Biomimetic Pathway Research Articles

Assembly-enhanced recognition: A biomimetic pathway to achieve ultrahigh affinities

On the one hand, nature utilizes hierarchical assemblies to create complex biological binding pockets, enabling ultrastrong recognition toward substrates in aqueous solutions. On the other hand, chemists have been fervently pursuing high-affinity recognition by constructing covalently well-preorganized stereoelectronic cavities. The potential of noncovalent assembly, however, for enhancing molecular recognition has long been underestimated. Inspired by (strept)avidin, an amphiphilic azocalix[4]arene derivative capable of assembly in aqueous solutions has been explored by us and demonstrated to exhibit ultrahigh binding affinity (up to 1012 M-1), which is almost four orders of magnitude higher than those reported for nonassembled azocalix[4]arenes. An ultrastable azocalix[4]arene/photosensitizer complex has been applied in hypoxia-targeted photodynamic therapy for tumors. These findings highlight the immense potential of an assembly-enhanced recognition strategy in the development of the next generation of artificial receptors with appropriate functionalities and extraordinary recognition properties.

Biomimetic Aramid Nanofiber/β-FeOOH Composite Coating for Polypropylene Separators in Lithium-Sulfur Batteries.

Aramid nanofibers (ANFs), with attractive mechanical and thermal properties, have attracted much attention as key building units for the design of high-performance composite materials. Although great progress has been made, the potential of ANFs as fibrous protein mimetics for controlling the growth of inorganic materials has not been fully revealed, which is critical for avoiding phase separation associated with typical solution blending. In this work, we show that ANFs could template the oriented growth of β-FeOOH nanowhiskers, which enables the synthesis of ANFs/β-FeOOH hybrids as composite coatings for polypropylene (PP) separators in Li-S batteries. The modified PP separator exhibits enhanced mechanical properties, heightened thermal performance, optimized electrolyte wettability, and improved ion conductivity, leading to superior electrochemical properties, including high initial specific capacity, better rate capability, and long cycling stability, which are superior to those of the commercial PP separators. Importantly, the addition of β-FeOOH to ANFs could further contribute to the suppression of lithium polysulfide shuttling by chemical immobilization, inhibition of the growth of lithium dendrites because of the intrinsic high modulus and hardness, and promotion of reaction dynamics due to the catalytic effect. We believe that our work may provide a potent biomimetic pathway for the development of advanced battery separators based on ANFs.

Intestinal Absorption of Nanoparticles to Reduce Oxidative Stress and Vasoconstriction for Treating Diabetic Nephropathy.

The etiology of diabetic nephropathy (DN) is complex, and the incidence is increasing year by year. The patient's kidney showed oxidative stress damage, increasing active oxygen species (ROS) content, and vasoconstriction. Due to poor drug solubility and low renal accumulation, the current treatment regimens have not effectively alleviated glomerulopathy and other kidney damage caused by DN. Therefore, it is of great significance to explore new treatment strategies and drug delivery systems. Here, we constructed an oral nanodelivery system (Tel/CAN@CS-DA) that reduced oxidative stress and vasoconstriction. Deoxycholic acid (DA)-modified nanoparticles entered into intestinal epithelial cells (Caco2 cells) via the bile acid biomimetic pathway, then escaped from the lysosomes and eventually spat out the cells, increasing the oral absorption of nanoparticles. Chitosan (CS) nanoparticles could achieve renal targeting through specific binding with a renal giant protein receptor and deliver drugs to renal tubule epithelial cells (HK-2 cells). In vitro studies also proved that telmisartan (Tel) and canagliflozin (CAN) effectively removed cellular reactive oxygen species (ROS) and reduced HK-2 cell apoptosis caused by high glucose. In the in vivo model induced by streptozotocin (STZ), the results showed that the nanosystem not only elevated AMPK protein expression, inhibited angiotensin II (Ang II) protein expression to effectively reduce oxidative stress level, dilated renal blood vessels but also reduced the degree of inflammation and fibrosis. Overall, Tel/CAN@CS-DA multifunctional oral nanosystem can effectively treat DN with low toxicity, which provides a new idea for the treatment of DN.

Biomimetic Design of Turbine Blades for Ocean Current Power Generation.

The enhancement of energy technology and innovation play a crucial role in order to meet the challenges related to global warming in the coming decades. Inspired by bird wings, the performance of a bio-inspired blade assembled to a marine turbine model, is examined. Following a biomimetic pathway, the aerodynamic performance of the bird wings of the species Common Guillemot (Uria aalge) was tested in a wind tunnel laboratory. Based on our results, we derived a bio-inspired blade model by following a laser scanning method. Lastly, the bio-inspired blades were assembled to a marine turbine model and tested in a large flow tank facility. We found efficiencies (Cp) up to 0.3 which is around 53% of the maximum power that can be expected from the turbine model according to the Betz approach. Our findings are analyzed in the discussion section as well as considerations for future research.

Asymmetric Total Synthesis of Phomarol

Asymmetric Total Synthesis of Phomarol

Prebiotic synthesis of cysteine peptides that catalyze peptide ligation in neutral water.

Peptide biosynthesis is performed by ribosomes and several other classes of enzymes, but a simple chemical synthesis may have created the first peptides at the origins of life. α-Aminonitriles-prebiotic α-amino acid precursors-are generally produced by Strecker reactions. However, cysteine's aminothiol is incompatible with nitriles. Consequently, cysteine nitrile is not stable, and cysteine has been proposed to be a product of evolution, not prebiotic chemistry. We now report a high-yielding, prebiotic synthesis of cysteine peptides. Our biomimetic pathway converts serine to cysteine by nitrile-activated dehydroalanine synthesis. We also demonstrate that N-acylcysteines catalyze peptide ligation, directly coupling kinetically stable-but energy-rich-α-amidonitriles to proteinogenic amines. This rare example of selective and efficient organocatalysis in water implicates cysteine as both catalyst and precursor in prebiotic peptide synthesis.

A Versatile Boc Solid Phase Synthesis of Daptomycin and Analogues Using Site Specific, On-Resin Ozonolysis to Install the Kynurenine Residue.

A de novo solid-phase synthesis of the cyclic lipodepsipeptide daptomycin via Boc chemistry was achieved. The challenging ester bond formation between the nonproteinogenic amino acid kynurenine was achieved by esterification of a threonine residue with a protected tryptophan. Subsequent late-stage on-resin ozonolysis, inspired by the biomimetic pathway, afforded the kynurenine residue directly. Synthetic daptomycin possessed potent antimicrobial activity (MIC100 =1.0 μg mL-1 ) against S. aureus, while five other daptomycin analogues containing (2R,3R)-3-methylglutamic acid, (2S,4S)-4-methylglutamic acid or canonical glutamic acid at position twelve prepared using this new methodology were all inactive, clearly establishing that the (2S,3R)-3-methylglutamic acid plays a key role in the antimicrobial activity of daptomycin.

The role of precisely matching fascicles in the quick recovery of nerve function in long peripheral nerve defects.

Peripheral nerve injury therapy in the clinic remains less than satisfactory. The gold standard of treatment for long peripheral nerve defects is autologous nerve grafts; however, numerous clinical complications are associated with this treatment. As tissue engineering has developed, tissue-engineered nerve grafts (TENGs) have shown potential applications as alternatives to autologous nerve grafts. To verify the important role of the biomimetic pathway of fascicle design in TENGs, we designed an animal model to study the role of the precise matching of fascicles in the effectiveness of nerve function recovery. 24 Sprague-Dawley rats were divided randomly into three groups (eight/group) that corresponded to 100% fascicle matching (100%FM), 50%FM and 0%FM. We selected Sprague–Dawley rat long-gap (15 mm) sciatic nerve defects. In the 6 weeks after surgery, we found that the 100%FM group showed the most effective functional recovery among the three groups. The 100%FM group showed better functional recovery on the basis of the sciatic functional index than the 50%FM and 0%FM groups. According to histological evaluation, the 100%FM group showed more regenerating nerve fibres. Moreover, in terms of the prevention of muscle atrophy, the 100%FM group showed excellent physiological outcomes. The 100%FM as tissue-engineered scaffolds can enhance nerve regeneration and effective functional recovery after the repair of large nerve defects. The results of this study provide a theoretical basis for future TENG designs including biomimetic fascicle pathways for repairing long nerve defects.

Total synthesis of biologically active alkaloids using bio-inspired indole oxidation

Many tryptophan-based dimeric diketopiperazine (DKP) alkaloids including WIN 64821 and ditryptophenaline, which exhibit fascinating biological activities, have been isolated from fungi. These alkaloids possess a unique architecture; therefore several total syntheses of these compounds have been accomplished via bio-inspired reactions. Despite these elegant strategies, we were convinced that a more direct bio-inspired solution for the preparation of tryptophan-based DKP alkaloids was possible because in a true biosynthesis, direct dimerization of tryptophan occurs in aqueous media without incorporation of a protecting group on the substrates. Thus we developed direct bio-inspired dimerization reactions in aqueous, acidic media, along with a novel biomimetic pathway, to provide C2-symmetric and non-symmetric dimeric compounds from commercially available amine-free tryptophan derivatives using Mn(OAc)3, VOF3, and V2O5 as one-electron oxidants. In addition, concise two-pot or three-step syntheses of the naturally occurring dimeric DKP alkaloids (+)-WIN 64821, (-)-ditryptophenaline, and (+)-naseseazine B were accomplished with total yields of 20%, 13%, and 20%, respectively. The present synthesis has several noteworthy features: 1) the tryptophan-based C2-symmetric and non-symmetric dimeric key intermediates can be prepared on a multigram scale in one step; 2) the developed oxidation reaction was carried out in aqueous, acidic solution without deactivation of the metal oxidants; 3) protection of the primary amine can be avoided by salt formation in aqueous acid; 4) for the total two-pot operation, the reaction media are environmentally friendly water and ethanol; 5) satisfactory total yields are obtained compared with previously reported syntheses.

Cu(ii) conjugation along the transformation of a vitamin K3derivative to a dinaphthoquinone methide radical

1,1′-Methide-bi-vitamin K3 (B) has been isolated as a dinaphthoquinone methide radical (DNQM) by the transformation of 1-imino(acetylhydrazino)-vitamin K3 (A). The transformation follows a biomimetic activation pathway mediated via Cu(II) ion catalyzed oxidative coupling. Single crystal X-ray and electron spin resonance (ESR) experiments combined with density functional calculations elucidate the “resonance structure” of the DNQM radical (B). Fluorescence investigations reveal that DNQM facilitates interaction with the cysteine residue. As compared to the parent substrate, B shows a depletion in the level of GSH, triggering apoptosis in HeLa cells.

Total synthesis of a novel oxa-bowl natural product paracaseolide A via a ‘putative’ biomimetic pathway

A total synthesis of bioactive tetracyclic natural product paracaseolide A, embodying an architecturally unusual oxa-bowl framework, has been accomplished from commercially available 5-methyl-2-furfural. The key step involving a thermal [4+2]-dimerization of an appropriately crafted 5-methyl-3-alkenylbutenolide is shown to proceed in a stepwise manner.

A Biomimetic Pathway for Vanadium‐Catalyzed Aerobic Oxidation of Alcohols: Evidence for a Base‐Assisted Dehydrogenation Mechanism

The first step in the catalytic oxidation of alcohols by molecular O(2), mediated by homogeneous vanadium(V) complexes [LV(V)(O)(OR)], is ligand exchange. The unusual mechanism of the subsequent intramolecular oxidation of benzyl alcoholate ligands in the 8-hydroxyquinolinato (HQ) complexes [(HQ)(2)V(V)(O)(OCH(2)C(6)H(4)-p-X)] involves intermolecular deprotonation. In the presence of triethylamine, complex 3 (X = H) reacts within an hour at room temperature to generate, quantitatively, [(HQ)(2)V(IV)(O)], benzaldehyde (0.5 equivalents), and benzyl alcohol (0.5 equivalents). The base plays a key role in the reaction: in its absence, less than 12% conversion was observed after 72 hours. The reaction is first order in both 3 and NEt(3), with activation parameters ΔH(≠)=(28±4) kJ mol(-1) and ΔS(≠)=(-169±4) J K(-1) mol(-1). A large kinetic isotope effect, 10.2±0.6, was observed when the benzylic hydrogen atoms were replaced by deuterium atoms. The effect of the para substituent of the benzyl alcoholate ligand on the reaction rate was investigated using a Hammett plot, which was constructed using σ(p). From the slope of the Hammett plot, ρ=+(1.34±0.18), a significant buildup of negative charge on the benzylic carbon atom in the transition state is inferred. These experimental findings, in combination with computational studies, support an unusual bimolecular pathway for the intramolecular redox reaction, in which the rate-limiting step is deprotonation at the benzylic position. This mechanism, that is, base-assisted dehydrogenation (BAD), represents a biomimetic pathway for transition-metal-mediated alcohol oxidations, differing from the previously identified hydride-transfer and radical pathways. It suggests a new way to enhance the activity and selectivity of vanadium catalysts in a wide range of redox reactions, through control of the outer coordination sphere.

ChemInform Abstract: Selectivity in Reduction of Natural Furanoheliangolides with Stryker′s Reagent.

AbstractNatural sesquiterpene lactones (I) and (IV), and the ether derivatives (VII) and (X) are chemoselectively reduced through a biomimetic pathway affording eremantholides (II) and (V), and the corresponding derivatives (VIII) and (XI).

Total Synthesis of (±)‐Decursivine and (±)‐Serotobenine: A Witkop Photocyclization/Elimination/O‐Michael Addition Cascade Approach

A photo op: The concise total syntheses of (±)-decursivine and (±)-serotobenine were achieved by using the titled cascade reaction, which is modeled on the biomimetic pathway. The synthesis of (±)-decursivine, which exhibits antimalarial activity, was carried out in five steps without using protecting groups.

Biomimetic Synthesis of Hyperolactones

Through a biomimetic pathway, hyperolactone D, 4-hydroxyhyperolactone D, and hyperolactone C were synthesized from methyl acetoacetate via Weiler's dianion method, asymmetric allylic alkylation, biomimetic lactonization, oxidation, and cyclization. The stereochemistry of the quaternary carbon was controlled efficiently by Palladium-catalyzed asymmetric allylic alkylation. This strategy was also used for the synthesis of hyperolactone B.

Selectivity in reduction of natural furanoheliangolides with Stryker's reagent

Reduction of the natural sesquiterpene lactones furanoheliangolides with Stryker's reagent is an effective process for producing eremantholides through a biomimetic pathway. Other reduction products are also formed. Oxygenated functions at C-15 of the furanoheliangolide produce an increase in the velocities of the reactions and reduce the chemoselectivity of the reagent.

Photocatalytic Hydrogen Evolution from Rhenium(I) Complexes to [FeFe] Hydrogenase Mimics in Aqueous SDS Micellar Systems: A Biomimetic Pathway

To offer an intriguing access to photocatalytic H(2) generation in an aqueous solution, the hydrophobic photosensitizer, Re(I)(4,4'-dimethylbpy)(CO)(3)Br (1) or Re(I)(1,10-phenanthroline)(CO)(3)Br (2), and [FeFe] H(2)ases mimics, [Fe(2)(CO)(6)(mu-adt)CH(2)C(6)H(5)] (3) or [Fe(2)(CO)(6)(mu-adt)C(6)H(5)] (4) [mu-adt = N(CH(2)S)(2)], have been successfully incorporated into an aqueous sodium dodecyl sulfate (SDS) micelle solution, in which ascorbic acid (H(2)A) was used as a sacrificial electron donor and proton source. Studies on the reaction efficiency for H(2) generation reveal that both the close contact and the driving force for electron transfer from the excited Re(I) complexes and [FeFe] H(2)ases mimics are crucial for efficient H(2) generation with visible light irradiation. Steady-state and time-resolved investigations demonstrate that the electron transfer takes place from the excited Re(I) complex 1 or 2 to [FeFe] H(2)ases mimic catalyst 3, leading to the formation of the long-lived Fe(I)Fe(0) charge-separated state that can react with a proton to generate Fe(I)Fe(II).H, an intermediate for H(2) production. As a result, a reaction vessel for the photocatalytic H(2) production in an aqueous solution is established.

Total Synthesis of Bioactive Indolo[3,2-j]phenanthridine Alkaloid, Calothrixin B

The total synthesis of bioactive calothrixin B (2) was completed which two kinds of carbazoles using three approaches. The common strategy was based on an allene-mediated electrocyclic reaction of a 6π-electron system involving one or two indole [b]-bonds for the construction of an appropriate 4-oxygenated 2,3,4-trisubstituted carbazole 28 or a 6-oxygenated 5-methylindolo[2,3-a]carbazole 39, respectively. Oxidation of the methyl group of 28 followed by reduction of the nitro group of 21 afforded the pentacyclic phenol 5, which was oxidized with CAN to give calothrixin B (2). In a biomimetic pathway, the fully protected 5-formylindolo[2,3-a]carbazole 40 with a methoxymethyl group provided calothrixin B (2) through N-methoxymethyl-calothrixin B 43.

Iron‐Substituted Polyoxotungstates as Inorganic Synzymes: Evidence for a Biomimetic Pathway in the Catalytic Oxygenation of Catechols

Iron‐Substituted Polyoxotungstates as Inorganic Synzymes: Evidence for a Biomimetic Pathway in the Catalytic Oxygenation of Catechols

A Mild and Efficient Biomimetic Synthesis of Rodlike Hydroxyapatite Particles with a High Aspect Ratio Using Polyvinylpyrrolidone As Capping Agent

Rodlike hydroxyapatite (HAp) nanoparticles were synthesized at 60 °C through a biomimetic pathway from Ca(NO3)2·4H2O, H3PO4, and NH4OH. The polymer polyvinylpyrrolidone (PVP) as a capping agent was used to regulate the nucleation and crystal growth of HAp crystal. X-ray diffraction results combined with high-resolution transmission electron microscopy indicated that single phase, nanocrystal HAp powder could be obtained in one-step and the addition of PVP facilitated the preferential growth of nanocrystal HAp along the axis. The formation mechanism of rodlike HAp crystal and the effects of PVP on the crystal nucleation and growth were discussed based on transmission electron microscopy and Fourier transform infrared spectroscopy results.