Investigations of Metal-Coordinated Peptides as Supramolecular Synthons

This article describes the synthesis and controlled assembly of four model biological-hybrid scaffolds
via coordination of a metal complex to four new tripeptides. Each model tripeptide investigated has
either a central pyridyl glycyl or a pyridyl alanyl residue between two terminally protected glycines. All
tripeptides were coordinated to their complementary recognition unit, a p-methoxy SCS−Pd pincer
complex. The assembly events were fully characterized and investigated by 1H NMR, ES-MS, and
isothermal titration calorimetry (ITC) to elucidate how the substitution and spatial distance of the pyridyl
moiety to the peptide backbone affects the metal coordination. Using these characterization techniques,
we have shown that the metal-coordination events in all cases are fast and quantitative and that the
peptide backbones do not interfere with the self-assembly. The ITC analyses showed that the 4-pyridyl
tripeptides are the tightest binding ligands toward the palladated pincer complexes with the alanyl derivative
being the strongest overall, demonstrating the superiority of the 4-pyridyl peptides over their 3-pyridyl
analogues. The measured association constants are comparable to other pincer−pyridine systems in DMSO
suggesting that the controlled coordination of the metalated pincer/pyridine interaction is an interesting
biological synthon and will allow for the future development of important noncovalent peptide-based
hybrid materials.

本文报道了通过金属配合物与四种新型三肽的配位作用，合成并可控组装四种模型生物杂化支架（biological-hybrid scaffolds）的研究。所考察的每一种模型三肽，均在两个末端保护的甘氨酸之间带有一个中心吡啶基甘氨酰或吡啶基丙氨酰残基。所有三肽均与对应的互补识别单元——对甲氧基SCS-Pd钳形配合物（p-methoxy SCS−Pd pincer complex）进行配位。研究通过氢核磁共振波谱（1H NMR）、电喷雾质谱（ES-MS）以及等温滴定量热法（isothermal titration calorimetry, ITC）对组装过程开展了全面表征与机制探究，以阐明吡啶基片段相对于肽骨架的取代位置与空间距离如何影响金属配位行为。借助上述表征手段，我们证实所有体系中的金属配位反应均为快速且定量的过程，且肽骨架不会干扰自组装过程。等温滴定量热分析结果显示，4-吡啶基三肽与该钯基钳形配合物的结合亲和力最强，其中丙氨酰衍生物的整体结合能力最优，表明4-吡啶基肽的性能优于其3-吡啶基对应物。测得的结合常数与二甲基亚砜（DMSO）中其他钳形-吡啶体系的数值相当，这说明金属化钳形/吡啶相互作用的可控配位是一种极具应用潜力的生物合成子，将为未来开发重要的非共价肽基杂化材料提供可行路径。