Functionalization of L-valine derivatives in MOF

As a natural chiral amino acid, derivatives of L-valine exhibit significant potential in the functional design of metal-organic frameworks (MOFs) due to their unique structural features, including amino groups, carboxyl groups, and modifiable side chains. These derivatives can either construct MOF backbones through coordination with metal ions or be introduced as functional ligands into existing MOF structures, endowing the materials with properties such as chiral recognition, catalytic activity, and biocompatibility. Their application explorations mainly focus on the following directions:

I. Construction of Chiral MOFs and Applications in Chiral Separation

The core advantage of L-valine derivatives lies in their inherent chiral centers (α-carbon atoms). By using them as ligands to coordinate with metal ions (e.g., Zn²⁺, Cu²⁺, Zr⁴⁺), MOF materials with chiral pores can be constructed, enabling selective recognition and separation of enantiomers.

Design Strategy: Typically, the carboxyl or amino groups of L-valine are derivatized (e.g., coupled with aromatic compounds to extend ligand length and expand pore size), enhancing the coordination ability with metal ions while preserving the chiral environment. For example, reacting L-valine with phthalic anhydride generates a chiral ligand containing carboxyl groups, which then coordinates with Zn²⁺ to form a three-dimensional MOF. The chiral sites on the pore walls (such as the isopropyl side chain of valine) can selectively adsorb amino acid enantiomers (e.g., D/L-phenylalanine) or chiral drug intermediates (e.g., chiral alcohols) through hydrogen bonding, van der Waals forces, or steric hindrance differences, achieving efficient separation.

Application Features: Compared to traditional chiral separation materials (e.g., chiral chromatographic columns), such chiral MOFs offer advantages of reusability and mild separation conditions (no need for high temperature or pressure), showing potential application value in chiral drug purification in the pharmaceutical industry.

II. Applications in Catalysis: Based on Active Site Regulation

The amino and carboxyl groups of L-valine derivatives can anchor metal active centers (e.g., Pd, Ru, Co) through coordination, while their isopropyl side chains can regulate the selectivity of catalytic reactions via steric effects, enabling the construction of high-efficiency MOF catalysts.

Types of Catalytic Reactions: They excel in asymmetric hydrogenation, carbon-carbon coupling (e.g., Suzuki reaction), and oxidation reactions. For instance, MOFs constructed from L-valine derivatives and Zr⁴⁺, loaded with Pd nanoparticles, can induce enantioselectivity in alkene asymmetric hydrogenation (ee value up to 90% or higher) through the chiral microenvironment in their pores. Additionally, carboxyl groups in the ligands can activate substrates via proton transfer, accelerating the catalytic cycle.

Advantages: The rigid framework of MOFs can fix the spatial configuration of active sites, avoiding the common problem of active center aggregation and deactivation in homogeneous catalysis. Meanwhile, the porous structure facilitates substrate diffusion, improving catalytic efficiency and cycle stability (some MOF catalysts can be reused over 10 times with an activity retention rate exceeding 80%).

III. Construction of Biocompatible MOFs and Biomedical Applications

As a natural amino acid, L-valine and its derivatives have good biocompatibility, making MOFs constructed from them uniquely advantageous in drug delivery, bioimaging, and other fields.

Drug Delivery Systems: The porous structure of MOFs can load hydrophobic drugs (e.g., paclitaxel, doxorubicin) for pH-responsive release (in the acidic tumor microenvironment, coordination bonds in the MOF framework break, releasing the drug). Furthermore, amino groups in valine derivatives can be modified with targeting molecules (e.g., peptides, antibodies) to enhance the selectivity of drugs for diseased cells and reduce toxic side effects.

Bioimaging: By introducing fluorescent groups (e.g., rhodamine) or paramagnetic ions (e.g., Gd³⁺), MOFs constructed from L-valine derivatives can serve as fluorescent imaging or magnetic resonance imaging (MRI) contrast agents. Their biocompatibility reduces toxicity to organisms, making them suitable for in vivo imaging studies.

IV. Challenges and Optimization Directions in Functional Design

Despite the multifaceted potential of L-valine derivatives in MOF functionalization, several limitations remain:

Stability Issues: Some MOFs based on L-valine derivatives are prone to backbone dissociation in water or acidic environments. This can be addressed by modifying ligands (e.g., introducing rigid aromatic rings to enhance coordination bond strength) or selecting high-charge metal ions (e.g., Zr⁴⁺, Al³⁺) to improve stability.

Pore Size Limitations: MOFs constructed from natural L-valine derivatives typically have small pores (< 1 nm), which are unable to accommodate macromolecular substrates. This can be mitigated by extending ligand length (e.g., coupling with long-chain diacids) or introducing flexible linkers to expand pore size.

Future research needs to further balance the stability, functional activity, and synthesis cost of materials, promoting their translation from laboratory research to practical applications.

Through chiral induction, active site regulation, and biocompatibility design, L-valine derivatives have formed unique advantages in the functional application of MOFs, particularly showing broad prospects in enantiomer separation, asymmetric catalysis, and biomedical fields. Their development relies on in-depth exploration of the structure-activity relationship between ligand structures and MOF properties.