- Construction of Janus dendrimers through a self-assembly approach involving chiral discrimination at a focal point
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A strategy to build Janus dendrimersviathe chirality-directed self-assembly of heteroleptic Zn(ii) BOX complexes is reported. The method allows quantitative synthesis of Janus dendrimersin situwithout the need for purifications. Each dendritic domain of t
- Zhou, John,Cole, Ashley M.,Menuey, Elizabeth M.,Kilway, Kathleen V.,Moteki, Shin A.
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supporting information
p. 6404 - 6407
(2021/07/02)
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- One-Component Multifunctional Sequence-Defined Ionizable Amphiphilic Janus Dendrimer Delivery Systems for mRNA
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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.
- Atochina-Vasserman, Elena N.,Billingsley, Margaret M.,Huang, Ning,Kim, Kyunghee,Liu, Matthew,Maurya, Devendra S.,Mitchell, Michael J.,Ni, Houping,Ona, Nathan,Percec, Virgil,Pochan, Darrin J.,Shahnawaz, Hamna,Weissman, Drew,Xiao, Qi,Zhang, Dapeng
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supporting information
p. 12315 - 12327
(2021/08/20)
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- Targeted Delivery of mRNA with One-Component Ionizable Amphiphilic Janus Dendrimers
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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.
- Zhang, Dapeng,Atochina-Vasserman, Elena N.,Maurya, Devendra S.,Liu, Matthew,Xiao, Qi,Lu, Juncheng,Lauri, George,Ona, Nathan,Reagan, Erin K.,Ni, Houping,Weissman, Drew,Percec, Virgil
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supporting information
p. 17975 - 17982
(2021/11/10)
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- Screening Libraries of Amphiphilic Janus Dendrimers Based on Natural Phenolic Acids to Discover Monodisperse Unilamellar Dendrimersomes
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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.
- Buzzacchera, Irene,Xiao, Qi,Han, Hong,Rahimi, Khosrow,Li, Shangda,Kostina, Nina Yu.,Toebes, B. Jelle,Wilner, Samantha E.,M?ller, Martin,Rodriguez-Emmenegger, Cesar,Baumgart, Tobias,Wilson, Daniela A.,Wilson, Christopher J.,Klein, Michael L.,Percec, Virgil
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p. 712 - 727
(2018/11/23)
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- Solvent clathrate driven dynamic stereomutation of a supramolecular polymer with molecular pockets
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Control over the helical organization of synthetic supramolecular systems is intensively pursued to manifest chirality in a wide range of applications ranging from electron spin filters to artificial enzymes. Typically, switching the helicity of supramole
- Kulkarni, Chidambar,Korevaar, Peter A.,Bejagam, Karteek K.,Palmans, Anja R.A.,Meijer,George, Subi J.
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supporting information
p. 13867 - 13875
(2017/11/07)
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- Micromolecular organogel factor, preparation method thereof and organogel
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The invention discloses a micromolecular organogel factor, a preparation method thereof and an organogel. The micromolecular organogel factor refers to N- (3,5-alkoxybenzoyl)-N-(4-cyanobenzoyl) hydrazine (the formula is shown as the specification), where
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Paragraph 0031
(2017/06/14)
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- Synthesis and characterization of bis [ n -(4-benzoyloxy) Benzylidene{ n (n -di-/tri-alkoxy)benzoyl}-hydrazinato]nickel(II) complexes displaying liquid crystalline columnar phases
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A series of materials based on the aroylhydrazinatonickel (II) complex is synthesized and characterized. The molecule in the materials consist of two 4-benzoyloxy-benzene groups and two benzene rings having two or three alkoxy chains containing 6, 8, 10,
- Abser, M. Nurul,Karim, M. Manzurul,Kauser, Abu,Parvin, Rabeya,Molla, M. Elias,Yeasmin, Zenifer,Zoghaib, Wajdi Michel,Al-Rawahi, Zainab,Carboni, Carlo,Al-Saidi, Ghalib
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- Synthesis and properties of 5,10,15,20-tetrakis[4-(3,5-dioctyloxybenzamido) phenyl]porphyrin and its metal complexes
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A novel 5,10,15,20-tetrakis[4-(3,5-dioctyloxybenzamido)phenyl]-porphyrin and its transition metal complexes are reported in this paper. Their molecular structures were characterized by elemental analysis as well as IR, 1H-NMR and UV-Vis spectroscopy. Their spectroscopic properties were studied by Raman and fluorescence spectroscopy, and X-ray photoelectron spectroscopy (XPS). The fluorescence quantum yields were measured at room temperature. The fluorescence intensity of the porphyrin ligand was stronger than the intensity of the complexes. There were large differences in the Raman spectrum of the porphyrin ligand and those of the metal complexes due to changes in the symmetry of porphyrin plane. In the XPS spectra, the replacement of the free-base protons by a metal ion to form the metalloporphyrin not only increases the symmetry of the molecule, but also introduces an electron withdrawing group into the center of the porphyrin ligand, which increases the N1S binding energy.
- Lian, Wenhui,Sun, Yuanyuan,Wang, Binbin,Shan, Ning,Shi, Tongshun
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experimental part
p. 335 - 348
(2012/05/20)
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- Synthesis of electron deficient acene derivatives via a bidirectional iterative elongation reaction
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Previously, we developed an iterative elongation methodology to synthesize acene esters, nitriles, and imides. The strategy uses the concept of bidirectional synthesis, and we can now make a series of electron deficient anthracene, tetracene, and pentacen
- Lin, Yi-Chun,Lin, Chih-Hsiu,Chen, Chan-Yu,Sun, Shih-Sheng,Pal, Bikash
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experimental part
p. 4507 - 4517
(2011/07/08)
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- Liquid crystalline behavior of tetraaryl derivatives of benzo[c]cinnoline, tetraazapyrene, phenanthrene, and pyrene: The effect of heteroatom and substitution pattern on phase stability
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A series of closely related tetrasubstituted derivatives of benzo[c]cinnoline (1), tetraazapyrene (2), phenanthrene (3), and pyrene (4) were investigated for their mesogenic properties using thermal, optical, spectroscopic, and powder XRD analyses. Only three 3,4-dioctyloxyphenyl derivatives exhibited mesogenic properties. Substitution of N for CH (3 → 1 and 4 → 2 pairs) and also increase of the core element size (1 → 2 and 3 → 4 pairs) significantly increases the mesophase stability. The findings and observed trends were rationalized by analysis of conformational properties which included calculation of the planarization energy, and modeling of aliphatic chain density and fill fractions. MO calculations showed that the tetraaza derivative 2c is significantly electron deficient and suitable for electron conductive materials. The Royal Society of Chemistry.
- Sienkowska, Monika J.,Farrar, John M.,Zhang, Fan,Kusuma, Sharat,Heiney, Paul A.,Kaszynski, Piotr
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p. 1399 - 1411
(2008/02/07)
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- Giant meso-meso-linked porphyrin arrays of micrometer molecular length and their fabrication
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On the basis of the AgI-promoted coupling reaction of zinc(II)-5,15-bis(3,5-dioctyloxyphenyl)porphyrin Z1, chain elongation has been attempted by using a stepwise doubling approach, which provides Z2, Z4, Z8, Z16, Z32, Z64, Z128, Z256, Z384, and Z512. The porphyrin arrays up to Z128 are sufficiently soluble in CHCl3 and THF despite their very long molecular lengths and rodlike structures, while the arrays over Z128 show a significant drop in solubility and stability. The discrete porphyrin arrays thus isolated were characterized by means of 1H NMR spectroscopy, matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry, UV/Vis spectroscopy, gel-permeation chromatography (GPC), cyclic voltammetry (CV), single-crystal X-ray crystallography, scanning tunneling microscopy (STM), and atomic force microscopy (AFM). Contrary to expected linear conformations of the arrays Z n (where n is the number of porphyrins), the single molecular images of Z128, Z256, and Z512 revealed largely bent structures; this finding indicates the substantial conformational flexibility of Zn. We also exploited an effective synthetic route by means of which Zn can be fabricated with a thiol-protected aryl group to provide ZnS2 through ZnBr2, by bromination with N-bromosuccinimide and subsequent Pd-catalyzed Suzuki-Miyaura arylation. Finally, the reaction of Z256 provided Z512, Z768, and Z1024. Collectively, this work provides an important milestone in the preparation of sub-microscale discrete organic molecules and the fabrication of molecular-based materials, hence significantly contributing to device applications.
- Aratani, Naoki,Takagi, Akihiko,Yanagawa, Yoshiki,Matsumoto, Takuya,Kawai, Tomoji,Yoon, Zin Seok,Kim, Dongho,Osuka, Atsuhiro
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p. 3389 - 3404
(2007/10/03)
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- Tuning organogels and mesophases will phenanthroline ligands and their copper complexes by inter- to intramolecular hydrogen bonds
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A novel family of highly functionalized molecules consisting of a central 4-methyl-3,5-diacylaminobenzene platform linked in close proximity to the methyl group by two lateral aromatic rings each equipped with two long alkoxy chains has been rationally de
- Ziessel, Raymond,Pickaert, Guillaume,Camerel, Franck,Donnio, Bertrand,Guillon, Daniel,Cesario, Michele,Prange, Thierry
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p. 12403 - 12413
(2007/10/03)
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- Synthesis of oligopyridinic scaffolds from amido substituted phenyl rings for extended hydrogen bonding
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A series of phenanthroline, terpyridine and pyridino-oxazoline ligands combining a 4-methyl-3,5-diacylaminophenyl platform and two dialkoxyphenyl groups has been prepared by a linear multistep protocol. The synthetic potential of 4-methyl-3,5-(diacyl-amin
- Pickaert, Guillaume,Ziessel, Raymond
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p. 2716 - 2726
(2007/10/03)
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- Dendritic TADDOLs: Synthesis, characterization and use in the catalytic enantioselective addition of Et2Zn to benzaldehyde
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The versatile chiral ligand for polar metal centers, TADDOL ((R,R)-a,a,a′,a′-tetraaryl-1,3-dioxolane-4,5-dimethanol), has been incorporated as core building block into dendrimers by way of benzylation of a fourfold phenolic derivative (hexol 2) with Frech
- Rheiner, P. Beat,Seebach, Dieter
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p. 3221 - 3236
(2007/10/03)
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