Clotting Blood into an Adhesive Gel by Hemostatic Powder Based on Cationic/Anionic Polysaccharides and Laponite.

Hemostatic powder is widely employed for emergency bleeding control due to its ability to conform to irregularly shaped wounds, ease of use, and stable storage. However, current powders exhibit limited tissue adhesion and insufficient support for thrombus formation, making them easily washed away by blood. In this study, a hybrid powder (QAL) was produced by mixing quaternized chitosan (QCS) powder, catechol-modified alginate (Cat-SA) powder, and laponite (Lap) powder. Upon addition of QAL, the blood quickly transformed to a robust and adhesive blood gel. The adhesion strength of the blood gel was up to 31.33 ± 1.56 kPa. When compared with Celox, QAL showed superior performance in promoting hemostasis. Additionally, QAL exhibited effectiveness in eliminating bacteria while also demonstrating outstanding biocompatibility with cells and blood. These favorable properties, including strong coagulation, adhesion to wet tissue, antibacterial activity, biosafety, ease of use, and stable storage, make QAL a promising emergency hemostatic agent.

Bischler-Napieralski Synthesis of Polycyclic N-Heteroaromatics Based on Tf2O-Promoted Electrophilic Activation of N-Aryl-2-Propynamides.

2-Propynamides have been never used as substrates in classic and Tf2O-promoted Bischler-Napieralski reactions. In this article, a novel tandem synthesis of benzo[a]acridines is developed from N-aryl-2-propynamides and alkynes consisting of a Tf2O-promoted intermolecular Bischler-Napieralski reaction and a TfOH-promoted intramolecular Friedel-Crafts reaction.

Bischler-Napieralski Synthesis of 6-Alkynyl Phenanthridines Based on Tf2O-Promoted Electrophilic Activation of N-Aryl-2-propynamides.

An efficient method for the synthesis of 6-alkynyl phenanthridines was developed. The method offered the first example to use 2-propynamides as substrates in the Bischler-Napieralski reaction and to create alkynylnitrilium triflates as new active intermediates in organic synthesis.

Tandem Synthesis of 1,3-Disubstituted Naphthalenes via TfOH-Promoted Directed-Aldol and Friedel-Crafts Reactions.

A TfOH-promoted tandem synthesis of 1,3-disubstituted naphthalenes is developed via a directed-aldol reaction and a Friedel-Crafts reaction. Two new C-C bonds and one new benzene ring are created efficiently in one pot due to the discovery of a TfOH-promoted highly chemoselective directed-aldol reaction between two different ketones with α-hydrogens.

General Synthesis of Fully Substituted 4-Aminooxazoles from Amides and 1,4,2-Dioxazol-5-ones Based on Amide Activation and Umpolung Process.

A general and efficient synthesis of fully substituted 4-aminodixazoles was developed based on the strategies of amide activation and umpolung reaction. In this method, 1,4,2-dioxazol-5-ones were introduced as a rare type of umpolung reagent bearing a nucleophilic N-atom that could be used well together with the activating agent Tf2O. Because 1,4,2-dioxazol-5-ones played triple roles as an umpolung reagent, a substrate, and a weak base, the method proceeded smoothly under extremely convenient conditions.

Metal-Free Method for Direct Synthesis of Functionalized ß-Ketoenamines.

A new method for direct synthesis of ß-ketoenamines was developed by a BF3·OEt2-catalyzed cyclization of 1-iodoalkyne and α-keto acid followed by an amine-mediated ring-opening in one pot. Its metal-free conditions allowed the easy synthesis of those products bearing the transition metal-sensitive functional groups. Its three-component process achieved wide range of functionalized products.

Carboxy Group as a Remote and Selective Chelating Group for C-H Activation of Arenes.

The first example of carboxy group assisted, remote-selective C(sp2 )-H activation with a PdII catalyst has been developed and proceeds through a possible κ2 coordination of the carboxy group, thus suppressing the ortho-C-H activation through κ1 coordination. Besides meta-C-H olefination, direct meta-arylation of hydrocinnamic acid derivatives with low-cost aryl iodides has been achieved for the first time. These findings may motivate the exploration of novel reactivities of the carboxy assisted C-H activation reactions with intriguing selectivities.

Synthesis of 2-Aminopyridines via a Base-Promoted Cascade Reaction of N-Propargylic ß-Enaminones with Formamides.

N-Substituted formamides as nucleophiles react with in situ-generated 1,4-oxazepines from N-propargylic ß-enaminones followed by spontaneous N-deformylation to deliver densely substituted 2-aminopyridines in good yields (31-88%). The formyl group is found to be a superior traceless activating group of free amines and would ultimately be removed in situ. This reaction proceeds smoothly at room temperature, in the presence of NaOH as sole additive, without protection from the atmosphere and generates H2O and sodium formate as byproducts.

Transition-Metal-Free Cascade Approach toward 2-Alkoxy/2-Sulfenylpyridines and Dihydrofuro[2,3-b]pyridines by Trapping In Situ Generated 1,4-Oxazepine.

An efficient cascade reaction via trapping in situ generated active intermediate 1,4-oxazepine, formed from base-promoted 7-exo-dig cyclization reaction of N-propargyl enaminone, has been developed. Alcohols/thiols and aldehydes were used as trapping agents, providing 2-alkoxy/2-sulfenylpyridines and dihydrofuro[2,3-b]pyridines in moderate to high yields. This cascade reaction was completed within 30 min at room temperature, generating 1 equiv of H2O as the sole byproduct.

Access to Indole Derivatives from Diaryliodonium Salts and 2-Alkynylanilines.

An efficient, environmentally friendly, and operationally simple procedure to 1,2-disubstituted indoles from 2-alkynylanilines and diaryliodonium salts has been developed. This reaction proceeds smoothly under metal-free conditions. The products obtained could be transferred into 3,3'-diindolylmethane with DMSO catalyzed by palladium. The isotopic label experiments indicated that the methylene group in 3,3'-diindolylmethane is derived from DMSO. The diverse indoles were obtained in up to 90% yield for 28 examples.

Gluing blood into adhesive gel by oppositely charged polysaccharide dry powder inspired by fibrin fibers coagulation mediator.

Hemostatic powders that adapt to irregularly shaped wounds, allowing for easy application and stable storage, have gained popularity for first-aid hemorrhage control. However, traditional powders often provide weak thrombus support and exhibit limited tissue adhesion, making them susceptible to dislodgment by the bloodstream. Inspired by fibrin fibers coagulation mediator, we have developed a bi-component hemostatic powder composed of positively charged quaternized chitosan (QCS) and negatively charged catechol-modified alginate (Cat-SA). Upon application to the wound, the bi-component powders (QCS/Cat-SA) rapidly absorb plasma and dissolve into chains. These chains interact with each other to form a network, which can effectively bind and entraps clustered red blood cells and platelets, ultimately leading to the creation of a durable and robust thrombus. Significantly, these interconnected polymers adhere to the injury site, offering protection against thrombus disruption caused by the bloodstream. Benefiting from these synthetic properties, QCS/Cat-SA demonstrates superior hemostatic performance compared to commercial hemostatic powders like Celox™ in both arterial injuries and non-compressible liver puncture wounds. Importantly, QCS/Cat-SA exhibits excellent antibacterial activity, cytocompatibility, and hemocompatibility. These advantages of QCS/Cat-SA, including strong blood clotting, wet tissue adherence, antibacterial activity, biosafety, ease of use, and stable storage, make it a promising hemostatic agent for emergency situations.

Cohering Plasma into Adhesive Gel by Natural Biopolymer-Nanoparticle Hybrid Powder for Efficient Hemostasis and Wound Healing.

Hemostatic powder is commonly used in emergency bleeding control due to its suitability for irregularly shaped wounds, ease of use, and stable storage. However, traditional powder often has limited tissue adhesion and weak thrombus support, which makes it vulnerable to displacement by blood flow. Herein, we have developed a tricomponent hemostatic powder (MQS) composed of mesoporous bioactive glass nanoparticle (MBG), positively charged quaternized chitosan (QCS), and negatively charged catechol-modified alginate (SADA). Upon application to the wound, MBG with its high specific surface area quickly absorbs plasma, concentrating the blood coagulation factor. Simultaneously, the water-soluble QCS and SADA interact with each other and form a net, which can be further cross-linked by MBG. This network efficiently binds and entraps clustered blood coagulation factors, ultimately resulting in the formation of a durable and robust thrombus. Furthermore, the formed net adheres to the injury site, offering protection against thrombus disruption caused by the bloodstream. Benefiting from the synergistic effect of these three components, MQS demonstrates superior hemostatic performance compared to commercial hemostatic powders like Celox in both arterial injuries and noncompressible liver puncture wounds. Furthermore, MQS can effectively accelerate wound healing. In addition, MQS exhibits excellent antibacterial activity, cytocompatibility, and hemocompatibility. These advantages of MQS, including strong blood clotting, wet tissue adherence, antibacterial activity, wound healing ability, biosafety, ease of use, and stable storage, make it a promising hemostatic agent for emergency situations.

Ferried Albumin-Inspired Bioadhesive With Dynamic Interfacial Bonds for Emergency Rescue.

Emergency prehospital wound closure and hemorrhage control are the first priorities for life-saving. Majority of bioadhesives form bonds with tissues through irreversible cross-linking, and the remobilization of misalignment may cause severe secondary damage to tissues. Therefore, developing an adhesive that can quickly and tolerably adhere to traumatized dynamic tissue or organ surfaces in emergency situations is a major challenge. Inspired by the structure of human serum albumin (HSA), a branched polymer with multitentacled sulfhydryl is synthesized, then, an instant and fault-tolerant tough wet-tissue adhesion (IFA) hydrogel is prepared. Adhesive application time is just 5 s (interfacial toughness of ≈580 J m-2), and favorable tissue-adhesion is maintained after ten cycles. IFA hydrogel shows unchangeable adhesive performance after 1 month of storage based on the internal oxidation-reduction mechanism. It not only can efficiently seal various organs but also achieves effective hemostasis in models of the rat femoral artery and rabbit-ear artery. This work also proposes an effective strategy for controllable adhesion, enabling the production of asymmetric adhesives with on-demand detachment. Importantly, IFA hydrogel has sound antioxidation, antibacterial property, hemocompatibility, and cytocompatibility. Hence, the HSA-inspired bioadhesive emerges as a promising first-aid supply for human-machine interface-based health management and non-invasive wound closure.

Coagulating blood into adhesive gel by hybrid powder based on oppositely charged polysaccharide/tannic acid-modified mesoporous bioactive glass.

Hemostatic powder is widely utilized in emergency situations to control bleeding due to its ability to work well on wounds with irregular shapes, ease of application, and long-term stability. However, traditional powder often suffers from limited tissue adhesion and insufficient support for blood clot formation, leaving it susceptible to displacement by the flow of blood. This study introduces a hemostatic powder composed of tannic modified mesoporous bioactive glass (TMBG), cationic quaternized chitosan (QCS), and anionic hyaluronic acid modified with catechol group (HADA). The resulting TMBG/QCS/HADA based hemostatic powder (TMQH) rapidly absorbs plasma, concentrating blood coagulation factors. Simultaneously, the water-soluble QCS and HADA interact to form a 3D network structure, which can be strengthened by crosslinking with TMBG. This network effectively captures clustered blood coagulation factors, leading to a strong and adhesive thrombus that resists disruption from blood flow. TMQH exhibits superior efficacy in promoting hemostasis compared to Celox™ both in rat arterial injuries and non-compressible liver puncture wounds. TMQH demonstrates excellent antibacterial activity, cytocompatibility, and blood compatibility. These outstanding superiorities in blood clotting capability, wet tissue adhesion, antibacterial activity, safety for living organisms, ease of application, and long-term stability, make TMQH highly suitable for emergency hemostasis.

Mussel Foot Protein-Inspired Adhesive Tapes with Tunable Underwater Adhesion.

Instant and strong adhesion to underwater adherends is a big challenge due to the continuous interference of water. Mussel foot protein-bioinspired catechol-based adhesives have garnered great interest in addressing this issue. Herein, a novel self-made catecholic compound with a long aliphatic chain was utilized to prepare thin (∼0.07 mm) and optically transparent (>80%) wet/underwater adhesive tapes by UV-initiated polymerization. Its adhesion activity was water-triggered, fast (<1 min), and strong (adhesion strength to porcine skin: ∼1.99 MPa; interfacial toughness: ∼610 J/m2, burst pressure: ∼1950 mmHg). The effect of the catechol/phenol group and positively charged moiety on the wet/underwater adhesion to abiotic/biotic substrates was investigated. On the wet/underwater adherends, the tape with catechol groups presented much higher interfacial toughness, adhesion strength, and burst pressure than the analogous tape with phenol groups. The tape with both the catechol group and cationic polyelectrolyte chitosan had a more impressive improvement in its adhesion to wet/underwater biological tissues than to abiotic substrates. Therefore, catechol and a positive moiety in the tape would synergistically enhance its wet/underwater adhesion to various substrates, especially to biological tissues. The instant, strong, and noncytotoxic tape may provide applications in underwater adhesion for sealing and wound closure.

Amphiphilic Janus cotton gauze with enhanced moisture management and blood coagulation for rapid hemostasis and wound healing.

Cotton gauze is commonly used in initial emergency care. However, its high hydrophilicity and limited clotting capacity can lead to the excessive absorption of blood, resulting in unnecessary blood loss. Herein, an amphiphilic Janus cotton gauze with excellent moisture management and enhanced blood coagulation has been developed via in situ generating bioactive glass (BG) onto the cotton gauze (CG), and then attaching cardanol (CA) onto one side of the BG-loaded CG (CG@BG) via click reaction. The Janus gauze (CA-CG@BG) has asymmetric wetting properties with a hydrophilic side (CA-CG@BGHL) and a hydrophobic side (HBCA-CG@BG). When applied to hemostatic, the porous and active BG on CA-CG@BGHL can rapidly initiate coagulation cascade to form a robust thrombus. CA on HBCA-CG@BG can entangled with each other, creating a hydrophobic barrier that prevents blood from flowing out. The hemostatic performance of CA-CG@BG is superior to that of CG in both rats and pigs. Interestingly, CA-CG@BG possesses unidirectional exudate removal. When applied to wound healing, the exudate can penetrate the hydrophobic HBCA-CG@BG to the hydrophilic CA-CG@BGHL, resulting in faster wound healing than CG. CA-CG@BG exhibits excellent cytocompatibility and hemocompatibility. This unique Janus dressing shows promise as a potential material for clinical applications in the future.

Polysaccharides based rapid self-crosslinking and wet tissue adhesive hemostatic powders for effective hemostasis.

Hemostatic powders with flexible shape are widely used for the noncompressible and inaccessible hemorrhage wounds. However, current hemostatic powders display poor wet tissue adhesion and fragile mechanical strength of the powder-supported blood clots, leading to compromised hemostasis efficacy. Herein, a bi-component of carboxymethyl chitosan (CMCS) and aldehyde-modified hyaluronic acid grafted with catechol groups (COHA) was designed. Upon absorption of blood, the bi-component powders (CMCS-COHA) spontaneously self-crosslinks into an adhesive hydrogel within 10 s, tightly adhering to wound tissue to form a pressure-resistant physical barrier. During gelation, the hydrogel matrix captures and locks the blood cells/platelets to generate a robust thrombus in the bleeding sites. Compared with traditional hemostatic powder Celox™, CMCS-COHA displays superior blood coagulation and hemostatic performance. More importantly, CMCS-COHA has inherent cytocompatibility and hemocompatibility. These prominent advantages in rapid and effective hemostasis, adaptability to fit irregulate defective wound, easy preservation, facile usage, and bio-safety, make CMCS-COHA a promising hemostatic in emergency situations.

Mussel Foot Protein Inspired Tape-Type Adhesive with Water-Responsive, High Conformal, Tough, and On-Demand Detachable Adhesion to Wet Tissue.

Wet adhesion is highly demanded in noninvasive wound closure, tissue repair, and biomedical devices, but it is still a big challenge for developing biosafe and tough wet bioadhesives due to low or even nonadhesion in the wet state for conventional adhesives. Inspired by the wet-adhesion-contributing factors of mussel foot proteins, a water-responsive dry robust tissue adhesive PAGU tape is made with thickness of <0.5 mm through fast UV-initiated copolymerization of acrylic acid (AA), gelatin (Gel), and hexadecenyl-1,2-catechol (UH). The tape shows strong cohesive mechanical properties and strong interfacial adhesion bonds. Upon application onto wet tissue, the adhesive tape can conform to the tissue, quickly dry tissue surface through absorbing surface/interfacial water and then allows formation of interfacial bonding with a high interfacial toughness of ≈818 J m-2 . Furthermore, it can be readily detached by treating with aq. urea solution. A highly efficient avenue is provided here for producing conformable, tough, and easy detachable wet bioadhesive tapes.

Robust but On-Demand Detachable Wet Tissue Adhesive Hydrogel Enhanced with Modified Tannic Acid.

Adhesives with robust but readily detachable wet tissue adhesion are of great significance for wound closure. Polyelectrolyte complex adhesive (PECA) is an important wet tissue adhesive. However, its relatively weak cohesive and adhesive strength cannot satisfy clinical applications. Herein, modified tannic acid (mTA) with a catechol group, a long alkyl hydrophobic chain, and a phenyl group was prepared first, and then, it was mixed with acrylic acid (AA) and polyethylenimine (PEI), followed by UV photopolymerization to make a wet tissue adhesive hydrogel with tough cohesion and adhesion strength. The hydrogel has a strong wet tissue interfacial toughness of ∼1552 J/m2, good mechanical properties (∼7220 kPa cohesive strength, ∼873% strain, and ∼33,370 kJ/m3 toughness), and a bursting pressure of ∼1575 mmHg on wet porcine skin. The hydrogel can realize quick and effective adhesion to various wet biological tissues including porcine skin, liver, kidney, and heart and can be changed easily with triggering urea solution to avoid tissue damage or uncomfortable pain to the patient. This biosafe adhesive hydrogel is very promising for wound closure and may provide new ideas for the design of robust wet tissue adhesives.

Tough and On-Demand Detachable Wet Tissue Adhesive Hydrogel Made from Catechol Derivatives with a Long Aliphatic Side Chain.

Wet adhesion is critical in cases of wound closure, but it is usually deterred by the hydration layer on tissues. Inspired by dopamine-mediated underwater adhesion in mussel foot proteins, wet tissue adhesives containing catechol with 2-3 carbons side chains are reported mostly. To make wet adhesion of this type of adhesives much tougher, catechol derivatives with a long aliphatic side chain (≈10 atoms length) are synthesized. Then, a series of strong wet tissue adhesive hydrogels are prepared through photoinduced copolymerization of acrylic acid with synthetic monomers. The adhesive hydrogel has a high cohesion strength, that is, tensile strength and strain, and toughness of ≈1800 kPa, ≈540%, and ≈4100 kJ m-3 , respectively. Its interfacial toughness on wet and underwater porcine skin is respectively ≈1300 and ≈1100 J m-2 , and its adhesion strength to wet porcine skin is ≈153 kPa. These values are much higher than those of dopamine-based adhesives in the same conditions, demonstrating that the long aliphatic side chain on catechol can greatly improve the wet tissue-adhesion. Additionally, the tough interfacial adhesion can be broken on demand with 5 wt.% aqueous urea solution. This adhesive hydrogel is highly promising in safe wound closure.