Studies in chemotherapy. VII. A theory of the relation of structure to activity of sulfanilamide type compounds
Studies in chemotherapy. VII. A theory of the relation of structure to activity of sulfanilamide type compounds
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DOI：
10.1021/ja01264a055
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发表时间：
1942-07-01
影响因子：
15
通讯作者：
Roblin, RO Jr
中科院分区：
文献类型：
--
作者：
Bell, PH;Roblin, RO Jr
在pH为7的合成培养基中，用大肠杆菌测定了100多种磺胺类化合物的抑菌活性。测定了这两种化合物的酸解离常数。酸常数与抑菌活性的关系图给出了一条平滑的曲线，该曲线随着酸强度的增加而通过最大值。该理论认为，N‘’取代的磺胺衍生物的SO2基团越负，其抑菌能力越大。由于从相邻的N原子上失去一个质子，这个SO2基团的电负性大大增加。因此，任何磺胺的离子形式都应该比分子形式活跃得多。因此抑菌力（以pH 7测量）随着酸强度的增加而增加，直到化合物基本上完全电离。酸强度与N'取代基(R)的电子吸引能力成正比。当这个增加时，R基团倾向于从SO2基团吸引电子，从而降低其电负性。因此，磺酰胺的酸性越强，离子和分子形式的SO2基团的负电荷越少，两种形式的抑菌活性都越低。因此，酸度的进一步增加，超过了影响化合物几乎完全电离所需的酸度，会降低抑菌活性。讨论了该理论的一些有趣的含义，例如通过改变进行测试的pH值来逆转各种化合物的抑菌能力。了解了N‘’取代基的相对电子吸引能力，就有可能首次预测新的磺胺衍生物的抑菌能力。
The bacteriostatic activity of over 100 sulfanilamide-type compounds was determined with Escherichia coli in synthetic medium at pH 7. The acid dissociation constants of the same compounds were also measured. A plot of acid constants vs. bacteriostatic activity gives a smooth curve which passes through a maximum as the acid strength increases. The theory is developed that the more negative the SO2 group of an N''-substrtuted sulfanilamide derivative, the greater is its bacteriostatic power. The elec-tronegativity of this SO2 group is greatly increased by loss of a proton from the adjacent N atom. Therefore the ionic form of any sulfonamide should be much more active than the molecular form. Thus bacteriostatic power (measured at pH 7) increases with acid strength until the compound is essentially completely ionized. Acid strength is proportioned to the electron attracting power of the N'' substituent (R). As this increases, the R group tends to attract electrons away from the SO2 group, thus decreasing its electronega-tivity. Therefore, the more acidic the sulfonamide, the less negative the SO2 group of the ionic and molecular forms and the less the bacteriostatic activity of either form. Thus further increases in acidity beyond that needed to effect approximately complete ionization of the compound decrease bacteriostatic activity. Some interesting implications of the theory are discussed, such as the reversal of the bacteriostatic power of various compounds by altering the pH at which testing is carried out. Knowing something about the relative electron attracting power of the N''-substituent it is possible for the first time to predict the bacteriostatic power of a new sulfanilamide derivative.