Kinetic co‐assembly pathway induced chirality inversion along with morphology transition is of importance to understand biological processes, but still remains a challenge to realize in artificial systems. Herein, helical nanofibers consisting of phenylalanine‐based enantiomers (L/DPF) successfully transform into kinetically trapped architectures with opposite helicity through a kinetic co‐assembly pathway. By contrast, the co‐assemblies obtained by a thermodynamic pathway exhibit non‐helical structures. The formation sequence of non‐covalent interactions plays a crucial role in structural chirality of co‐assemblies. For the kinetic pathway, the hydrogen bonding between D/LPF and naphthylamide derivatives forms before π‐π stacking to facilitate the formation of helical structures with inverse handedness. This study may provide an approach to explore chirality inversion accompanied by morphology transition by manipulating the kinetic co‐assembly pathway.

How the three-dimensional (3D) chiral environment affects the biocatalysis remains an important issue, thereby inspiring the development of a microenvironment that highly mimics the natural features of enzyme to guarantee enhanced biocatalysis. In this study, two gelators bearing d/l-phenylalanine as chiral centers are designed to construct the 3D chiral catalytic microenvironment for enhancing the biocatalysis of lipase. Such a microenvironment is programmed through chiral transmission of chirality from molecular chirality to achiral polymers. It shows that the chirality of the microenvironment evidently influences the catalytic efficiency of immobilized lipase inside the system, and the 3D microenvironment constructed by right-handed helical nanostructures can enhance the catalytic activity of lipase inside as high as 10-fold for catalyzing 4-nitrophenyl palmitate (NPP) to 4-nitrophenol (NP) and 1.4-fold for catalyzing lipids to triglycerides (TGs) in 3T3-L1 cells than that of the achiral microenvironment. Moreover, the 3D chiral microenvironment has the merits of good catalytic efficiency, high storage stability, and efficient recyclability. This strategy of designing a 3D chiral microenvironment suitable for biocatalysis will overcome the present limitations of enzymatic immobilization in traditional materials and enhance the understanding of biocatalysis.

Revascularization plays a critical role in the healing of diabetic wounds. Accumulation of advanced glycation end products (AGEs) and refractory multidrug resistant bacterial infection are the two major barriers to revascularization, directly leading to impaired healing of diabetic wounds. Here, an artfully designed chiral gel dressing is fabricated (named as HA-LM2-RMR), which consists of L-phenylalanine and cationic hexapeptide coassembled helical nanofibers cross-linked with hyaluronic acid via hydrogen bonding. This chiral gel possesses abundant chiral and cationic sites, not only effectively reducing AGEs via stereoselective interaction but also specifically killing multidrug resistant bacteria rather than host cells since cationic hexapeptides selectively interact with negatively charged microbial membrane. Surprisingly, the HA-LM2-RMR fibers present an attractive ability to activate sprouted angiogenesis of Human Umbilical Vein Endothelial Cells by upregulating VEGF and OPA1 expression. In comparison with clinical Prontosan Wound Gel, the HA-LM2-RMR gel presents superior healing efficiency in the infected diabetic wound with respect to angiogenesis and re-epithelialization, shortening the healing period from 21 days to 14 days. These findings for chiral wound dressing provide insights for the design and construction of diabetic wound dressings that target revascularization, which holds great potential to be utilized in tissue regenerative medicine.

Chiral inversion of supramolecular assemblies is of great research interest due to its broad practical applications. However, chiral structure transition induced by in situ regulation of building molecules has remained a challenge. Herein, left-handed fibrous assemblies were constructed by C 2-symmetic l -phenylalanine coupled with diethylene glycol (LPFEG) molecules. In situ hydrolyzing terminal diethylene glycol motifs in LPFEG successfully inverted the chirality of the nanofibers from left- to right-handedness. The transition of right-handed fibers into left-handed fibers could also be achieved via hydrolyzing DPFEG molecules. Circular dichroism (CD) spectroscopy, 1D and 2D nuclear magnetic resonance (NMR) spectroscopy, and Fourier transform infrared (FT-IR) spectroscopy revealed that the back-folded achiral diethylene glycol played a vital role in L/DPFEG molecular arrangements and removing terminal diethylene glycol could induce the opposite rotation of molecular assemblies. Thanks to this merit, the enantioselective separation of racemic phenylalanine was obtained and the enantiomeric excess (ee) values could achieve around ±20% after separation. This study not only provides a new strategy to regulate the chiral structure via dynamic modulation of terminal substituents but also presents a promising application in the field of enantioselective separation.

Dynamic transitions of supramolecular assemblies between lower-order structures and higher-order superhelical structures (e.g. double helical DNA, helical biopolymers) are of vital importance in many physiological processes, but still remains a great challenge to be realized in artificial assembled systems. Herein, a novel biphenyl central core symmetrically coupled with phenylalanine groups drives the construction of dynamic super-helix. The rotary packing of biphenyl central units allows π-π stacking under molecular aggregation state, which combines with hydrogen bonding between phenylalanine moieties to contribute the formation of superhelix. Notably, the coordination between carboxyl moieties and metal ions enables the in situ morphological transition between super-helix and nanospheres, which is regulated by redox reaction. The super-helical fibers mimicking extracellular matrix (ECM) exhibit stronger stereospecific interactions to proteins than primary fibers, facilitating the cell adhesion and proliferation. Moreover, the dynamic super-helical fibers as cell culture scaffolds can induce cell release via change of morphology from super-helix to nanospheres. This study