Background-free detection of molecular chirality using a single-color beam

Chirality is a fundamental property in nature. It manifests in various physical, chemical, and biological processes. Chiral molecules do not have a symmetry plane and exist in pairs of left- and right-handed enantiomers. Chiral molecules show strong enantiomeric selectivity. For example, most isomers of chiral drugs exhibit marked differences in biological activities. Therefore, it is vital to identify the molecular chirality. Furthermore, detection of the chiral dynamics in the femtosecond and sub-femtosecond scales can help people understand the underlying physical mechanisms of the chemical reactions.

With the development of ultrafast laser technology, high-order harmonic spectroscopy provides a powerful tool to explore the molecular structure and electron dynamics. In 2015, a collaborative paper by the Université de Toulouse et al. first uses high-harmonic generation from a randomly oriented gas of molecules to probe molecular chirality. However, this work is based on electric–magnetic interaction and generates weak chiral signals leading to low sensitivity. Since 2019, collaborative papers by Technion-Israel Institute of Technology and Max-Born Institute et al. propose several methods based on dynamical symmetry breaking in high harmonic generation exhibiting strong chiral signals and high enantio-sensitivity. However, nearly all of them depend on the non-collinear superposition of multi-color beams, which requires a highly stable coincidence of beams in time and space in the experiment.

Recently, the Ultrafast Optics Laboratory from Huazhong University of Science and Technology led by Professor Peixiang Lu shows that a structured beam generated by an intense linearly polarized single-color beam can yield strong chiral signals in the high harmonic spectrum. This method provides a simpler and more compact experimental setup and shows a background-free and highly sensitive chirality detection. Figure 1 is the schematic of the experimental setup.

Research results were published in Chinese Optics Letters Vol. 20, Issue 10 in 2022 under the title of "Yuhang Chen, Peixiang Lu, et al. Background-free detection of molecular chirality using a single-color beam [Invited]", and was selected as the cover.

The study shows that the linearly polarized single-color beam focused by a lens and a prism will generate the field being elliptically polarized in the plane of propagation, as shown in Fig. 2.

Because the ensemble of randomly oriented chiral molecules lacks mirror symmetry, the selection rules of high harmonic generation are different between the chiral and achiral (racemic) ensembles driven by such a structured beam. The symmetry analysis shows that even harmonics polarized perpendicular to the plane of propagation and odd harmonics polarized parallel to the plane of propagation will emit from chiral ensembles. But for the achiral (racemic) ensembles, only odd harmonics polarized parallel to the plane of propagation emit and even harmonics are forbidden. The results are confirmed by numerical calculations by three-dimensional time-dependent density functional theory (TDDFT), as shown in Fig. 3. Since chiral and achiral signals are completely separated in harmonic order, the chiral signals (even harmonics) are background-free. This leads to extremely high sensitivity to the chirality of the target media. Further, the researchers studied the far-field signals, and the results still remain.

In summary, this work opens the path to background-free and highly sensitive chirality detection using a simple and compact experimental setup. In the follow-up research, the researchers will use this method to study ultrafast chiral dynamics, such as the isomerization of chiral molecules. They will also expand this scheme to liquid and condensed phases and complete the corresponding experiment.

单色结构光，无背景高灵敏分子手性探测

研究背景

手性分子是指与其镜像不能互相重合的具有一定构型的分子，它们通常以成对的左手和右手对映异构体出现。不同对映体之间表现出的性质可能完全不同。例如，作用于生物体内的药物及农药，其药效作用多与它们和体内靶分子间的手性相关。因此，识别探测手性至关重要。此外，对手性气体飞秒、甚至亚飞秒时间尺度的超快动力学探测，也有助于人们研究和理解手性化学反应背后的物理本质。

得益于超快激光技术的发展，高次谐波光谱学的方法为人们探究原子分子结构以及内部电子动力学过程提供了强有力的支撑。

2015年，法国图卢兹大学等单位的合作论文中首次提出了使用高次谐波谱探测分子手性的方法，实现了在飞秒到阿秒的时间尺度探测分子手性结构，及其超快手性动力学过程。但由于其手性响应依赖于电偶极矩与磁偶极矩的干涉相互作用，所以手性信号灵敏度低。

2019年，以色列理工学院、德国马克思波恩所等单位的合作论文中提出了基于动态对称性破缺的方法，成功在高次谐波谱上观测到高灵敏度的手性信号。

然而他们所提出的方法几乎都依赖于多色光束的非共线叠加，这需要在实验中保证光束在时间和空间上高度稳定重合，操作难度高。

研究亮点

针对上述问题，华中科技大学陆培祥教授带领的超快光学实验室提出了一种利用单色光构造的结构光束进行无背景高灵敏分子手性探测的方法，为手性的探测提供了一种更为简单紧凑的实验方案。相关研究成果发表在Chinese Optics Letters= 2022年20卷第10期上（Yuhang Chen, Peixiang Lu, et al. Background-free detection of molecular chirality using a single-color beam [Invited]），并被选为当期封面。

封面展示了由透镜与棱镜聚焦的光束与手性分子相互作用。在该结构光束的驱动下，手性体系的高次谐波谱上将显现出特有的偶次谐波。盘旋在手性分子上的龙，体现出手性体系的同时，也预示着手性体系在该光场的驱动下将如蛟龙出海般脱颖而出，显现出独特性。

图1为该方案的光路示意图。研究发现，当一束线偏光经过透镜和棱镜组后，会在焦点附近产生在传播平面上椭圆极化的光场，如图2所示。

由于手性分子系综不具有镜像对称性，该结构光束与手性分子气体和非手性分子气体（或外消旋体系）作用产生的高次谐波谱的选择定则是不同的。对称性分析表明, 该光场与手性系综相互作用会产生垂直于传播平面偏振的偶次谐波以及平行于传播平面偏振的奇次谐波；而与非手性系综相互作用仅产生平行于传播平面的奇次谐波，不产生偶次谐波。

含时密度泛函（TDDFT）计算验证了分析结果，如图3所示。手性信号（偶次谐波）和非手性信号（奇次谐波）在频率上是完全分离的，手性信号不会受到非手性信号的干扰。通过对偶次谐波的探测，可以对手性进行无背景高灵敏度的探测。该团队还进一步研究了远场传播信号，发现依然显现出近场信号的规律，符合理论预期。

总结和展望

综上所述，该方案可以对分子手性进行无背景高灵敏度的探测，为手性的探测提供了一种更为简单紧凑的实验方案。研究人员下一步将利用该方法开展对超快手性动力学过程的研究，如手性分子的异构化等，并将此方案进一步拓展到液相、凝聚相等领域的研究。