類固醇是廣泛分布於生物界的一大類環戊稠全氫化菲衍生物的總稱，又稱類甾醇、甾族化合物。具有特定固定排列成四環的母核，命名為A,B,C,D環。在生物系統中扮演最重要的角色就是作為激素(荷爾蒙)，結合特定的受體蛋白質產生生理反應，引發基因轉錄及細胞功能的改變。

類固醇可結合起作用的細胞內受體來影響神經元功能，透過轉錄因子和調節基因表達。例如孕烯醇酮，是所有同化激素的前體、亦是膽固醇的衍生物，可以調節神經元活動影響睡眠和記憶、甚至結合雄激素受體激活癌症生長。孕烯醇酮的結構-功能活性與連接到環側鏈上的官能基種類有重大的關係。近期，合成孕烯醇酮衍生物受到了關注，在各種條件下被大量研究。

在生物學系統中，金屬陽離子參與人體中許多重要的化學過程。已知金屬離子或含金屬配體會參與類固醇的代謝，並與類固醇螯合。鈣和鋅都會去影響其在體內的作用與分佈。例如，鈣會與碳-20羥基化的孕烯醇酮衍生物絡合而減少平滑肌細胞的鬆弛;鋅則會結合類固醇受體形成協同作用，促進睪酮在人體內的合成。

因此，在此研究中，深入探討了各種孕烯醇酮與金屬陽離子的作用，以更好地了解其在分子水平上的螯合特異性。為此，我們合成了一系列的孕烯醇酮衍生物1-6，針對其側鍊碳-3或碳-17中進行了修飾，並透過與三種人體含量相對豐富的鎂、鈣和鋅金屬二價陽離子的培養;在不同濃度下的實驗，利用1H、13C核磁共振儀去探討類固醇/陽離子的螯合相互作用機制。結果顯示了金屬陽離子與孕烯醇酮分子的某些官能團螯合，意味著與不同金屬陽離子間的特定相互作用。本文針對人體內的類固醇/陽離子復合物，奠定了有效絡合作用的結構特徵研究。

Steroids are a general term for large group of cyclopentadiene-perhydrophenanthrene derivatives widely distributed in the biosphere, also known as sterols and steroidal compounds. The mother nucleus having a rigid arrangement of four rings, which labeled as the A-, B-, C- and D-rings, respectively. The most important role in biological systems is play to act as hormones that bind with specific protein receptors, in order to produce physiological responses for triggering gene transcription in cell function.

Steroids can also bind with the intracellular receptors to influence neuronal functions through transcription factors that regulate the expression of gene. For example, pregnenolone, is a precursor of all anabolic hormones and a derivative of cholesterol which regulates neuronal activity. It was shown that it can affect sleep and memory, and also bind to androgen receptors that activate the growth of cancer cells. The structural-functional activity of pregnenolone is closely related to types of the side chains that attached to the ring. Recently, the synthetic pregnenolone derivatives have been attracted many attentions in this field.

In biological systems, metal cations are involved in many important biochemical processes in the human body. It is well known that metal ions or metal-containing ligands will participate in the metabolism of steroids and chelation with steroids. Both calcium and zinc ions play an important role in the physiochemical action of organisms and cells. For examples, calcium ions form complex with pregnenolone derivatives via C-20 hydroxylated (α-hydroxy ketone) to reduce the relaxation in smooth muscle cells. And zinc ions can interact steroid receptors via a synergistic effect and promote the synthesis of testosterone in the human body.

In this study, we aimed to explore metal cation chelation with various pregnenolone for better understanding its chelation specificity at the molecular level. To this end, we synthesized a series of pregnenolone derivatives 1-6 with modifications of its side chain at C-3 or C-17. And these derivatives were incubated with three kinds of divalent metal cations, i.e. magnesium, calcium, and zinc, which are relatively abundant in human body, to test under different concentrations. Here we applied 1H and 13C NMR spectroscopy to investigate the steroid/metal cation chelation in order to uncover the specific chelation mechanism. Our results demonstrate that metal cations chelate with certain functional groups of pregnenolone molecules, implying specific interactions with respect to different metal cations. This study lays an important structural investigation for better understanding steroid/cations complex formation in the human body.

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