Spectroscopic Evidence for Self-Organization of N-Iodoacetylamphotericin B in Crystalline and Amorphous Phases
Spectroscopic Evidence for Self-Organization of N-Iodoacetylamphotericin B in Crystalline and Amorphous Phases
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DOI：
10.1021/jp307873m
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发表时间：
2012-10-25
影响因子：
3.3
通讯作者：
Mackowski, Sebastian
中科院分区：
文献类型：
--
作者：
Gagos, Mariusz;Kaminski, Daniel;Mackowski, Sebastian
本文通过对抗生素黄曲霉素B（AmB）的N-碘乙酰基衍生物（AmB-I）的研究，提出了一种新的分子自组织的思路。这种选择是由与纯AmB相比AmB-I结晶的简单性决定的。本研究主要集中在AmB-Ⅰ的单晶和非晶态的光谱研究。振动、FTIR和拉曼光谱的结果显示了结晶和无定形形式之间的差异，特别是归因于C=O（1700-1730 cm（-1））和C-C-H基团以及C=C-C（约1000 - 1000 cm（-1））的谱带。1010 cm（-1））拉伸振动。通过这些特征带的强度和位置的强烈差异来识别结晶过程。对于AmB-I晶体，由于晶体形式中的氢键增强，羰基带向较低频率偏移。详细的分析表明，在发色团中的C=C-C弯曲变形的区域中的特征带对于结晶形式的AmB-I来说与非晶态中的该带的强度相比特别强。这些发现得到了荧光光谱法结果的证实。我们观察到一个更快的衰减的AmB-I单晶的发射相比，DMSO溶液的AmB-I。有趣的是，无定形形式的荧光衰减需要三个衰减时间来模拟观察到的行为;这些衰减常数中的两个足以估计AmB-I晶体测量的衰减。AmB-I分子的分子组织的证据是从单个AmB-I晶体上的偏振分辨荧光光谱获得的。发射强度的强各向异性与晶体的轴相关，提供了对AmB-I晶体中分子的实际排列的洞察。这些发现与AmB-I晶体中的分子组织有关，对于理解临床使用的药物阿替霉素B的毒性机制至关重要。
In this paper, we propose a new way of thinking about molecular self-organization of the antibiotic amphotericin B (AmB) by examination of its N-iodoacetyl derivative (AmB-I). This choice was dictated by the simplicity of AmB-I crystallization as compared to pure AmB. The studies focus on spectroscopic investigations of the monocrystal and the amorphous state of AmB-I. The results of vibrational, FTIR, and Raman spectroscopy show differences between the crystalline and amorphous forms, in particular for bands attributed to C=O (1700-1730 cm(-1)) and C-C-H groups, as well as C=C-C (ca. 1010 cm(-1)) stretching vibrations. The process of crystallization is identified by strong differences in the intensities and locations of these characteristic bands. For the AmB-I crystals, the carbonyl band is shifted toward lower frequencies as a result of intensified hydrogen bonding in the crystalline form. Detailed analysis indicates that bands in the region characteristic for the C=C-C bending distortion in the chromophore are particularly intense for AmB-I in the crystalline form as compared to the intensity of this band in the amorphous state. These findings are corroborated by the results of fluorescence spectroscopy. We observe a much faster decay of the emission for the AmB-I monocrystal as compared to the DMSO solution of AmB-I. Interestingly, the fluorescence decay in the amorphous form requires three decay times for simulating the observed behavior; two of these decay constants are sufficient for estimating the decay measured for the AmB-I crystals. The proof of the molecular organization of AmB-I molecules is obtained from polarization-resolved fluorescence spectroscopy on a single AmB-I crystal. Strong anisotropy of the emission intensity correlates with the axes of the crystal, providing insight into actual alignment of the molecules in the AmB-I crystals. These findings related to molecular organization in AmB-I crystals are crucial for understanding toxicity mechanisms of the clinically used drug, amphotericin B.