Terminal Carboxylic Acid Groups Research Articles

Design, Synthesis, and Evaluation of a New Chemotype Fluorescent Ligand for the P2Y2 Receptor.

The P2Y2 receptor (P2Y2R) is a target for diseases including cancer, idiopathic pulmonary fibrosis, and atherosclerosis. However, there are insufficient P2Y2R antagonists available for validating P2Y2R function and future drug development. Evaluation of how (R)-5-(7-chloro-2-((2-ethoxyethyl)amino)-4H-benzo[5,6]cyclohepta[1,2-d]thiazol-4-yl)-1-methyl-4-thioxo-3,4-dihydropyrimidin-2(1H)-one, a previously published thiazole-based analogue of AR-C118925, binds in a P2Y2R homology model was used to design new P2Y2R antagonist scaffolds. One P2Y2R antagonist scaffold retained millimolar affinity for the P2Y2R and upon further functionalization with terminal carboxylic acid groups affinity was improved over 100-fold. This functionalized P2Y2R antagonist scaffold was employed to develop new chemotype P2Y2R fluorescent ligands, that were attainable in a convergent five-step synthesis. One of these fluorescent ligands demonstrated micromolar affinity (pK d = 6.02 ± 0.12, n = 5) for the P2Y2R in isolated cell membranes and distinct pharmacology from an existing P2Y2R fluorescent antagonist, suggesting it may occupy a different binding site on the P2Y2R.

Vibrational signatures of dynamic excess proton storage between primary amine and carboxylic acid groups.

Ammonium and carboxylic moieties play a central role in proton-mediated processes of molecular recognition, charge transfer or chemical change in (bio)materials. Whereas both chemical groups constitute acid-base pairs in organic salt-bridge structures, they may as well host excess protons in acidic environments. The binding of excess protons often precedes proton transfer reactions and it is therefore of fundamental interest, though challenging from a quantum chemical perspective. As a benchmark for this process, we investigate proton storage in the amphoteric compound 5-aminovaleric acid (AV), within an intramolecular proton bond shared by its primary amine and carboxylic acid terminal groups. Infrared ion spectroscopy is combined with abinitio Molecular Dynamics (AIMD) calculations to expose and rationalize the spectral signatures of protonated AV and its deuterated isotopologues. The dynamic character of the proton bond confers a fluxional structure to the molecular framework, leading to wide-ranging bands in the vibrational spectrum. These features are reproduced with remarkable accuracy by AIMD computations, which serves to lay out microscopic insights into the excess proton binding scenario.

Systematic approach in enhancing the selectivity of titanium tetrabutoxide towards high molecular weight poly(butylene succinate) synthesis

AbstractChemo‐selectivity of titanium tetrabutoxide towards trans‐esterification reaction during polycondensation step in poly(butylene succinate) (PBS) synthesis has been improved by activating the free terminal carboxylic acids in PBS oligomer using trialkyl borates. It is anticipated that the addition of trialkyl borates converts the free terminal carboxylic acid groups in PBS oligoner into a highly reactive acyloxy boron intermediate, which in turn enhances the selectivity of titanium tetrabutoxide towards trans‐esterification reaction to give the corresponding relatively high molecular weight PBS.

Understanding the Reaction of Hydroxy-Terminated Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) Random Copolymers with a Monoisocyanate

This work investigates the reaction kinetics of relatively high molecular weight poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) copolymers containing primary and secondary hydroxyl groups (1°OH and 2°OH) as well as terminal carboxylic acid groups (COOH) with a monoisocyanate. To facilitate their end use in block copolymer synthesis, effects of molecular weight (24–194 kDa), [NCO]/[OHtotal] (1.2–8), and reaction time (4–17 h) were studied. The results show that 1°OH reacted faster than 2°OH, as expected, while the COOH did not react with isocyanate at all under these conditions. Both urethane and allophanate groups were formed. A further reaction of a hydroxy-terminated PHBV (Mn of 27 kDa) with monoisocyanate was undertaken at a ratio of 2.2, with more detailed analysis over time showing the complete reaction of 1°OH and 95 mol % reaction of 2°OH within 4 h at 65 °C. This work is a basis for the potential for controlled PHBV-based block copolymer synthesis.

Thiol-Based Probe Linker with Antifouling Properties for Aptasensor Development

Surfaces with antifouling properties are critical for optimizing biosensors to improve the selectivity and specificity of analyte detection in complex biological samples. This work describes the four-step synthesis of 3-dithiothreitol propanoic acid (DTTCOOH), a new antifouling thiol linker that (a) significantly reduces fouling of raw human serum samples and (b) binds amino receptors via its terminal carboxylic acid group. DTTCOOH was successfully functionalized on quartz crystal microbalance (QCM) discs and used to anchor penicillin-binding aptamers. Relative to bare and coated (11-mercaptoundecanoic acid (MUA) and 1-undecanethiol (UDT)) QCM crystals, DTTCOOH’s antifouling improved by approximately 75–86%. Following aptamer/ethanolamine extension, the modified DTTCOOH layer reduced serum fouling by approximately 95–97% compared to bare and coated (MUA, UDT) crystals. QCM with dissipation (QCM-D) monitoring, contact goniometry, and cyclic voltammetry techniques were used to compare the DTTCOOH surfaces with quartz crystals functionalized with hydrophobic and hydrophilic molecules.

Three New Stigmatellin Derivatives Reveal Biosynthetic Insights of Its Side Chain Decoration.

Myxobacteria generate natural products with unique chemical structures, which not only feature remarkable biological functions, but also demonstrate unprecedented biosynthetic assembly strategies. The stigmatellins have been previously described as potent inhibitors of the mitochondrial and photosynthetic respiratory chain and originate from an unusual polyketide synthase assembly line. While previous biosynthetic investigations were focused on the formation of the 5,7-dimethoxy-8-hydroxychromone ring, side chain decoration of the hydrophobic alkenyl chain in position 2 was investigated less thoroughly. We report here the full structure elucidation, as well as cytotoxic and antimicrobial activities of three new stigmatellins isolated from the myxobacterium Vitiosangium cumulatum MCy10943T with side chain decorations distinct from previously characterized members of this compound family. The hydrophobic alkenyl chain in position 2 of the herein described stigmatellins feature a terminal carboxylic acid group (1), a methoxy group at C-12′ (2) or a vicinal diol (3). These findings provide further implications considering the side chain decoration of these aromatic myxobacterial polyketides and their underlying biosynthesis.

Scaling-up of robust nanofiltration membrane of ultrathin-film-composite structure

Ultrathin film composite nanofiltration membrane was prepared in large-scale (1 m × 50 m) using indigenously developed casting and coating units. A spongy, nano-porous, compaction tolerant substrate layer (middle layer) was formed through judicial selection of the concentrations of base polymer (PSF) and its relative proportion with the pore former (PVP). The substrate with symmetric surface pore morphology (uniform distribution of innumerable nano-pores devoid of macrovoids) facilitated the formation of ultrathin polyamide rejection layer much in the form of laminate (of near uniform thickness) with very limited penetration to the substrate pores. The polyamide layer thickness could be down to 40 nm for the NF/PS/8PVP membrane. XPS study revealed a co-existence of polyamide cross-linked network and linear portion comprised of many sub-units with terminal carboxylic acid groups, which impart surface hydrophilicity and potential. The membranes exhibit a trade-off relationship between flux and selectivity with a flux of 158 L M−2H−1 at 50 psi and Na2SO4 rejection of >99% for NF/PS/8PVP membrane.

Protein-Protein Interaction Inhibitors Targeting the Eph-Ephrin System with a Focus on Amino Acid Conjugates of Bile Acids.

The role of the Eph-ephrin system in the etiology of pathological conditions has been consolidated throughout the years. In this context, approaches directed against this signaling system, intended to modulate its activity, can be strategic therapeutic opportunities. Currently, the most promising class of compounds able to interfere with the Eph receptor-ephrin protein interaction is composed of synthetic derivatives of bile acids. In the present review, we summarize the progresses achieved, in terms of chemical expansions and structure-activity relationships, both in the steroidal core and the terminal carboxylic acid group, along with the pharmacological characterization for the most promising Eph-ephrin antagonists in in vivo settings.

Carboxylic Acid End-Capped Brushes on Titanium via Interface-Mediated RAFT Polymerization and Cell–Surface Interactions

Polymer brushes with tailored surface functionalities are important materials to manipulate the interactions between cells and surfaces in a biomedical context. To enhance the control of the conjugation of cell-adhesive peptides to the polymer brush terminus, poly(di(ethylene glycol)methyl ether methacrylate) (PDEGMA) brushes were fabricated via interface-mediated reversible addition-fragmentation chain transfer (RAFT) polymerization on titanium substrates. Due to the immobilization of 4-((((2-carboxyethyl)thio)carbonothioyl)thio)-4-cyanopentanoic acid as a chain transfer agent (CTA) on the titanium substrates before the subsequent RAFT polymerization, terminal carboxylic acid groups were introduced in the brushes. The brushes obtained were characterized by ellipsometry, static water contact angle measurements, X-ray photoelectron spectroscopy (XPS), and Fourier transform infrared (FT-IR) spectroscopy. PDEGMA brushes allow the facile conjugation of peptides containing the arginine-glycine-aspartic acid (GRGDS) sequence, which afforded the peptide-specific attachment of NIH 3T3 fibroblasts. By contrast, the inhibition of cell attachment was observed on PDEGMA brushes with 7 nm dry thickness conjugated with arginine-alanine-aspartic acid (GRADS). The strategy of surface functional group modification with controllable antifouling or cell-adhesive properties will allow a versatile bio-functionalization approach independent of the underlying surface condition as polymeric biomaterials, among others, in titanium-based medical implant devices.

Synthesis and Aqueous Solution Properties of Shape-Shifting Stimulus-Responsive Diblock Copolymer Nano-Objects

We report the synthesis of poly(N-(2-acryloyloxyethyl)pyrrolidone)-poly(4-hydroxybutyl acrylate) (PNAEP85-PHBAx) diblock copolymer nano-objects via reversible addition–fragmentation chain transfer (RAFT) aqueous dispersion polymerization of 4-hydroxybutyl acrylate (HBA) at 30 °C using an efficient two-step one-pot protocol. Given the relatively low glass transition temperature of the PHBA block, these nano-objects required covalent stabilization prior to transmission electron microscopy (TEM) studies. This was achieved by core crosslinking using glutaraldehyde. TEM analysis of the glutaraldehyde-fixed nano-objects combined with small-angle X-ray scattering (SAXS) studies of linear nano-objects confirmed that pure spheres, worms or vesicles could be obtained at 20 °C in an acidic aqueous solution by simply varying the mean degree of polymerization (x) of the PHBA block. Aqueous electrophoresis, dynamic light scattering and TEM studies indicated that raising the dispersion pH above the pKa of the terminal carboxylic acid group located on each PNAEP chain induced a vesicle-to-sphere transition. 1H NMR studies of linear PNAEP85-PHBAx nano-objects indicated a concomitant increase in the degree of partial hydration of PHBA chains on switching from pH 2-3 to pH 7-8, which is interpreted in terms of a surface plasticization mechanism. Rheological and SAXS studies confirmed that the critical temperature corresponding to the maximum worm gel viscosity could be tuned from 2 to 50 °C by adjusting the PHBA DP. Such tunability is expected to be useful for potential biomedical applications of these worm gels.

Invited Perspective: PFAS Bioconcentration and Biotransformation in Early Life Stage Zebrafish and Its Implications for Human Health Protection.

Invited Perspective: PFAS Bioconcentration and Biotransformation in Early Life Stage Zebrafish and Its Implications for Human Health Protection.

Excited-State Charge Transfer and Extended Charge Separation within Covalently Tethered Type-II CdSe/CdTe Quantum Dot Heterostructures: Colloidal and Multilayered Systems.

We used N,N'-dicyclohexylcarbodiimide (DCC) coupling chemistry to synthesize (1) heterostructures of CdSe and CdTe quantum dots (QDs) in colloidal dispersions and (2) heterostructures of CdSe and CdTe QDs, as well as CdS and CdSe QDs, immobilized on metal oxide thin films. The DCC-mediated formation of amide bonds between terminal carboxylic acid and amine groups of ligands on different QDs drove the formation of heterostructures. This cross-linking mechanism selectively yields heterostructures and prohibits the undesired formation of homostructures consisting of just one type of QD. Products of adsorption, ligand-exchange, and covalent-coupling reactions were characterized by transmission electron microscopy and ATR-FTIR, 1H NMR, electronic absorption, steady-state emission, and time-resolved emission spectroscopy. Ground-state absorption spectra of constituent QDs were unperturbed upon incorporation into heterostructures, enabling control over electronic properties. Heterostructures of CdSe and CdTe QDs exhibit type-II interfacial energetic offsets that promote charge separation following excitation of either QD. Indeed, photoexcited CdTe QDs transferred electrons to CdSe, and photoexcited CdSe QDs transferred holes to CdTe, on time scales of 10-100 ns, as evidenced by dynamic quenching of band-edge and trap-state emission. Mixed dispersions of noninteracting QDs did not undergo excited-state charge transfer. Constructing heterostructures on TiO2 thin films introduced an additional charge-transfer pathway, electron transfer from QDs to TiO2, which occurred on subnanosecond time scales and enabled extended spatial separation of photogenerated electrons and holes. Our results reveal that carbodiimide coupling chemistry can be used to tether colloidal QDs selectively and covalently to each other, yielding dispersed or immobilized heterostructures with programmable compositions and energetic offsets that can undergo efficient excited-state interfacial electron transfer.

Crystal structure of tofacitinib dihydrogen citrate (Xeljanz®), (C16H21N6O)(H2C6H5O7)

The crystal structure of tofacitinib dihydrogen citrate (tofacitinib citrate) has been solved and refined using synchrotron X-ray powder diffraction data, and optimized using density functional techniques. Tofacitinib dihydrogen citrate crystallizes in space group P212121 (#19) with a = 5.91113(1), b = 12.93131(3), c = 30.43499(7) Å, V = 2326.411(6) Å3, and Z = 4. The crystal structure consists of corrugated layers perpendicular to the c-axis. Within the layers, cation⋯anion and anion⋯anion hydrogen bonds link the fragments into a two-dimensional network parallel to the ab-plane. Between the layers, there are only van der Waals contacts. A terminal carboxylic acid group in the citrate anion forms a strong charge-assisted hydrogen bond to the ionized central carboxylate group. The other carboxylic acid acts as a donor to the carbonyl group of the cation. The citrate hydroxy group forms an intramolecular charge-assisted hydrogen bond to the ionized central carboxylate. Two protonated nitrogen atoms in the cation act as donors to the ionized central carboxylate of the anion. These hydrogen bonds form a ring with the graph set symbol R2,2(8). The powder pattern has been submitted to ICDD® for inclusion in the Powder Diffraction File™ (PDF®).

Selective Anchoring Groups for Molecular Electronic Junctions with ITO Electrodes.

Indium tin oxide (ITO) is an attractive substrate for single-molecule electronics since it is transparent while maintaining electrical conductivity. Although it has been used before as a contacting electrode in single-molecule electrical studies, these studies have been limited to the use of carboxylic acid terminal groups for binding molecular wires to the ITO substrates. There is thus the need to investigate other anchoring groups with potential for binding effectively to ITO. With this aim, we have investigated the single-molecule conductance of a series of eight tolane or "tolane-like" molecular wires with a variety of surface binding groups. We first used gold-molecule-gold junctions to identify promising targets for ITO selectivity. We then assessed the propensity and selectivity of carboxylic acid, cyanoacrylic acid, and pyridinium-squarate to bind to ITO and promote the formation of molecular heterojunctions. We found that pyridinium squarate zwitterions display excellent selectivity for binding to ITO over gold surfaces, with contact resistivity comparable to that of carboxylic acids. These single-molecule experiments are complemented by surface chemical characterization with X-ray photoelectron spectroscopy, quartz crystal microbalance, contact angle determination, and nanolithography using an atomic force miscroscope. Finally, we report the first density-functional theory calculations involving ITO electrodes to model charge transport through ITO-molecule-gold heterojunctions.

Directing macrocyclic architecture using iron(III)-, gallium(III)-, or zirconium(IV)-assisted ring closure of linear dimeric endo-hydroxamic acid ligands

Dimeric hydroxamic acid macrocycles are a subclass of bacterial siderophores produced for iron acquisition. Limited yields from natural sources provides the impetus to develop synthetic routes to improve access to these compounds, which have potential utility in metal ion binding applications in the environment and medicine. This work has examined the role of metal ions in forming pre-complexes with linear endo-hydroxamic acid (endo-HXA) ligands bearing terminal amine and carboxylic acid groups optimally configured for in situ ring closure reactions. The 1:1 reaction between Fe(III) and the dimeric endo-HXA ligand 5-((5-(5-((5-aminopentyl)(hydroxy)amino)-5-oxopentanamido)pentyl)(hydroxy)amino)-5-oxopentanoic acid (PPH-PPH) (1) formed the pre-complex (PC) [Fe(PP-PP)-PC]+ with in situ amide coupling generating the macrocycle (MC) [Fe(PP)2-MC]+ and, following Fe(III) removal, the apo-macrocycle 1,13-dihydroxy-1,7,13,19-tetraazacyclotetracosane-2,6,14,18-tetraone (PPH)2-MC (2). The 1:2 reaction system between Fe(III) and the monomeric endo-HXA ligand 5-((5-aminopentyl)(hydroxy)amino)-5-oxopentanoic acid (PPH) gave significantly less [Fe(PP)2-MC]+ than the former system, due to the requirement to form two rather than one amide bond(s). The 1:1 Ga(III):1 system yielded [Ga(PP-PP)-PC]+ and [Ga(PP)2-MC]+. Neither [Zr(PP-PP)-PC]2+ nor [Zr(PP)2-MC]2+ was detected in the 1:1 Zr(IV):1 system. Instead, the Zr(IV) system showed the formation of a 1:2 Zr(IV):1 pre-complex [Zr(PP-PP)2-PC], which following in situ amide bond forming chemistry, generated two Zr(IV) macrocyclic complexes with distinct architectures: a dimer-of-dimers complex [Zr((PP)2)2-MC] and an end-to-end macrocycle [Zr(PP)4-MC]. The formation of [Fe(PP)2-MC]+, [Ga(PP)2-MC]+ or [Zr((PP)2)2-MC] was confirmed from reconstitution experiments with 2. The work has shown that the choice of metal ion in metal-assisted ring closure reactions directs the assembly of macrocyclic complexes with distinct architectures.

Covalent attachment of cobalt (II) tetra-(3-carboxyphenoxy) phthalocyanine onto pre-grafted gold electrode for the determination of catecholamine neurotransmitters

The fabrication of electroactive thin films onto gold electrode surfaces yields very interesting surfaces with excellent electrocatalytic activity. Cobalt (II) tetra-(3-carboxyphenoxy) phthalocyanine (CoTCPhOPc) was successfully synthesized and fully characterized using FT-IR spectroscopy, ultraviolet-visible (UV–Vis) spectroscopy, magnetic circular dichroism (MCD) spectroscopy, elemental analysis, and mass spectrometry. The CoTCPhOPc was immobilized onto phenylethylamino (PEA) pre-grafted gold electrode surface, Au-PEA, using amide coupling reaction to obtain Au-PEA-CoTCPhOPc. This yielded pH sensitive thin films due to the terminal carboxylic acid groups. The Au-PEA-CoTCPhOPc electrode was shown to possess pH-selective properties towards negatively charged [Fe(CN)6]−3/-4 and positively charged [Ru(NH3)6]2+/3+. Au-PEA-CoTCPhOPc electrode surface enabled the detection of catecholamines (dopamine, epinephrine, norepinephrine) and the screening off of ascorbic acid by means of pH functional groups. Excellent electrocatalytic oxidation with the limit of detection (LoD) determined using 3σ was found to be 1.32 (0.95), 3.08 and 2.11 (1.78) μM for electrooxidation and electroreduction (in brackets) of dopamine, epinephrine and norepinephrine; respectively. The limit of quantification (LoQ) was determined using 10σ and found to be 4.41 (3.17), 10.3 and 7.02 (5.93) μM electrooxidation and electroreduction (in brackets) for dopamine, epinephrine and norepinephrine; respectively. The Au-PEA-CoTCPhOPc thin monolayer film was shown to screen off ascorbic acid as no electrocatalytic oxidation was observed for up to 100 μM concentration.

Extending the use of tadalafil scaffold: Development of novel selective phosphodiesterase 5 inhibitors and histone deacetylase inhibitors.

Herein we present the synthesis and characterization of a novel chemical series of tadalafil analogues that display different pharmacological profiles. Compounds that have the 6R, 12aR configuration and terminal carboxylic acid group at the side chain arising from the piperazinedione nitrogen were potent PDE5 inhibitors, with compound 11 having almost equal potency to tadalafil and superior selectivity over PDE11, the most common off-target for tadalafil. Modifying the stereochemistry into 6S, 12aS configuration and adopting the hydroxamic acid moiety as a terminal group gave rise to compounds that only inhibited HDAC. Dual PDE5/HDAC inhibition could be achieved with compounds having 6R, 12aR configuration and hydroxamic acid moiety as a terminal group. The anticancer activity of the synthesized compounds was evaluated against a diverse number of cell lines of different origin. The compounds elicited anticancer activity against cell lines belonging to lymphoproliferative cancer as well as solid tumors. Despite the previous reports suggesting anticancer activity of PDE5 inhibitors, the growth inhibitory activity of the compounds seemed to be solely dependent on HDAC inhibition. Compound 26 (pan HDAC IC50=14nM, PDE5 IC50=46nM) displayed the most potent anticancer activity in the present series and was shown to induce apoptosis in Molt-4 cells. HDAC isoform selectivity testing for compound 26 showed that it is more selective for HDAC6 and 8 over HDAC1 by more than 20-fold.

A Dual Stimuli Responsive Supramolecular Gel Provides Insulin Hydrolysis Protection and Redox‐Controlled Release of Actives

AbstractTwo supramolecular hydrogelators containing a central disulfide moiety and terminal carboxylic acid groups are studied. On the one hand, the hydrogels are responsive to a reductive environment, which transforms the disulfide unit to the corresponding thiols. On the other hand, the hydrogels show pH response associated with the presence of carboxylic acid units. Gels are formed at pH below ≈4 while at higher pH values, ionization of the gelators provokes gel disassembly. The properties of the gel are exploited for the release, as a proof of concept, of Bromophenol Blue in the presence of the reducing species tris(2‐carboxyethyl)phosphine hydrochloride. Additionally, insulin is loaded into the hydrogels and protected from hydrolysis with simulated gastric fluid containing pepsin. Quantitative release of unaltered insulin, checked with an enzyme‐linked immunosorbent assay colorimetric assay, is observed upon treatment with pH 7.4 buffer. This behavior would permit the use of the new hydrogels for oral insulin delivery.

Development, Validation, and Performance of Chitosan-Based Coatings Using Catechol Coupling.

The use of long-lasting polymer coatings on biodevice surfaces has been investigated to improve material-tissue interaction, minimize adverse effects, and enhance their functionality. Natural polymers, especially chitosan, are of particular interest due to their excellent biological properties, such as biocompatibility, non-toxicity, and antimicrobial properties. One way to produce chitosan coating is by covalent grafting with catechol molecules such as dopamine, caffeic acid, and tannic acid, resulting in an attachment ten times stronger than that of simple physisorption. Caffeic acid presents an advantage over dopamine because it allows direct chitosan grafting, due to its terminal carboxylic acid group, without the need of a linking arm, as employed in the dopamine approach. In this study, the grafting of chitosan using caffeic acid, over surfaces or in solution, is compared with dopamine grafting using poly(ethylene glycol) as a linking arm. The following coating properties are observed; covering and homogeneity are assessed by X-ray photoelectron spectroscopy and atomic force microscopy analyses, hydrophilicity with contact angle measurements, stability with aging tests, anticorrosion behavior, and coating non-toxicity. Results show that grafting using caffeic acid/chitosan in solution over a metallic surface may be advantageous, compared to traditional dopamine coating.

Reactive splicing compatibilization of immiscible polymer blends: Compatibilizer synthesis in the melt state and compatibilizer architecture effects

Reactive compatibilization is an effective method to improve the compatibility of immiscible polymer blends. The in-situ-formed graft/block copolymers should be thermodynamically located at the interface to bridge the neighboring phases. Unfortunately, they are often pulled out of the interface because of the asymmetric molecular structures. Here, we propose a new strategy to compatibilize immiscible polymer blends called reactive splicing compatibilization. Poly (styrene-co-glycidyl methacrylate) (SG) with high glycidyl methacrylate (GMA) content is used as the reactive backbone chain. Both poly (l-lactic acid) (PLLA) and poly (butylene adipate-co-terephthalate) (PBAT) molecular chains can be easily grafted onto the SG main backbone by the reaction of the terminal carboxylic acid groups with the epoxide groups in the melt. Direct melt blending SG with PLLA and/or PBAT leads to reactive compatibilizers with various molecular architectures, which are used for subsequent compatibilization of PLLA/PBAT blends. It was found that the compatibilizer architecture significantly affects the compatibilization efficiency. The best compatibilization occurs with a reactive compatibilizer of SG-g-PBAT with the SG to PBAT weight ratio of 1:2. The compatibilized PLLA/PBAT (50/50 w/w) blend has precise co-continuous phase morphology with very few micelles. The blend exhibits extremely high Charpy notched impact strength of 90.2 kJ/m2 and tensile strength of 33.3 MPa. The principle of the facile splicing compatibilization strategy is highly applicable to many other immiscible blends with both components containing reactive groups.