Dashwood R, Yamane S, Larsen R
Department of Environmental Biochemistry, University of Hawaii, Honolulu 96822, USA.
Environ Mol Mutagen. 1996;27(3):211-8. doi: 10.1002/(SICI)1098-2280(1996)27:3<211::AID-EM6>3.0.CO;2-H.
Chlorophyllin (CHL), a water-soluble derivative of chlorophyll, forms molecular complexes with heterocyclic amine mutagens in vitro. In a previous study [Dashwood and Guo (1993): Environ Mol Mutagen, 22:164-171], we observed an inverse correlation between the binding constants of several mutagen-CHL complexes and the antimutagenic potency of CHL in the Salmonella assay. The present investigation utilized molecular mechanics methods of energy minimization and spectrophotometric titration to examine structural features of chlorophylls, chlorins, and porphyrins that might be important for complex formation with heterocyclic amines. The exocyclic amine group of the mutagen aligned consistently with acid groups in CHL, suggesting that H-bond or electrostatic interactions facilitate complex formation. Replacement of the exocyclic amine with a nitro group abrogated this specific orientation and raised the minimized energies of the complexes. No relationship was found between complex strength and the specific positions of amine or methyl groups on the mutagen. However, the presence of methyl groups increased the minimized energies and lowered the binding constants of the complexes, perhaps due to partial disruption of pi-pi interaction by steric effects. All of the compounds examined, including chlorophyll a, required the presence of pi-pi interactions to form stable complexes with the heterocyclic amines. In general, the present results were in agreement with the inhibitory potency of each compound in the Salmonella assay, and they provide further support for the hypothesis that chlorophylls in the diet might act as interceptor molecules of food-borne carcinogens and mutagens.
叶绿酸（CHL）是叶绿素的一种水溶性衍生物，在体外可与杂环胺诱变剂形成分子复合物。在之前的一项研究中[达什伍德和郭（1993年）：《环境分子诱变》，22:164 - 171]，我们观察到几种诱变剂 - CHL复合物的结合常数与CHL在沙门氏菌试验中的抗诱变效力呈负相关。本研究利用能量最小化的分子力学方法和分光光度滴定法，来研究叶绿素、二氢卟酚和卟啉的结构特征，这些特征可能对于与杂环胺形成复合物很重要。诱变剂的环外胺基团与CHL中的酸性基团始终保持一致排列，这表明氢键或静电相互作用有助于复合物的形成。用硝基取代环外胺消除了这种特定取向，并提高了复合物的最小化能量。未发现复合物强度与诱变剂上胺基或甲基的特定位置之间存在关联。然而，甲基的存在增加了最小化能量并降低了复合物的结合常数，这可能是由于空间效应部分破坏了π - π相互作用。所有检测的化合物，包括叶绿素a，都需要存在π - π相互作用才能与杂环胺形成稳定的复合物。总体而言，目前的结果与每种化合物在沙门氏菌试验中的抑制效力一致，并且它们为饮食中的叶绿素可能作为食源性致癌物和诱变剂的拦截分子这一假说提供了进一步的支持。
