破缺對稱性密度泛函理論與對稱性調適叢集組態交互作用法應用於高活性生物分子之電子結構研究

Abstract

Bicyclam是一種HIV coreceptor的拮抗劑，當螫合過渡金屬後，bicyclam的對抗HIV的活性會更強，然而這種雙核過渡金屬分子的基態可能是高自旋態或是破壞性對稱的低自旋態;我們研究了一系列的bicyclam螫合鉻、錳、鐵三種過渡金屬，得到其交換耦合常數 (exchange coupling constant) 分別為-13.9, -6.4, and -12.1 cm-1，而負號則表示這三種雙核過渡金屬的基態為破壞性對稱的低自旋態，此外，我們也計算了這三個bicyclam的EPR實驗的參數。雙-亞硝鐵錯合物是生物體內儲存或運送一氧化氮的形式之一，當最佳化 [(NO)2Fe(NO)2]-結構時，發現DFT無法正確描述這類系統，而接續的計算證明強靜態交互作用是DFT失敗的主因，正規分子軌域 (canonical orbital) 顯示其SOMOLUMO的能差是四種雙-亞硝鐵錯合物[(NO)2Fe(NO)2]-, [(I)2Fe(NO)2]-, [(N3)2Fe(NO)2]-, [(SCN)2Fe(NO)2]-中最小的，只有0.308 eV。除了[(NO)2Fe(NO)2]-，其餘雙-亞硝鐵錯合物經由DFT計算的基態都是破壞性對稱BS(3,2)的二重態。除此之外，我們也預測了[(CN)2Fe(NO)2]-的結構，氰根對於它的配位化學或是氰化物中毒的解毒劑中都扮演重要的角色，經由計算和UV/Vis實驗資料的比對，推測[(CN)2Fe(NO)2]-構形可能較為接近C2v的對稱性。

Bicyclam compounds exhibit drug activity as CXCR4 (HIV coreceptor) antagonist. While coordinated with two transition metals, the bicyclam molecules demonstrate gain more pharmaceutical potency against HIV. However, the bimetallic molecules might relax to broken-symmetry (BS) singlet ground state rather than high-spin ground state. We investigated bicyclam complexes coordinated with Cr, Mn, and Fe atoms, and their calculated exchange coupling constants (J) are -13.9, -6.4, and -12.1 cm-1, respectively. The negative J values reveal the nature of BS singlet ground state of these molecules. The EPR parameters are also evaluated and compared with experimental data. The dinitrosyl iron complexes (DNICs) are known as a form for the storage and transport of NO in physiological systems. Density functional theories (DFTs) failed in the geometry optimization for the structure of [(NO)2Fe(NO)2]- due to strong static correlation effect. The SOMO-LUMO gap of 0.308 eV is the smallest among the four DNICs studied. Except [(NO)2Fe(NO)2]-, DFTs suggest a doublet ground state with BS(3,2) wavefunction for the other DNICs. In addition, the structure of [(CN)2Fe(NO)2]- is predicted with a Fe-C-N bonding motif. The cyanide (CN-) ligand is important not only in the study of cyanide coordination but in detoxification for cyanide poisoning. The UV/Visible data also imply that the geometry of [(CN)2Fe(NO)2]- adopts nearly C2v symmetry.