La Jamie Q-H, Michaelides Alex A, Manderville Richard A
Department of Chemistry, University of Guelph, Guelph, Ontario, Canada.
J Phys Chem B. 2007 Oct 11;111(40):11803-11. doi: 10.1021/jp074620z. Epub 2007 Sep 15.
The prodigiosin natural products contain a common 4-methoxy-pyrromethene chromophore that is attached to a pyrrole A-ring that has its lone-pair nitrogen electrons in conjugation with the pyrromethene entity. This feature is known to play a key role in the biological activities (anticancer, antimicrobial, and immunosuppressive) of the prodigiosins. In an attempt to alter or improve upon the therapeutic potential of the prodigiosins, we have synthesized two new isomeric analogues that contain phenolic A-ring systems (a para (p)-phenol; an ortho (o)-phenol with respect to the pyrromethene) with lone-pair oxygen electrons in conjugation with the pyrromethene chromophore of the natural product. Herein, we report on the optical properties of the phenolic prodigiosin analogues that have been measured using absorbance and steady-state emission spectroscopy. For both analogues absorption measurements in aprotic solvents show that the neutral (L) ligands exist as the enol tautomers with lambda(max) ~ 460 nm, as noted for the parent prodigiosin natural product. However, in polar protic solvents the phenolic derivatives undergo ground-state prototropic tautomerization to generate keto tautomers with lambda(max) ~ 530 nm. This unique feature for a prodigiosin analogue involves proton transfer from the phenolic OH to the pyrromethene N1 proton acceptor atom. Tautomeric equilibrium constants (KT) of 1.4 in 1:4 MeCN/H2O (v/v) have been determined from examination of the absorption spectra. Titration of the o-phenolic derivative with Zn(II) in methanol yielded a 40-fold increase in fluorescence intensity (lambda(max) 542 nm) and generated a new 1:1 complex with Zn(II) with a log K of 5.29, suggesting the potential utility of this analogue to act as a fluorescence probe in a biological matrix to monitor Zn(II) concentrations. Our results demonstrate that phenolic A-ring derivatives of prodigiosins possess some unique properties that may act to enhance the biological properties of the prodigiosin natural products.
灵菌红素类天然产物含有一个常见的4-甲氧基-吡咯并甲川发色团，该发色团连接到一个吡咯A环上，其孤对氮电子与吡咯并甲川实体共轭。已知这一特征在灵菌红素的生物活性（抗癌、抗菌和免疫抑制）中起关键作用。为了改变或提高灵菌红素的治疗潜力，我们合成了两种新的异构体类似物，它们含有酚类A环系统（对（p）-苯酚；相对于吡咯并甲川的邻（o）-苯酚），其孤对氧电子与天然产物的吡咯并甲川发色团共轭。在此，我们报告了使用吸光度和稳态发射光谱测量的酚类灵菌红素类似物的光学性质。对于这两种类似物，在非质子溶剂中的吸收测量表明，中性（L）配体以烯醇互变异构体形式存在，其最大吸收波长（λmax）约为460 nm，这与母体灵菌红素类天然产物的情况相同。然而，在极性质子溶剂中，酚类衍生物会发生基态质子转移互变异构，生成最大吸收波长（λmax）约为530 nm的酮式互变异构体。灵菌红素类似物的这一独特特征涉及质子从酚羟基转移到吡咯并甲川的N1质子受体原子上。通过对吸收光谱的研究，已确定在1:（4体积比）乙腈/水（v/v）中的互变异构平衡常数（KT）为1.4。在甲醇中用锌（II）滴定邻酚衍生物，荧光强度增加了40倍（最大发射波长542 nm），并生成了一种与锌（II）的新的1:1配合物，其log K为5.29，这表明该类似物有可能作为生物基质中的荧光探针来监测锌（II）的浓度。我们的结果表明，灵菌红素的酚类A环衍生物具有一些独特的性质，可能会增强灵菌红素类天然产物的生物学性质。
