头孢类抗生素在水溶液中的聚合

POLYMERIZATION OF CEPHALOSPORINS IN AQUEOUS SOLUTION

对７种头孢类抗生素：头孢唑肟钠（ＣＺＸ），头孢噻肟钠（ＣＴＸ），头孢曲松钠（ＣＴＲＸ），头孢替安（ＣＴＭ），头孢孟多钠（ＣＭＤ），头孢唑啉钠（ＣＺＬ）和头孢噻吩钠（ＣＬＴ）在水溶液中的聚合行为进行了研究。将头孢类抗生素的水溶液（１０％～５０％）在ＤＥＡＥ－ＳｅｐｈａｄｅｘＡ－２５离子交换色谱柱上，用含ＮａＣｌ０．２～３．０ｍｏｌ·Ｌ－１的磷酸盐缓冲液（ｐＨ７．４～９．４），在室温下进行线性梯度洗脱，在２６０ｎｍ监测，收集各流分。用ＣＤ，ＦＡＢ－ＭＳ和ＮＭＲ等确证洗脱图谱中峰值对应的化合物，发现ＣＭＤ，ＣＺＬ，ＣＬＴ，ＣＴＲＸ和ＣＴＭ在实验条件下没有形成聚合物，ＣＴＸ和ＣＺＸ的水溶液在室温下放置几天可形成二聚物，表明分子中不含自由氨基或含有氨基，但空间或电荷位阻大时，没有聚合物形成。形成的二聚物是由于自由氨基向核进攻另一分子的β－内酰胺环，引起分子间氨解的结果。

The polymerization of 7 cephalosporins, including ceftizoxime Na (CZXj , cefotaximeNa (CTX) . ceftriaxone Na (CTRX),cefotiam 2 HCI (CTM) . eefamandole Na (CMD) i cefazolin Na(CZL) and cefalotln Na (CLT), in aqueous solution has been investigated in relation to their chemicalstructuree. The aqueous solution of cephalosporins was eluted on DEAE-Sephadex A-25 column by a lineargradient of 0.2～ 3. 0 mol . L-1 NaCl (pH 7. 4～9. 4) at ambient temperatute. The ftactions werecharacterized by UV. CD, FAB-MS, and NMR spectrometries. No pelymers were observed from CTM,CTRX, CMD, CZL, and CLT solutions, while CZX and CTX were found to fotm dimers within a fewdays. The dimers were evidently confirmed to form through the intermolecular aminolysis of the β-lactamcarbonyl moiety by the NH2 group in the second molecule. However, the steric and ionic charge hindranceniay have a direct effect on the polymerization.