引入質子誘導具吡啶環四取代尿素分子折疊之研究

Abstract

我們以 Buchwald amidation 條件成功合成出一系列不同長度之具吡啶環四取代尿素分子 7、 10、 15 及 16，透過 TfOH 將質子引入至分子內，研究其質子化的行為及質子化後構形的喜好。檢驗其質子化前後分子上之吡啶環對位碳的化學位移，皆在10 ppm 左右，證明了上述尿素分子上所有的吡啶環於強酸 TfOH 下皆能達成完全質子化的目標，另外從其最終質子化後之二維氫-氫 Noesy 實驗中觀察到，分子上之吡啶環質子與尿素分子上烷基質子的 NOE 對應關係，證明了質子化後之分子構形會因分子內氫鍵的形成而折疊起來。另一方面我們將掌性分子引入至具吡啶環四取代尿素分子的末端，成功地於圓二色光譜上觀察到末端質子化之中間體及完全質子化後由 pyridinium 環與 pyridinium 環間作用所產生之新的二級結構吸收，進一步確認質子化後之分子構形為螺旋結構。另外在部份質子化之 19-(H+)3•H2O 單晶中，已觀察到一部份連續彎曲的結構，在結構中發現水分子埋藏於兩個分子所圍成的空腔內參與正電荷的穩定。

A series of alternating pyridyl-tetra-cyclicurea oligomers 7, 10, 15 and 16 in different length were successfully synthesized by Buchwald amidation. Investigations on the protonation behaviors and conformational preference of these compounds by proton-induced strategy with TfOH were performed. Upon protonation, the 13C NMR chemical shifts changed to be close to or higher than 10 ppm that confirms the full protonation under TfOH. In addition, the relative NOE correlations between the pyridine rings and urea group were observed in NOESY experiments after protonation which reveals the conformation of protonated oligourea were folded into helical structure by intramolecular hydrogen bonding. By incorporation of chiral amide to the end of oligourea, the partial protonated intermediate on terminal pyridine was observed. Upon further addition of TfOH, a new secondary cotton effect absorption produced between pyridinium rings appeared in the CD spectra. Evidenced by CD measurements, the chiral oligourea can shift the equilibrium between the right- and left-handed helical strands after protonation. The crystal structure of 19-(H+)3.H2O reaveals a successive curved part and water molecules are encapsulated by two folded strands that played a critical role in stabilization of positive charges inside the cavity.