重金屬中毒一直是高度工業化社會日益嚴重的問題。近年來，國際間層出不窮的汞污染包括日本水俁縣發生的有機汞中毒及前幾年的跨國公害糾紛－台塑汞汙泥事件，使得汞汙染對環境及人體的影響成為大家關注的焦點。汞汙染的來源非常多，例如氯鹼、塑膠、電池和電子工業排放的廢水造成的水污染及使用含汞的農藥或肥料則造成土壤汙染乃至垃圾焚化爐、燃煤發電廠對空氣的污染等。由於一般工業產生的無機汞在環境中易透過微生物的作用轉化成有機汞，因此汞污染主要可分為有機汞、無機汞兩大類。無機汞對人體造成的影響主要會引起噁心、嘔吐、腹痛等症狀，長期甚至會對肝或腎造成傷害，通常有機汞比無機汞化合物更容易被人體吸收，毒性更重，在人體滯留時間也更久，其對人體的損害主要在神經及免疫系統相關疾病，也會破壞重要遺傳物質如DNA的結構。目前科學研究上對重金屬中毒的作用機制並無深入了解，也未提出有效的解毒方法，為此，我們系統性地分析並比較有機與無機汞金屬在不同化學環境下和蛋白質間相互之選擇性與化學鍵結，以助於了解與發展中毒及解毒機制的研究。
我們利用量子力學、連續介電方法、水合化學理論等各式理論方法並結合生物資料庫搜尋對有機、無機汞金屬與環境中重要生物分子在不同化學環境之穩定性與化學鍵結進行系統性分析。研究內容將著重於有機與無機汞立體配位化學預測及比較，並進一步計算汞金屬與各生物分子化學鍵之組成(共價性/離子性/分子軌域貢獻)，以及預測各金屬複合物在不同介電環境之熱力學穩定性。

Knowledge of the nature of the bonding in organic and inorganic mercury compounds is important for understanding the mechanism of heavy metal poisoning. Thus, we have computed the Hg□L bond energies and formation free energies of organic and inorganic mercury complexes, [H3C□Hg□L]1+z and [H2O□Hg□L]2+z, with ligands of biological interest are predicted and rationalized using density functional theory. In contrast to the hard and soft acid and base principle, calculation of the Hg-L bond energies in the model organic and inorganic mercury complexes reveals that the soft metal center of Hg(II) prefers N ligands over S ligands. The result that the complexation energies in organic mercury compounds are less stable than inorganic analogues parallels the experimental findings of thermodynamically unstable Hg-C bond and kinetic lability of methylmercury cation. The concept of orbital-symmetry-based energy decomposition has been employed to determine the contributions from σ and π orbital interactions, electrostatics, and Pauli repulsion to the Hg-L bond energy. The calculations indicate that the bonding in the complexes with soft S ligands is more covalent than with hard N ligands by evaluating the electrostatic and the orbital interaction terms between the metal and ligand fragments. This remarkable result may help unravel the contradictory preference of Hg(II) for N ligands over S ligands. The stability of the complexes in different biological environments has been estimated systematically through the dependence of the dielectric constant □. In good agreement with experimentally observed high affinity for soft metal, MeS□□has been found to be the most thermodynamically preferable ligand for both mercury complexes. The factors governing metal cation selectivity by proteins are investigated. The finding that Hg can successfully compete with Zn in more solvent-exposed sites and in the reorganization of coordination modes may help predict the structural changes upon using Hg for determination of protein structures in X-ray crystallography. Moreover, the predicted geometries of organic and inorganic mercury complexes provide valuable knowledge in suggesting potential cellular targets and proposing possible mechanisms for the heavy metal poisoning in living cells for future studies.

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