本論文即以質譜技術作為基礎，研究有機與無機分子之化學結構影響物理化學現象與生物活性，用以建立化學與生物間之作用效果的結構資料庫。第一部份主要針對環狀胍基衍生之胜肽，探究推或拉電子、疏水性、環張力與掌性互異的結構修飾影響其質譜訊號之強度。六種胍基化試劑分別由二胺基化合物與原碳酸四乙酯在一步環化反應而得，其產率於61 ~ 82 %之間；另與含賴氨酸之胜肽進行胍基化反應，產率於2.1 ~ 76.4 %之間，研判立體障礙降低胍基化反應性。基質輔助雷射脫附游離質譜分析結果，胍基衍生反應分別增強訊號7.6 ~ 15.1倍數之多。由構效關係研判推電子性與疏水性高、環張力小有助於增強質譜訊號；拉電子性與親水性高則反之；掌性異構則無影響。論文的第二部份主要針對多吡啶釕金屬錯合物，研究其於大腸桿菌的生理作用途徑與其配位基的修飾對生物活性之構效關係。定量蛋白質體學研究的結果顯示，錯合物的生長抑制現象與轉譯過程之蛋白作用相關。依據最低抑制濃度試驗、生長曲線測試、凝膠電泳與質譜分析的研究結果，Ru(terpy)(NN)Cl2之抑制能力由強而弱，分別是二牙配位基(NN) 為：bpy > dmbpy > dcbpyH2 ~ debpy。依在膠水解胜肽的質譜分析，發現OmpF可能與錯合物形成鍵結。藉由滲透壓調控OmpF蛋白表現的結果呈現，減少OmpF表現降低錯合物對於細胞生長之抑制能力。此結果證明OmpF為多吡啶釕金屬錯合物進入細胞外膜通透的重要途徑，並可輔助說明配位基的結構修飾對於大腸桿菌生長抑制的構效關係。依據構效關係結果研判，拉電子基的修飾降低釕金屬的鍵結能力，而高陰電性與結構立體障礙則降低多吡啶釕金屬錯合物對於細胞外膜的通透性與對其細胞生長的抑制能力。 The structure-activity relationship (SAR) of organic and inorganic compounds with biomolecules is intensively investigated in this thesis. The physical/chemical properties of these chemicals and their corresponding biological activities are analyzed by mass spectrometry. The first part is to study the formation of cyclic guanidine derivatives in lysine-containing peptides and their sensitivity in MALDI analysis. Six organic signal enhancement agents are synthesized by diamino compounds coupled with tetraethyl orthocarbonate. The yield of cyclization and lysine-specific guanidination reactions were prepared in ranges of 61 ~ 82 % and 2.1 ~ 76.5 % respectively. The enhancement of MALDI signal by cyclic guanidine derivatives is in a ratio of 7.6 ~ 15.1 times that result simplified spectra in tandem MS analysis. Modified structures associated with more electron donating property and hydrophobic characters present higher signal responds in MALDI analysis. The second part is to reveal the metabolism pathways of polypyridyl ruthenium (Ru) complexes in E. Coli. cells from proteomics study. Polypyridyl Ru-complexes are introduced with electron-donating and electron–withdrawing groups to study the inhibition of E. coli cells. By SAR studying, growth inhibitory capacity follows the order bidentate ligands (NN) of Ru(terpy)(NN)Cl2: bpy > dmbpy > dcbpyH2 ~ debpy). Up-regulation of EF-Tu and ribosomal proteins as well as down-regulation of ompF upon the Ru-complexes treatment present in quantitative proteomics study. Further analysis in mass spectrometry show that polypyridyl Ru-complexes are capable of binding to OmpF and EF-Tu proteins. Reduction of OmpF concentration was found to decrease Ru-toxicity which is demonstrated by adding 10% w/v sucrose in growth medium. It suggests that OmpF plays an important role in the Ru-complexes permeability into cells. These results provide an explanation of SAR of polypyridyl ruthenium complexes in transportation and cell-growth inhibition.