Departamento de Química Física y Química Inorgánica, Facultad de Ciencias - I.U. CINQUIMA, Universidad de Valladolid, Paseo de Belén 7, Valladolid 47011, Spain.
Research Unit on BioActive Molecules (RUBAM), Departament de Química Biològica, Institut de Química Avançada de Catalunya (IQAC-CSIC), Jordi Girona 18-26, Barcelona 08034, Spain.
Spectrochim Acta A Mol Biomol Spectrosc. 2022 Feb 15;267(Pt 2):120531. doi: 10.1016/j.saa.2021.120531. Epub 2021 Nov 16.
Chirality is determinant for sphingosine biofunctions and pharmacological activity, yet the reasons for the biological chiral selection are not well understood. Here, we characterized the intra- and intermolecular interactions at the headgroup of the cytotoxic anhydrophytosphingosine jaspine B, revealing chirality-dependent correlations between the puckering of the ring core and the formation of amino-alcohol hydrogen bond networks, both in the monomer and the monohydrate. Following the specific synthesis of a shortened 3-carbon side-chain molecule, denoted jaspine B3, six different isomers were observed in a jet expansion using broadband (chirped-pulsed) rotational spectroscopy. Additionally, a single isomer of the jaspine B3 monohydrate was observed, revealing the insertion of water in between the hydroxy and amino groups and the formation of a network of O-H···N-H···O hydrogen bonds. The specific jaspine B3 stereochemistry thus creates a double-faced molecule where the exposed lone-pair electrons may easily catalyze the formation of intermolecular aggregates and determine the sphingosine biological properties.
手性是神经酰胺生物功能和药理活性的决定因素，但生物手性选择的原因尚不清楚。在这里，我们对细胞毒性脱水神经鞘氨醇 Jasplakinolide B 的头部的分子内和分子间相互作用进行了表征，揭示了在单体和一水合物中，环核的构象和氨基-醇氢键网络的形成之间存在与手性相关的相关性。在使用宽带（啁啾脉冲）旋转光谱法进行喷射扩展时，我们观察到一种缩短了 3 个碳侧链的分子（称为 Jasplakinolide B3）的 6 种不同异构体。此外，还观察到 Jasplakinolide B3 一水合物的单一异构体，表明水分子插入到羟基和氨基之间，并形成 O-H···N-H···O 氢键网络。因此，特定的 Jasplakinolide B3 立体化学创造了一种双面分子，其中暴露的孤对电子可能容易催化形成分子间聚集体，并决定神经鞘氨醇的生物学特性。
