Abstract：Water helicity is ubiquitous in biological architectures (e.g., proteins and enzymes) and plays a crucial role in hierarchical chirality transfer. However, achieving water helicity‑modulated hierarchical inverse chirality transfer (e.g., molecular chirality to water helicity and ultimately to nanoscale chirality opposite to that of water) remains a fundamental challenge, owing to the intricate coupling between water conformation and structural hierarchies. Here we demonstrate that a helical water can be constructed and mediate inverse chirality transfer by rationally designing l‑phenylalanine derivative (LPPF) featuring a geometrically matched carboxyl pocket for water. A two‑step inversion cascade of chirality emerges: the L‑configured molecular stereocenter dictates an M‑helical arrangement of water in carboxyl pocket, which in turn templates the P‑helicity of LPPF nanofibers. This process only requires trace amounts of water, and its absence results in achiral nanobelts and circular dichroism (CD) silence. Besides, the helical water has a crucial influence on the function of P‑nanofibers as indicative by the transformation of spin selectivity from up to down upon in situ removal of helical water. Our findings provide deeper insight into the complexity of chirality transfer by revealing a water‑helicity‑modulated inverse transfer mechanism.

Fig.1 Schematic illustration of water helicity-modulated hierarchical inverse chirality transfer in supramolecular assembly. Water helices form via hydrogen-bonding interactions between water and carboxylic groups, which further induce the formation of P-helical LPPF nanofibers. Water absence results in achiral nanobelts. Moreover, the helical water critically influences the function of the P-helical nanofibers, as evidenced by a reversal in spin selectivity from up to down upon in situ removal of the helical water.

    在生命体系里，水分子并不只是简单溶剂。蛋白质、酶、DNA 水合壳层中，水分子可以形成螺旋排布，深度参与生物内部的手性信息传递。但在人工超分子组装领域，如何人为构筑螺旋水结构，并且完成「分子手性→水螺旋→反向纳米手性」的层级传递，一直是领域内很大的难题。过往很多工作只把水当成溶剂，很少把受限的螺旋水作为手性传递的中间模板。

    本文设计了 L‑苯丙氨酸衍生物 LPPF 分子，构建出几何匹配的羧基氢键口袋，捕获微量水分子，实现了水螺旋调控的层级反向手性转移，同时揭示螺旋水可以直接调控组装体的手性诱导自旋选择性（CISS）功能。相关工作被选为 Angew 的 Very Important Paper。

🧪分子设计：给水分子打造专属手性口袋

• LPPF：两端裸露羧基，能够搭建氢键空腔，结合水分子；
• LPPFM：羧基甲酯化，丧失和水形成氢键的位点，作为对照分子。

    在完全无水的有机溶剂当中，LPPF 可以自组装形成纳米带，但完全没有圆二色 CD 信号。分子本身带有 L‑手性，手性信息却卡在分子尺度，无法向上传递到纳米结构。而仅仅加入体积分数 0.1% 的微量水，体系就发生巨大变化：纳米带转变成右手 P 型螺旋纳米纤维，出现显著的双信号 CD 响应。反观对照组 LPPFM，无论体系加水与否，都会直接形成左手螺旋纤维，组装行为不受水的干预。

对比实验告诉我们：羧基与水分子之间的氢键相互作用，是实现这套特殊手性传递的关键所在。

Fig.2 (a, b) CD spectra of (a) LPPF and (b) LPPFM in different water content, 1.5 mM. (c) g value of LPPF in different water content, 1.5 mM. (d) Time-dependent UV signal of LPPF, 1.5 mM. (e-g) SEM images of LPPF (1.5 mM) in (e) EtOH/MCH (1:9, v/v), (f) EtOH/MCH/H2O (1:9:0.005, v/v/v), (g) EtOH/MCH/H2O (1:9:0.01, v/v/v). Scale bar: 5 µm for e-g, 500 nm for e. (h, i) SEM images of LPPFM in (h) EtOH/MCH (1:9, v/v), (i) EtOH/MCH/H2O (1:9:0.01, v/v/v). Scale bar: 500 nm for h-i. (j-n) Time-dependent TEM of LPPF in EtOH/MCH (1:9, v/v), (j) 20 min, (k) 25 min, (l) 30 min, (m) 35 min, (n) 50 min. Scale bar: 50 nm for j, 100 nm for k, 500 nm for l, 1 µm for m, 2 µm for n. (o-s) Time-dependent TEM of LPPF in EtOH/MCH/H2O (1:9:0.01, v/v/v), (o) 2 min, (p) 12 min, (q) 20 min, (r) zoomed image at 20 min, (s) 50 min. Scale bar: 50 nm for o, 100 nm for p, 500 nm for q,r, 1 µm for s. (t-x) Time-dependent TEM of LPPFM in EtOH/MCH (1:9, v/v), (t) 10 s, (u) 30 s, (v) 1 min, (w) 5 min, (x) 10 min. Scale bar: 200 nm for t, 500 nm for u-w, 1 µm for x.

Fig.3 (a) g value of LPPF in different solvent including MCH, CH, Hexane, Heptane. (b) FTIR spectra of LPPF and LPPFM in EtOH/MCH (1:9, v/v) and EtOH/MCH/H2O (1:9:0.01, v/v/v). (c) DSC of LPPF and LPPFM in EtOH/MCH (1:9, v/v) and EtOH/MCH/H2O (1:9:0.01, v/v/v). (d) Time-dependent CD signal at 310 nm of LPPF in EtOH/MCH (1:9, v/v) at 25 and 40 °C after adding 1% water. (e) Time-dependent CD spectra of LPPF in EtOH/MCH (1:9, v/v) at 40 °C after adding 1% water. (f) Schematic illustration of dynamic transition between belts and helices. (g) XRD of LPPF assemblies in EtOH/MCH/H2O (1:9:0.01, v/v/v) and crystal. (h-i) The unit cell of single crystal for (h) LPPF and (i) LPPFM.

🔍两步级联反转：分子手性→M 型水螺旋→P 型纳米纤维

    结合单晶 X 射线衍射、红外 FTIR、差示扫描量热 DSC、选区电子衍射 SAED，再辅以分子动力学模拟，完整还原了整套手性传递链条：

1. L 构型分子的手性中心，诱导羧基口袋内部水分子通过氢键网络有序排布，生成左手 M 型螺旋水链；
2. M 螺旋水充当模板，引导周围 LPPF 分子堆叠，最终得到右手 P 型螺旋纳米纤维，完成两步级联的反向手性转移。

    简单来说：分子手性先把 M‑螺旋印记赋予水分子；而后螺旋水反过来作为模板，刻印出手性相反的纳米纤维。

    单晶结构直观观测到羧基空腔中连续的 M 型水螺旋；SAED 证明纳米纤维的生长方向和水螺旋链互相平行。MD 模拟进一步验证：无水条件下体系热力学倾向生成非手性纳米带，手性传递被阻断；只有 M‑螺旋水模板存在时，体系才会自发组装得到 P 型螺旋纳米纤维。

Fig.4 (a-d) single crystal of LPPFM, (a) top and side view of LPPFM interacted by hydrogen bonds between amide units, (b) the packing detail of LPPFM along a-o-c plane, (c) the noncovalent formed by ester bonds, (d) the π interactions between biphenyl cores and phenyl units. (e-j) single crystal of LPPF, (e) top and side view of LPPF interacted by hydrogen bonds between amide units, (f) the packing detail of LPPF along a-o-c plane, (g) the hydrogen-bonding networks between water and carboxylic groups. (h) the π interactions between biphenyl cores and phenyl units. (i-j) the water helices in LPPF crystal. (k) SAED pattern of LPPF helices and its TEM image.

Fig.5 (a) ss NMR of LPPF dried from EtOH/MCH (1:9, v/v) and EtOH/MCH/H2O (1:9:0.01, v/v/v). (b) 2D SAXS of LPPF assemblies dried from EtOH/MCH (1:9, v/v). (c) NOESY of LPPF assemblies in EtOD-d6/MCH-d14 (7:3, v/v), 3 mM. (d-e) top and side views of stacking modes for LPPF without water. (f) hydrogen bonds between amides and carboxylic groups. (g-h) MLPPF-water co-crystal D simulation processes of (g) LPPF without water and (h) LPPF with water. (i) Time-dependent total energy of LPPF with water in MD simulation.

⚡不止是模板！螺旋水直接调控自旋输运功能

   做 CISS 测试的时候，我们观察到一个非常有意思的现象：螺旋水不仅仅是组装的结构模板，更是调控器件功能的活性组分。

1. 无水条件得到的非手性纳米带，几乎观测不到自旋极化；
2. 保留内部螺旋水（干燥 1 h，残余含水量 8%）的 P 螺旋纳米纤维，表现向上自旋选择性，自旋极化率可达 41±11%；
3. 在保持纳米螺旋形貌不变的前提下，原位移除螺旋水（干燥 9 h，水完全脱除），自旋选择性直接发生反转，切换为向下自旋，极化率达到 69±14%。

    形貌没变，只是把嵌入内部的螺旋水拿走，自旋响应就彻底翻转。这给我们一个全新启发：受限的螺旋水分子可以直接作为功能开关，调控手性超分子器件的自旋输运性能。

Fig.6 (a-c) Averaged I–V curves recorded for (a) LPPF from EtOH/MCH (1:9, v/v), (b) LPPF from EtOH/MCH/H2O (1:9:0.01, v/v/v) dried for 1h, (c) LPPF from EtOH/MCH/H2O (1:9:0.01, v/v/v) dried for 9 h. (d-f) Spin of polarization for (d) LPPF from EtOH/MCH (1:9, v/v), (e) LPPF from EtOH/MCH/H2O (1:9:0.01, v/v/v) dried for 1h, (f) LPPF from EtOH/MCH/H2O (1:9:0.01, v/v/v) dried for 24h. (g) Drying time-dependent spin of polarization for LPPF from EtOH/MCH/H2O (1:9:0.01, v/v/v). (h) Drying time-dependent weight loss before 100 °C for EtOH/MCH/H2O (1:9:0.01, v/v/v). (i) Schematic illustration of Water Helicity dependent spin selectivity.

✍️这项工作跳出传统超分子组装只关注有机分子堆叠的思路，将螺旋水作为层级手性传递的核心媒介。

✅ 通过羧基氢键口袋构筑 M 型螺旋水；

✅ 实现 “分子手性‑螺旋水‑纳米组装体” 的反向层级手性传递；

✅ 证实螺旋水可以充当功能开关，调控手性组装体自旋选择性；

✅ 整个过程只需要体系存在微量水即可触发。

该工作不仅帮助我们进一步理解生命体系中水介导手性传播的内在逻辑，也为构建具有复杂层级手性、可动态调控功能的超分子材料开辟了新思路。本工作第一作者为郜来奔，杨凯凯、王哲源、林碧艳、夏婧怡、赵常利、窦晓秋参与本研究，通讯作者为冯传良教授。由衷感谢国家重点研发计划、国家自然科学基金、上海市科委等项目的资助，也感谢所有合作者的支持！

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论文链接：https://doi.org/10.1002/anie.3329596