SusChEM: Mechanisms of small molecule activation in constrained molecular environments

在资源匮乏的现代，开发化学工艺，使其最终能够从现成的、廉价的、可再生的起始材料中产生有用的材料和燃料，是至关重要的。小分子（如氧或其近亲过氧化氢）是合成应用中氧原子的理想来源。在化学合成和能源生产中利用氧气的新策略可能导致环境清洁的氧化，产生水作为唯一的副产物，并依赖于现成的试剂。塔夫茨大学的Rybak-Akimova博士进行研究，以详细了解氧和过氧化物结合的途径以及化学系统中选定的反应性。她的目标是确定这些反应的“瓶颈”，并获得重要的基础知识，为在合成应用中设计高效无毒的试剂提供重要信息。该研究项目为研究生和本科生提供了高水平机械研究的培训机会，同时也参与了设计、制备、表征和应用小分子激活的新合成系统的合作努力。Rybak-Akimova博士计划通过塔夫茨STEM多样性中心积极招募女性和少数族裔学生参与该项目。对该地区公立学校的高中生的推广活动包括参观科学博览会并发表演讲，由梅德福和萨默维尔的高中生团体到塔夫茨大学的研究实验室进行实地考察，以及招募高中生作为暑期研究员。美国国家科学基金会化学部的大分子、超分子和纳米化学计划以及化学催化计划共同支持Rybak-Akimova博士的研究小组研究次级球体效应的作用，包括与空间大体积取代基和氢键的疏水相互作用，在选定的化学体系中。更具体地说，该项目研究：(1)O2在具有多电子氧化能力的空间保护金属中心的结合和活化(例如Pd(0)/Pd（II）或V(III)/V(V))，以及热不稳定的端对双氧加合物（金属-超氧中间体）与类似的稳定侧对金属-过氧物质的反应性；(2)过氧化物客体在羧酰胺隐体内的包封以及该过氧化物与外部添加的氧化剂或还原剂的反应性；(3)含酰胺的三维笼和类似的“开放”三足或二维大环宿主中金属结合氧中间体的生成和反应性；(4)高价过氧阴离子（如过氧钒酸盐）的阴离子识别与含酰胺的三脚，大环和选择性底物氧化笼。本研究旨在建立由控制空间体积水平和/或外围供质子基团数量和位置的配体支持的双氧与低价金属中心的逐步配位机制，在直接双混合动力学实验中测量这些物种与外部添加的底物的反应活性，鉴定活性氧化剂。在与外部氧化剂或还原剂的反应中，研究包裹在无金属宿主体内的过氧化物反应活性的立体和氢键调制，并确定电子转移和原子转移的机制。Tufts开发的堵流仪器和技术要求苛刻的快速反应动力学测量专业知识继续对机械研究的基础设施产生重大影响。

In the modern era of scarce resources, developing chemical processes that can eventually generate useful materials and fuels from readily available, cheap, renewable starting materials is of paramount importance. Small molecules (such as oxygen or its close relative, hydrogen peroxide) are ideal sources of oxygen atoms in synthetic applications. New strategies for utilizing oxygen in chemical synthesis and energy production may lead to environmentally clean oxidations that generate water as the only byproduct and rely on readily available reagents. Dr. Rybak-Akimova at Tufts University conducts research to gain a detailed understanding of the pathways in oxygen and peroxide binding and reactivity in selected examples of chemical systems. She aims to identify the "bottlenecks" of these reactions and gain fundamental knowledge important for informing the design of efficient and non-toxic reagents in synthetic applications. This research project provides opportunities for graduate and undergraduate students to be trained in high-level mechanistic studies while also participating in collaborative efforts to design, prepare, characterize, and apply new synthetic systems for small molecule activation. Dr. Rybak-Akimova plans to actively recruit female and minority students for the project through the Tufts Center for STEM Diversity. Outreach to high-school students from public schools in the area includes visits to and presentations at science fairs, field trips by groups of Medford and Somerville high school students to research laboratories at Tufts, and recruitment of high school students as summer researchers. The Macromolecular, Supramolecular and Nanochemistry Program and the Chemical Catalysis Program of the NSF Division of Chemistry jointly support the research group of Dr. Rybak-Akimova to study the role of secondary sphere effects, including hydrophobic interactions with sterically bulky substituents and hydrogen bonding, in selected chemical systems. More specifically, this project investigates: (1) O2 binding and activation at sterically protected metal centers capable of multi-electron oxidations (e.g. Pd(0)/Pd(II) or V(III)/V(V)), and the reactivity of thermally unstable end-on dioxygen adducts (metal-superoxo intermediates) compared to analogous stable side-on metal-peroxo species; (2) encapsulation of peroxide guest inside carboxamide cryptand host and the reactivity of this peroxocryptand with externally added oxidants or reductants; (3) generation and reactivity of metal-bound oxygen intermediates in amide-containing three-dimensional cages and analogous "open" tripodal or two-dimensional macrocyclic hosts; (4) anion recognition of high-valent peroxy anions (e.g. peroxyvanadates) with amide-containing tripods, macrocycles, and cages for selective substrate oxidations. This research aims to establish the mechanisms of stepwise coordination of dioxygen to low-valent metal centers supported by ligands with controlled level of steric bulk and/or the number and location of proton-donating groups at the periphery, measure the reactivity of these species with externally added substrates in direct double-mixing kinetic experiments, identify competent oxidants, examine steric and H-bonding modulation of peroxide reactivity encapsulated in metal-free hosts in reactions with external oxidants or reductants, and determine the mechanisms of electron transfer and atom transfer. Stopped-flow instrumentation and expertise in technically demanding kinetic measurements of rapid reactions developed at Tufts continues to have significant impact on the infrastructure for mechanistic research.