863591-43-9

Upstream product

• 18908-66-2 3-bromomethylheptane 
• 2150-44-9 1-carbomethoxy-3,5-dihydroxybenzene 
• 99-10-5 3,5-Dihydroxybenzoic acid 

Downstream Products

• 863591-45-1 (3,5-bis((2-ethylhexyl)oxy)phenyl)methanol 
• 1119826-13-9 1,2-bis[3,5-di(2-ethylhexyloxy)phenyl]ethanedione 
• 1119084-42-2 3,5-bis((2-ethylhexyl)oxy)benzoic acid 
• 1442742-08-6 2,2-bis(azidomethyl)propane-1,3-diyl bis(3,5-bis((2-ethyloctyl)oxy)benzoate) 
• 1147710-40-4 2-(3,5-bis((2-ethylhexyl)oxy)benzyl)isoindoline-1,3-dione 
• 1147710-41-5 1-(aminomethyl)-3,5-di(2-ethylhexyloxy)benzene 

Relevant academic research and scientific papers

One-Component Multifunctional Sequence-Defined Ionizable Amphiphilic Janus Dendrimer Delivery Systems for mRNA

Efficient viral or nonviral delivery of nucleic acids is the key step of genetic nanomedicine. Both viral and synthetic vectors have been successfully employed for genetic delivery with recent examples being DNA, adenoviral, and mRNA-based Covid-19 vaccines. Viral vectors can be target specific and very efficient but can also mediate severe immune response, cell toxicity, and mutations. Four-component lipid nanoparticles (LNPs) containing ionizable lipids, phospholipids, cholesterol for mechanical properties, and PEG-conjugated lipid for stability represent the current leading nonviral vectors for mRNA. However, the segregation of the neutral ionizable lipid as droplets in the core of the LNP, the "PEG dilemma", and the stability at only very low temperatures limit their efficiency. Here, we report the development of a one-component multifunctional ionizable amphiphilic Janus dendrimer (IAJD) delivery system for mRNA that exhibits high activity at a low concentration of ionizable amines organized in a sequence-defined arrangement. Six libraries containing 54 sequence-defined IAJDs were synthesized by an accelerated modular-orthogonal methodology and coassembled with mRNA into dendrimersome nanoparticles (DNPs) by a simple injection method rather than by the complex microfluidic technology often used for LNPs. Forty four (81%) showed activity in vitro and 31 (57%) in vivo. Some, exhibiting organ specificity, are stable at 5 °C and demonstrated higher transfection efficiency than positive control experiments in vitro and in vivo. Aside from practical applications, this proof of concept will help elucidate the mechanisms of packaging and release of mRNA from DNPs as a function of ionizable amine concentration, their sequence, and constitutional isomerism of IAJDs.

Targeted Delivery of mRNA with One-Component Ionizable Amphiphilic Janus Dendrimers

Targeted and efficient delivery of nucleic acids with viral and synthetic vectors is the key step of genetic nanomedicine. The four-component lipid nanoparticle synthetic delivery systems consisting of ionizable lipids, phospholipids, cholesterol, and a PEG-conjugated lipid, assembled by microfluidic or T-tube technology, have been extraordinarily successful for delivery of mRNA to provide Covid-19 vaccines. Recently, we reported a one-component multifunctional sequence-defined ionizable amphiphilic Janus dendrimer (IAJD) synthetic delivery system for mRNA relying on amphiphilic Janus dendrimers and glycodendrimers developed in our laboratory. Amphiphilic Janus dendrimers consist of functional hydrophilic dendrons conjugated to hydrophobic dendrons. Co-assembly of IAJDs with mRNA into dendrimersome nanoparticles (DNPs) occurs by simple injection in acetate buffer, rather than by microfluidic devices, and provides a very efficient system for delivery of mRNA to lung. Here we report the replacement of most of the hydrophilic fragment of the dendron from IAJDs, maintaining only its ionizable amine, while changing its interconnecting group to the hydrophobic dendron from amide to ester. The resulting IAJDs demonstrated that protonated ionizable amines play dual roles of hydrophilic fragment and binding ligand for mRNA, changing delivery from lung to spleen and/or liver. Replacing the interconnecting ester with the amide switched the delivery back to lung. Delivery predominantly to liver is favored by pairs of odd and even alkyl groups in the hydrophobic dendron. This simple structural change transformed the targeted delivery of mRNA mediated with IAJDs, from lung to liver and spleen, and expands the utility of DNPs from therapeutics to vaccines.

Screening Libraries of Amphiphilic Janus Dendrimers Based on Natural Phenolic Acids to Discover Monodisperse Unilamellar Dendrimersomes

Natural, including plant, and synthetic phenolic acids are employed as building blocks for the synthesis of constitutional isomeric libraries of self-assembling dendrons and dendrimers that are the simplest examples of programmed synthetic macromolecules.

MODULAR SYNTHESIS OF AMPHIPHILIC JANUS GLYCODENDRIMERS AND THEIR SELF-ASSEMBLY INTO GLYCODENDRIMERSOMES

The invention concerns compounds of the formula (I) wherein: Y1 and Y2 are independently a monosaccharide or disaccharide; X1 and X2 are independently -(R9-O)m-, -(R10)P-, -O-(R11-O)q-, -R16-O-R17-O- or a covalent bond; Q1 and Q2 are independently a nitrogen-containing heterocycle moiety; Z1 and Z2 are independently -(O-R7)-, -(O-C(=O)-R8)a-, -O-C(=O)-R12-C(=0)-R13-, -O- C(=O)-R14-C(=O)-R15 or a covalent bond; R7-R17 are each independently C1-C6 alkyl; R1-R6 are each independently a linear or branched alkly group; b, c, d, e, f, and g are 0 or 1, provided b + c + d equals at least 2 and e + f + g equals at least 2; and a, m, p, and q are each an integer from 1-6.

Modular synthesis of amphiphilic Janus glycodendrimers and their self-assembly into glycodendrimersomes and other complex architectures with bioactivity to biomedically relevant lectins

The modular synthesis of 7 libraries containing 51 self-assembling amphiphilic Janus dendrimers with the monosaccharides d-mannose and d-galactose and the disaccharide d-lactose in their hydrophilic part is reported. These unprecedented sugar-containing dendrimers are named amphiphilic Janus glycodendrimers. Their self-assembly by simple injection of THF or ethanol solution into water or buffer and by hydration was analyzed by a combination of methods including dynamic light scattering, confocal microscopy, cryogenic transmission electron microscopy, Fourier transform analysis, and micropipet-aspiration experiments to assess mechanical properties. These libraries revealed a diversity of hard and soft assemblies, including unilamellar spherical, polygonal, and tubular vesicles denoted glycodendrimersomes, aggregates of Janus glycodendrimers and rodlike micelles named glycodendrimer aggregates and glycodendrimermicelles, cubosomes denoted glycodendrimercubosomes, and solid lamellae. These assemblies are stable over time in water and in buffer, exhibit narrow molecular-weight distribution, and display dimensions that are programmable by the concentration of the solution from which they are injected. This study elaborated the molecular principles leading to single-type soft glycodendrimersomes assembled from amphiphilic Janus glycodendrimers. The multivalency of glycodendrimersomes with different sizes and their ligand bioactivity were demonstrated by selective agglutination with a diversity of sugar-binding protein receptors such as the plant lectins concanavalin A and the highly toxic mistletoe Viscum album L. agglutinin, the bacterial lectin PA-IL from Pseudomonas aeruginosa, and, of special biomedical relevance, human adhesion/growth-regulatory galectin-3 and galectin-4. These results demonstrated the candidacy of glycodendrimersomes as new mimics of biological membranes with programmable glycan ligand presentations, as supramolecular lectin blockers, vaccines, and targeted delivery devices.

The synthesis of symmetric and asymmetric perylene derivatives and their optical properties

Symmetric bisimidazole and asymmetric imide-imidazole derivatives having a perylene structure were synthesized. Long, hyperbranched alkyl groups, attached to the benzimidazole moeity, enhanced the solubility of the imidazole derivatives. Soluble asymmetric imide-imidazoles were prepared using 1,2-diaminophenyls which contained methoxy, nitro and ester groups. The effects of both electron-withdrawing and donating groups were examined optically and electronically using both absorption and emission spectroscopy. Photoluminescence spectroscopy revealed that the various perylene derivatives displayed varying quantum yield; frontier orbital energy levels were determined using cyclic voltammetric analysis. The asymmetric imide-imidazole displayed the transient, electronic and optical properties of symmetric bisimide and symmetric bisimidazole perylene derivatives. Nitro derivation reduced the LUMO energy level of the asymmetric perylene by 0.05?eV while methoxy derivation increased it by 0.07?eV, in comparison with that of the unsubstituted, asymmetric perylene. Either bathochromic or hypsochromic spectral shifts of the asymmetric imidazoles were observed in solid film, depending on electronic substituent.

Photovoltaic performance of an ultrasmall band gap polymer

A conjugated polymer (PBTTQ) that consists of alternating electron-rich bithiophene and electron-deficient thiadiazoloquinoxaline units was synthesized via Yamamoto polymerization with Ni(cod)2 and provides a band gap of 0.94 eV. This represents one of the smallest band gaps obtained for a soluble conjugated polymer. When applied in a bulk heterojunction solar cell together with [84]PCBM as the electron acceptor, the polymer affords a response up to 1.3μm.

A new approach toward light-harvesting reverse micelles from donor-acceptor miscible blends

In the present paper, we report a new approach toward light-harvesting reverse micellar systems from molecular blends of anthracene and perylene building blocks. The self-assembly initiated by protonation of the molecular blends gave rise to the mixed rev