands in various materials science applications.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.