Regiochemical Analysis of the ProTide Activation Mechanism.

ProTides are nucleotide analogues used for the treatment of specific viral infections. These compounds consist of a masked nucleotide that undergoes in vivo enzymatic and spontaneous chemical transformations to generate a free mononucleotide that is ultimately transformed to the pharmaceutically active triphosphorylated drug. The three FDA approved ProTides are composed of a phosphoramidate (P-N) core coupled with a nucleoside analogue, phenol, and an l-alanyl carboxylate ester. The previously proposed mechanism of activation postulates the existence of an unstable 5-membered mixed anhydride cyclic intermediate formed from the direct attack of the carboxylate group of the l-alanyl moiety with expulsion of phenol. The mixed anhydride cyclic intermediate is further postulated to undergo spontaneous hydrolysis to form a linear l-alanyl phosphoramidate product. In the proposed mechanism of activation, the 5-membered mixed anhydride intermediate has been detected previously using mass spectrometry, but the specific site of nucleophilic attack by water (P-O versus C-O) has not been determined. To further interrogate the mechanism for hydrolysis of the putative 5-membered cyclic intermediate formed during ProTide activation, the reaction was conducted in 18O-labeled water using a ProTide analogue that could be activated by carboxypeptidase Y. Mass spectrometry and 31P NMR spectroscopy were used to demonstrate that the hydrolysis of the mixed anhydride 5-membered intermediate occurs with exclusive attack at the phosphorus center.

Exploring Mucoadhesive and Toxicological Characteristics Following Modification of Linear Polyethylenimine with Various Anhydrides.

Linear polyethylenimine (L-PEI) has numerous applications, such as in pharmaceutical formulations, gene delivery, and water treatment. However, due to the presence of secondary amine groups, L-PEI shows a relatively high toxicity and low biocompatibility. Here, various organic anhydrides were used to modify L-PEI to reduce its toxicity and enhance its functionality. We selected methacrylic anhydride, crotonic anhydride, maleic anhydride, and succinic anhydride to modify L-PEI. The structure of the resulting derivatives was characterized using 1H NMR and FTIR spectroscopies, and their behavior in aqueous solutions was studied using turbidimetric and electrophoretic mobility measurements over a broad range of pHs. A fluorescence flow through method determined the mucoadhesive properties of the polymers to the bovine palpebral conjunctiva. Methacrylated L-PEI and crotonylated L-PEI showed strong mucoadhesive properties at pH 7.4, likely due to covalent bonding with mucin thiol groups. In contrast, maleylated and succinylated L-PEI were poorly mucoadhesive as the pH was above their isoelectric point, resulting in electrostatic repulsion between the polymers and mucin. The toxicity of these polymers was evaluated using in vivo assays with planaria and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) cell viability assay in human alveolar epithelial cells. Moreover, the irritancy of polymers was assessed using a slug mucosa irritation assay. The results demonstrated that anhydride modification mitigated the adverse toxicity effects seen for parent L-PEI.

Polyfunctionalized organoselenides: New synthetic approach from selenium-containing cyanohydrins and anti-melanoma activity.

A series of seleno-containing polyfunctionalized compounds was synthesized exploring cyanohydrin chemistry, including α-hydroxy esters, α-hydroxy acids, 1,2-diols, and 1,2-diacetates, with yields ranging from 26 up to 99 %. The cytotoxicity of all synthesized compounds was then evaluated using a non-tumor cell line (BALB/3T3 murine fibroblasts), and those deemed non-cytotoxic had their anti-melanoma activity evaluated using B16-F10 murine melanoma cells. These assays identified two compounds with selective cytotoxic activity against the tested melanoma cell line, showing a potential anti-melanoma application.

Reaction, Recognition, Relay: Anhydride Hydrolysis Reported by Conformationally Responsive Fluorinated Foldamers in Micelles.

Natural membrane receptors are proteins that can report on changes in the concentration of external chemical messengers. Messenger binding to a receptor produces conformational changes that are relayed through the membrane into the cell; this information allows cells to adapt to changes in their environment. Artificial membrane receptors (R)-1 and (S)-1 are helical α-aminoisobutyric acid (Aib) foldamers that replicate key parts of this information relay. Solution-phase 19F NMR spectroscopy of zinc(II)-capped receptor 1, either in organic solvent or in membrane-mimetic micelles, showed messenger binding produced an enrichment of either left- or right-handed screw-sense; the chirality of the bound messenger was relayed to the other receptor terminus. Furthermore, in situ production of a chemical messenger in the external aqueous environment could be detected in real-time by a racemic mixture of receptor 1 in micelles. The hydrolysis of insoluble anhydrides produced carboxylate in the aqueous phase, which bound to the receptors and gave a distinct 19F NMR output from inside the hydrophobic region of the micelles.

Covalent Binding of Reactive Anhydride of Cantharidin to Biological Amines.

Cantharidin is a terpenoid from coleoptera beetles. Cantharidin has been used to treat molluscum contagiosum and some types of tumors. Cantharidin is highly toxic, and cantharidin poisoning and fatal cases have been reported worldwide. The mechanisms underlying cantharidin-induced toxicity remain unclear. Cantharidin contains anhydride, which may react with biologic amines. This study aimed to examine the chemical reactivity of cantharidin toward nucleophiles and characterize adducts of cantharidin with biologic amines in vitro and in mice. Here two types of conjugates were formed in the incubation of cantharidin under physiologic conditions with free amino acids, a mimic peptide, or amine-containing compounds, respectively. Amide-type conjugates were produced by the binding of cantharidin anhydride with the primary amino group of biologic amines. Imide-type conjugates were generated from the dehydration and cyclization of amide-type conjugates. The structure of the conjugates was characterized by using high-resolution mass spectrometry. We introduced the 14N/15N and 79Br/81Br isotope signatures to confirm the formation of conjugates using L-(ε)15N-lysine, L-lysine-15N2, and bromine-tagged hydrazine, respectively. The structure of imide conjugate was also confirmed by nuclear magnetic resonance experiments. Furthermore, the amide and imide conjugates of cantharidin with amino acids or N-acetyl-lysine were detected in mouse liver and urine. Cantharidin was found to modify lysine residue proteins in mouse liver. Pan-cytochrome P450 inhibitor 1-aminobenzotriazole significantly increased the urine cantharidin-N-acetyl-lysine conjugates, whereas it decreased cantharidin metabolites. In summary, cantharidin anhydride can covalently bind to biologic amines nonenzymatically, which facilitates a better understanding of the role of nonenzymatic reactivity in cantharidin poisoning. SIGNIFICANCE STATEMENT: Anhydride moiety of cantharidin can covalently bind to the primary amino group of biological amines nonenzymatically. Amide and imide conjugates were generated after the covalent binding of cantharidin anhydride with the primary amino groups of amino acids, a mimic peptide, and protein lysine residues. The structure of conjugates was confirmed by 14N/15N and 79Br/81Br isotope signatures using isotope-tagged reagents and nuclear magnetic resonance experiments. This study will facilitate the understanding of the role of nonenzymatic reactivity in cantharidin poisoning.

Trapping mechanism by di-d-psicose anhydride with methylglyoxal for prevention of diabetic nephropathy.

Di-d-psicose anhydride (DPA), derived from functional rare saccharide as d-psicose, is investigated for its strong chelating ability. Methylglyoxal (MGO), an important precursor of advanced glycation end-products (AGEs), promotes obesity, and causes complications such as diabetic nephropathy. On mesangial cells, DPA can substantially reduce the negative effects of MGO. DPA effectively trapping MGO in mesangial cells. The bonding properties of the DPA-MGO adduct were discussed by mass spectrometry and nuclear magnetic resonance (NMR). The NMR spectra of the DPA-MGO adduct provide evidence for chelation bonding. The inhibition of AGE formation and the mass spectrometry results of the DPA-MGO adduct indicate that DPA can scavenge MGO at a molar ratio of 1:1. DPA suppressed 330 % of the up-regulated receptor for an AGEs protein expression to a normal level and restored the suppressed glyoxalase 1 level to 86 % of the normal group. This research provides important evidence and theoretical basis for the development of AGE inhibitors derived from rare saccharide.

Dextran Macroinitiator for Synthesis of Polysaccharide-b-Polypeptide Block Copolymers via NCA Ring-Opening Polymerization.

Synthesis of polysaccharide-b-polypeptide block copolymers represents an attractive goal because of their promising potential in delivery applications. Inspired by recent breakthroughs in N-carboxyanhydride (NCA) ring-opening polymerization (ROP), we present an efficient approach for preparation of a dextran-based macroinitiator and the subsequent synthesis of dextran-b-polypeptides via NCA ROP. This is an original approach to creating and employing a native polysaccharide macroinitiator for block copolymer synthesis. In this strategy, regioselective (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) oxidation of the sole primary alcohol located at the C-6 position of the monosaccharide at the nonreducing end of linear dextran results in a carboxylic acid. This motif is then transformed into a tetraalkylammonium carboxylate, thereby generating the dextran macroinitiator. This macroinitiator initiates a wide range of NCA monomers and produces dextran-b-polypeptides with a degree of polymerization (DP) of the polypeptide up to 70 in a controlled manner (D < 1.3). This strategy offers several distinct advantages, including preservation of the original dextran backbone structure, relatively rapid polymerization, and moisture tolerance. The dextran-b-polypeptides exhibit interesting self-assembly behavior. Their nanostructures have been investigated by dynamic light scattering (DLS) and transmission electron microscopy (TEM), and adjustment of the structure of block copolymers allows self-assembly of spherical micelles and worm-like micelles with varied diameters and aspect ratios, revealing a range of diameters from 60 to 160 nm. Moreover, these nanostructures exhibit diverse morphologies, including spherical micelles and worm-like micelles, enabling delivery applications.

Effect of Brønsted Acids on the Activation of Mixed Anhydride/Mixed Carbonic Anhydride and C-Terminal-Free N-Methylated Peptide Synthesis in a Micro-Flow Reactor.

Amidations employing mixed (carbonic) anhydrides have long been favoured in peptide synthesis because of their cost-effectiveness and less waste generation. Despite their long history, no study has compared the effects of additives on the activation of mixed anhydrides and carbonic anhydrides. In this study, we investigated the amidation of mixed (carbonic) anhydride in the presence of a base and/or Brønsted acids. The use of NMI⋅HCl significantly improved the conversion of the mixed carbonic anhydride, while expediting nucleophilic attacks on the desired carbonyl group. In contrast, in the case of mixed anhydrides, neither the conversion nor the desired nucleophilic attack improved significantly. We developed a C-terminus-free N-methylated peptide synthesis method using mixed carbonic anhydrides in a micro-flow reactor. Fourteen N-alkylated peptides were synthesized in moderate to high yields (55-99 %) without severe racemization (<1 %). Additionally, a significant enhancement in the amidation between mixed carbonic anhydrides and bis-TMS-protected N-methyl amino acids with the inclusion of NMI⋅HCl was observed for the first time. In addition, we observed unexpected C-terminal epimerization of the C-terminus-free N-methyl peptides.

Toward Synthetic Intrinsically Disordered Polypeptides (IDPs): Controlled Incorporation of Glycine in the Ring-Opening Polymerization of N-Carboxyanhydrides.

Intrinsically disordered proteins (IDPs) do not have a well-defined folded structure but instead behave as extended polymer chains in solution. Many IDPs are rich in glycine residues, which create steric barriers to secondary structuring and protein folding. Inspired by this feature, we have studied how the introduction of glycine residues influences the secondary structure of a model polypeptide, poly(l-glutamic acid), a helical polymer. For this purpose, we carried out ring-opening copolymerization with γ-benzyl-l-glutamate and glycine N-carboxyanhydride (NCA) monomers. We aimed to control the glycine distribution within PBLG by adjusting the reactivity ratios of the two NCAs using different reaction conditions (temperature, solvent). The relationship between those conditions, the monomer distributions, and the secondary structure enabled the design of intrinsically disordered polypeptides when a highly gradient microstructure was achieved in DMSO.

Utility of Triethyloxonium Tetrafluoroborate for Chloride Removal during Sarcosine N-Carboxyanhydride Synthesis: Improving NCA Purity.

The clinical translation of polysarcosine (pSar) as polyethylene glycol (PEG) replacement in the development of novel nanomedicines creates a broad demand of polymeric material in high-quality making high-purity sarcosine N-carboxyanhydride (Sar-NCA) as monomer for its production inevitable. Within this report, we present the use of triethyloxonium tetrafluoroborate in Sar-NCA synthesis with focus on amino acid and chloride impurities to avoid the sublimation of Sar-NCAs. With a view towards upscaling into kilogram or ton scale, a new methodology of monomer purification is introduced by utilizing the Meerwein's Salt triethyloxonium tetrafluoroborate to remove chloride impurities by covalent binding and converting chloride ions into volatile products within a single step. The novel straightforward technique enables access to monomers with significantly reduced chloride content (<100 ppm) compared to Sar-NCA derived by synthesis or sublimation. The derived monomers enable the controlled-living polymerization in DMF and provide access to pSar polymers with Poisson-like molecular weight distribution within a high range of chain lengths (Xn 25-200). In conclusion, the reported method can be easily applied to Sar-NCA synthesis or purification of commercially available pSar-NCAs and eases access to well-defined hetero-telechelic pSar polymers.

A pentameric TRPV3 channel with a dilated pore.

Transient receptor potential (TRP) channels are a large, eukaryotic ion channel superfamily that control diverse physiological functions, and therefore are attractive drug targets1-5. More than 210 structures from more than 20 different TRP channels have been determined, and all are tetramers4. Despite this wealth of structures, many aspects concerning TRPV channels remain poorly understood, including the pore-dilation phenomenon, whereby prolonged activation leads to increased conductance, permeability to large ions and loss of rectification6,7. Here, we used high-speed atomic force microscopy (HS-AFM) to analyse membrane-embedded TRPV3 at the single-molecule level and discovered a pentameric state. HS-AFM dynamic imaging revealed transience and reversibility of the pentamer in dynamic equilibrium with the canonical tetramer through membrane diffusive protomer exchange. The pentamer population increased upon diphenylboronic anhydride (DPBA) addition, an agonist that has been shown to induce TRPV3 pore dilation. On the basis of these findings, we designed a protein production and data analysis pipeline that resulted in a cryogenic-electron microscopy structure of the TRPV3 pentamer, showing an enlarged pore compared to the tetramer. The slow kinetics to enter and exit the pentameric state, the increased pentamer formation upon DPBA addition and the enlarged pore indicate that the pentamer represents the structural correlate of pore dilation. We thus show membrane diffusive protomer exchange as an additional mechanism for structural changes and conformational variability. Overall, we provide structural evidence for a non-canonical pentameric TRP-channel assembly, laying the foundation for new directions in TRP channel research.

The Use of Aryl-Substituted Homophthalic Anhydrides in the Castagnoli-Cushman Reaction Provides Access to Novel Tetrahydroisoquinolone Carboxylic Acid Bearing an All-Carbon Quaternary Stereogenic Center.

Novel aryl-substituted homophthalic acids were cyclodehydrated to the respective homophthalic anhydrides for use in the Castagnoli-Cushman reaction. With a range of imines, this reaction proceeded smoothly and delivered hitherto undescribed 4-aryl-substituted tetrahydroisoquinolonic acids with remarkable diastereoselectivity, good yields and no need for chromatographic purification. These findings significantly extend the range of cyclic anhydrides employable in the Castagnoli-Cushman reaction and signify access to a novel substitution pattern around the medicinally relevant tetrahydroisoquinolonic acid scaffold.

Precision Synthesis of Polypeptides via Living Anionic Ring-Opening Polymerization of N-Carboxyanhydrides by Tri-thiourea Catalysts.

The chemistry of α-amino acid N-carboxyanhydrides (NCAs) has a history of over 100 years, but precise and efficient ring-opening polymerization methods for NCAs remain highly needed to facilitate the studies of polypeptides─that is, mimics of natural proteins─in various disciplines. Moreover, the universally accepted NCA polymerization mechanisms are largely limited to the "amine" and the "activated monomer" mechanisms, and the anionic ring-opening polymerization of NCAs has so far not been invoked. Herein, we show an unprecedented anion-binding catalytic system combining tripodal tri-thiourea with sodium thiophenolate that enables the fast and selective anionic ring-opening polymerization of NCAs. This method leads to the precision construction of various polypeptides with living polymerization behavior and is evidenced by narrow molecular weight distributions (Mw/Mn < 1.2), chain extension experiments, and minimal "activated monomer" pathway. Calculations and experimental results elucidate a living anionic polymerization mechanism, and high selectivities for monomer propagation relative to other deleterious side reactions, such as the "activated monomer" pathway, are attributed to the enhanced stabilization of the propagating carbamate anion, which is enforced by an intramolecular hydrogen bond within the tri-thiourea structure.

New reagent space and new scope for the Castagnoli-Cushman reaction of oximes and 3-arylglutaconic anhydrides.

The Castagnoli-Cushman reaction of oximes, discovered originally for homophthalic anhydride, stimulated the search for other cyclic anhydrides that would be workable in that reaction. Finally, 3-arylglutaconic acid anhydrides were identified as displaying the right reactivity towards a wide range of oximes (including those which did not react with homophthalic anhydride, such as derivatives of aliphatic aldehydes or ketones and substrates with nucleophilic side groups) and delivering, after 18 h at 110 °C in DMSO, ß,γ-unsaturated N-hydroxylactam products lacking the carboxylic acid functionality as the result of decarboxylation accompanying the cyclocondensation process. The reaction was found to be scalable to gram quantities of the starting anhydrides. The products were shown to be easily amenable to post-condensational double-bond transposition or reduction. As expected from cyclic hydroxamic acids, the reaction products were shown to bind Fe(III) and Cu(II) ions (selectively out of a panel of 16 metal cations) and potentially serve as fluorescent metal sensors.

Preparation of macroporous rigid agarose microspheres by pre-crosslinking with cyclic anhydride.

In this study, a new method for preparing macroporous rigid agarose microspheres was developed by one-step pre-crosslinking method with cyclic anhydride. Three different cyclic anhydrides, namely, maleic anhydride, succinic anhydride, and glutaric anhydride, were used to pre-crosslink agarose. The reaction temperature and the amount of cyclic anhydride in the pre-crosslinking process were optimized to endow agarose with stronger cross-linking. Under the optimal cross-linking condition, macroporous rigid agarose microspheres with homogeneous particle size were successfully obtained by adjusting emulsification method. Cryo-scanning electron microscopy was used to characterize the morphology of cross-linked agarose gel and microspheres. The addition of cyclic anhydride increased the gel aperture of cross-linked agarose microspheres, thereby making the macropores in the microspheres more dense and enhancing the mass transfer in the particles. Under low pressure, the cross-linked agarose microsphere column can effectively separate model proteins at linear flow rates three times higher than the agarose microsphere column. These results indicate that the developed agarose microspheres are a promising high-speed chromatographic medium.

Synthesis of Carbonyl-Containing Oxindoles via Ni-Catalyzed Reductive Aryl-Acylation and Aryl-Esterification of Alkenes.

Carbonyl-containing oxindoles are ubiquitous core structures present in many biologically active natural products and pharmaceutical molecules. Nickel-catalyzed reductive aryl-acylation of alkenes using aryl anhydrides or alkanoyl chlorides as acyl sources is developed, providing 3,3-disubstituted oxindoles bearing ketone functionality at the 3-position. Moreover, nickel-catalyzed reductive aryl-esterification of alkenes using chloroformate as ester sources is further developed, affording 3,3-disubstituted oxindoles bearing ester functionality at the 3-position. This strategy has the advantages of good yields and high functional group compatibility.

Molecular Design, Preparation, and Characterization of Fluoro-Containing Polyimide Ultrafine Fibrous Membranes with High Whiteness, High Thermal Stability, and Good Hydrophobicity.

Polymeric ultrafine fibrous membranes (UFMs) with high thermal stability and high whiteness are highly desired in modern optoelectronic applications. A series of fluoro-containing polyimide (FPI) UFMs with high whiteness, good thermal stability, and good hydrophobicity were prepared via a one-step electrospinning procedure from the organo-soluble FPI resins derived from a fluoro-containing dianhydride, 4,4'-(hexafluoroisopropylidene) diphthalic anhydride (6FDA), and various diamines containing either pendant trifluoromethyl (-CF3) groups or alicyclic units in the side chains. The obtained FPI UFMs, including FPI-1 from 6FDA and 3,5-diaminobenzotrifluoride (TFMDA), FPI-2 from 6FDA and 2'-trifluoromethyl-3,4'-oxydianiline (3FODA), FPI-3 from 6FDA and 1,4-bis[(4-amino-2-trifluoromethyl)phenoxy]benzene (6FAPB), FPI-4 from 4,4'-bis[(4-amino-2-trifluoromethyl)phenoxy]biphenyl (6FBAB), and FPI-5 from 6FDA and 4'-tert-butyl-cyclohexyl-3,5-diaminobenzoate (DABC) showed whiteness indices (WI) higher than 87.00 and optical reflectance values higher than 80% at the wavelength of 457 nm (R457), respectively. The FPI-5 UFM, especially, showed the highest WI of 92.88. Meanwhile, the prepared PI UFMs exhibited good hydrophobic features with water contact angles (WCA) higher than 105°. At last, the PI UFMs exhibited good thermal stability with glass transition temperatures (Tg) higher than 255 °C, and the 5% weight-loss temperatures (T5%) higher than 510 °C in nitrogen.

Poly(ester-anhydrides) Derived from Esters of Hydroxy Acid and Cyclic Anhydrides.

The alternating architecture and hydrophobic side chains hinder hydrolytic cleavage and anhydride interchange in poly(sebacic acid-ricinoleic acid) (P(SA-RA)), which provides stable polyanhydrides at room temperature. In this report, a series of polyanhydrides were designed to investigate the effect of ester bonds, hydrophobic side chains, phenyl moieties, and their distance from anhydride bonds on their stability and properties. Polyanhydrides with alternating architecture are constructed by the polymerization of ester-diacids prepared from ricinoleic or other hydroxy acids with anhydrides such as succinic, maleic, and phthalic anhydrides. The hydrophobic side chains are designed closer to anhydride bonds to investigate hindrance to hydrolytic cleavage and anhydride interchange. Polyanhydrides were obtained by the activation of ester-diacid using acetic anhydride followed by melt condensation. The reactions were monitored by NMR, Fourier transform infrared (FTIR), and gel permeation chromatography (GPC). The synthesized poly(ester-anhydride)s with a shorter chain length compared to P(SA-RA) were stable at room temperature. The hydrolytic degradation studies reveal that the phenyl moiety present in poly(ricinoleic acid phthalate) (PRAP) and poly(hydroxystearic acid phthalate) (PHSAP) reduces the hydrolysis of anhydride bonds. Poly(hydroxyoctanoic acid succinate) (PHOAS) demonstrates the highest molecular weight of all tested polymers. The results reveal that the presence of hydrophobic side chains, phenyl moieties, and their distance from anhydride bonds significantly improves the stability. These stable polyanhydrides can provide convenience to use in control drug-delivery applications. The in vitro drug release study using ibuprofen shows that polymers with aromatic units such as PRAP and PHSAP establish sustained release, which presents more than 50 and 40% of ibuprofen over a period of 28 days.

Catalytic, asymmetric azidations at carbonyls: achiral and meso-anhydride desymmetrisation affords enantioenriched γ-lactams.

An unprecedented organocatalytic process involving the asymmetric addition of azide to meso-anhydrides has been developed, promoted by novel sulfamide-substituted Cinchona alkaloid-based catalysts. Readily available glutaric anhydrides can be smoothly converted to enantioenriched hemi-acyl azides and from there to either γ-amino acids or γ-lactams.

Aliphatic Polyesters with White-Light Clusteroluminescence.

Single-molecule white-light emission (SMWLE) has many advantages in practical applications; however, the fabrication of SMWLE from nonconjugated luminescent polymers, namely, clusteroluminogens (CLgens), is still a big challenge. Herein, the first example of linear nonconjugated polyesters with SMWLE is reported. Twenty-four kinds of nonconjugated aliphatic polyesters with tunable clusteroluminescence (CL) colors and efficiency were synthesized by the copolymerization of six epoxides and four anhydrides. Experimental and calculation results prove that, at the primary structure level, the balance of structural flexibility and rigidity via adjusting the side-chain length significantly enhances the efficiency of CL without wavelength change. However, altering the chemical structures of the monomer from succinic anhydride to trans-maleic anhydride (MA), cis-MA, and citraconic anhydride (CA), secondary structures of these polyesters change from helix to straight and folding sheet accompanied by gradually red-shifted CL from 460 to 570 nm due to the increase in through-space n-π* interactions, as demonstrated by the computational and experimental results. Then, pure SMWLE with CIE coordination (0.30, 0.32) based on overlapped short-wavelength and long-wavelength CL is achieved in CA-based polyesters. This work not only provides further insights into the emission mechanism of CL but also provides a new strategy to manipulate the properties of CL by regulating the hierarchical structures of CLgens.