Bauer J A
Department of Chemistry, University of Akron, OH 44325-3601, USA.
Anticancer Drugs. 1998 Mar;9(3):239-44. doi: 10.1097/00001813-199803000-00006.
Nitrosylcobalamin, a vitamin B12-based, non-toxic carrier of nitric oxide (NO), has been synthesized, isolated and characterized in vitro. A UV/Vis analysis was performed confirming the reduction of the cobalt atom of hydroxocobalamin (vitamin B12a) with the binding of NO, causing a shift in the absorption spectra of CO3+ (lambdamax=530) to CO2+ (lambdamax=500) with the formation of nitrosylcobalamin. The extinction coefficient (epsilonmax) of nitrosylcobalamin, as calculated, was 4.8 (mM(-1), cm(-1)). An IR analysis determined the v(NO) vibrational frequency at 1652 cm(-1), supporting the binding of NO and suggesting a bent bonding geometry. NO release was maximized utilizing acidic conditions (pH 4.9, 32 degrees C) with a cumulative release of about 4610 nmol of NO in 675 h (calculated half-life of 210 h), representing 39% NO loading based on 11,890 nmol NO, theoretically possible (one NO per molecule of hydroxocobalamin). The cumulative NO release followed first-order kinetics and was pH dependent. NO release was minimal at pH 6.0 and 7.4 (37 degrees C), and undetected at pH 10 (37 degrees C). The possibility for nitrosylcobalamin to deliver NO (the active chemotherapeutic agent) to neoplastic cells is suggested because tumor cells, specifically leukemia cells, possess surface cell receptors for vitamin B12 which is readily utilized in the cellular proliferation process. Nitrosylcobalamin may offer a 'drug targeting' approach as a potential, biologically compatible and selective chemotherapeutic agent.
亚硝酰钴胺素是一种基于维生素B12的一氧化氮（NO）无毒载体，已在体外合成、分离并进行了表征。进行了紫外/可见分析，证实随着NO的结合，羟钴胺素（维生素B12a）的钴原子发生还原，导致CO3+（λmax = 530）的吸收光谱向CO2+（λmax = 500）发生位移，同时形成亚硝酰钴胺素。计算得出亚硝酰钴胺素的消光系数（εmax）为4.8（mM-1·cm-1）。红外分析确定v(NO)振动频率为1652 cm-1，支持NO的结合，并表明其键合几何形状为弯曲型。在酸性条件（pH 4.9，32℃）下，NO释放达到最大值，在675小时内累积释放约4610 nmol NO（计算得出的半衰期为210小时），基于理论上可能的11890 nmol NO（每个羟钴胺素分子一个NO），代表39%的NO负载量。累积NO释放遵循一级动力学且依赖于pH。在pH 6.0和7.4（37℃）时，NO释放量最小，在pH 10（37℃）时未检测到释放。由于肿瘤细胞，特别是白血病细胞，具有维生素B12的表面细胞受体，且该受体在细胞增殖过程中易于利用，因此有人提出亚硝酰钴胺素有可能将NO（活性化疗药物）递送至肿瘤细胞。亚硝酰钴胺素可能作为一种潜在的、生物相容性和选择性化疗药物提供一种“药物靶向”方法。
