Feakes D A, Shelly K, Knobler C B, Hawthorne M F
Department of Chemistry and Biochemistry, University of California, Los Angeles 90024.
Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3029-33. doi: 10.1073/pnas.91.8.3029.
The polyhedral borane ion [n-B20H18]2- reacts with liquid ammonia in the presence of a suitable base to produce an apical-equatorial (ae) isomer of the [B20H17NH3]3- ion, [1-(2'-B10H9)-2-NH3B10H8]3-. The structure of this product has been confirmed by 11B NMR spectroscopy and x-ray crystallography. This species undergoes acid-catalyzed rearrangement to an apical-apical (a2) isomer, [1-(1'-B10H9)-2-NH3B10H8]3-, whose structure has been determined by 11B NMR spectroscopy. The sodium salts of both the ae and the a2 isomers of [B20H17NH3]3- have been encapsulated within small unilamellar liposomes, composed of distearoyl phosphatidylcholine/cholesterol (1:1), and investigated as boron-delivery agents for boron neutron capture therapy (BNCT) of cancer. The biodistribution of boron was determined after the injection of liposomal suspensions into BALB/c mice bearing EMT6 tumors. Both [B20H17NH3]3- isomers exhibited excellent tumor uptake and selectivity at very low injected doses, achieving peak tumor boron concentrations of 30-40 micrograms of B/g of tissue and tumor/blood boron ratios of approximately 5. The enhanced retention of the [B20H17NH3]3- isomers by EMT6 tumors may be attributed to their facile intracellular oxidation to an extremely reactive NH3-substituted [n-B20H18]2- ion, the electrophilic [B20H17NH3]- ion. Both isomers of [B20H17NH3]3- are at least 0.5 V more easily oxidized than other previously investigated species containing 20 boron atoms. In another experiment, [ae-B20H17NH3]3- was encapsulated in liposomes prepared with 5% PEG-2000-distearoyl phosphatidylethanolamine in the liposome membrane. As expected, these liposomes exhibited a longer circulation lifetime in the biodistribution experiment, resulting in the continued accumulation of boron in the tumor over the entire 48-hr experiment and reaching a maximum of 47 micrograms of B/g of tumor.
多面体硼烷离子[n-B₂₀H₁₈]²⁻在合适的碱存在下与液氨反应，生成[B₂₀H₁₇NH₃]³⁻离子的顶-赤道（ae）异构体，即[1-(2'-B₁₀H₉)-2-NH₃B₁₀H₈]³⁻。该产物的结构已通过¹¹B核磁共振光谱和X射线晶体学得到证实。该物种在酸催化下重排为顶-顶（a₂）异构体，即[1-(1'-B₁₀H₉)-2-NH₃B₁₀H₈]³⁻，其结构已通过¹¹B核磁共振光谱确定。[B₂₀H₁₇NH₃]³⁻的ae和a₂异构体的钠盐已被包裹在由二硬脂酰磷脂酰胆碱/胆固醇（1:1）组成的小单层脂质体中，并作为用于癌症硼中子俘获疗法（BNCT）的硼递送剂进行了研究。将脂质体悬浮液注射到携带EMT6肿瘤的BALB/c小鼠体内后，测定了硼的生物分布。两种[B₂₀H₁₇NH₃]³⁻异构体在非常低的注射剂量下均表现出优异的肿瘤摄取和选择性，肿瘤硼浓度峰值达到30 - 40微克硼/克组织，肿瘤/血液硼比率约为5。EMT6肿瘤对[B₂₀H₁₇NH₃]³⁻异构体的保留增强可能归因于它们易于在细胞内氧化为极具反应性的NH₃取代的[n-B₂₀H₁₈]²⁻离子，即亲电的[B₂₀H₁₇NH₃]⁻离子。[B₂₀H₁₇NH₃]³⁻的两种异构体比其他先前研究的含20个硼原子的物种至少更容易氧化0.5 V。在另一个实验中，[ae-B₂₀H₁₇NH₃]³⁻被包裹在脂质体膜中含有5%聚乙二醇-2000-二硬脂酰磷脂酰乙醇胺的脂质体中。正如预期的那样，这些脂质体在生物分布实验中表现出更长的循环寿命，导致在整个48小时实验中硼在肿瘤中持续积累，最高达到47微克硼/克肿瘤。
