- Design, synthesis, and transfection biology of novel cationic glycolipids for use in liposomal gene delivery
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The molecular structure of the cationic lipids used in gene transfection strongly influences their transfection efficiency. High transfection efficiencies of non-glycerol-based simple monocationic transfection lipids with hydroxyethyl headgroups recently reported by us (Banerjee et al. J. Med. Chem. 1999, 42, 4292-4299) are consistent with the earlier observations that the presence of hydroxyl functionalities in the headgroup region of a cationic lipid contributes favorably in liposomal gene delivery. Using simple sugar molecules as the source of multiple hydroxyl functionalities in the headgroup region of the transfection lipids, we have synthesized four novel simple monocationic transfection lipids, namely, 1-deoxy-1-[dihexadecyl(methyl)-ammonio]-D-xylitol (1), 1-deoxy-1-[methyl(ditetradecyl)ammonio]-D-arabinitol (2), 1-deoxy-1-[dihexadecyl(methyl)ammonio]-D-arabinitol (3) and 1-deoxy-1-[methyl(dioctadecyl)ammonio]-D-arabinitol (4), containing hydrophobic aliphatic tails and the hydrophilic arabinosyl or xylose sugar groups linked directly to the positively charged nitrogen atom. Syntheses, chemical characterizations, and the transfection biology of these novel transfection lipids 1-4 are described in this paper. Lipid 1, the xylosyl derivative, showed maximum transfection on COS-1 cells. All the lipids showed transfection with cholesterol as colipid and not with dioleoylphosphatidylethanolamine (DOPE). Radioactive quantitation of free and complexed DNA combined with ethidium bromide exclusion measurements suggest that though nearly 70% of the DNA exists as complexed DNA, the DNA may not have condensed as was observed with other cationic lipids. Presence of additional (more than two) hydroxyl functionalities in the headgroup of the cationic lipids appears to have improved the transfection efficiency and made these lipids less cytotoxic compared to two-hydroxyl derivatives.
- Banerjee,Mahidhar,Chaudhuri,Gopal,Rao
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- Molecular recognition of nucleotides by the guanidinium unit at the surface of aqueous micelles and bilayers. A comparison of microscopic and macroscopic interfaces
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Molecular recognition of the guanidinium/phosphate pair was investigated at microscopic interfaces of aqueous micelles and bilayers. Monoalkyl and dialkyl amphiphiles with guanidinium head groups were synthesized and dispersed in water to form micelles and bilayers having guanidinium groups at the aggregate surface. Binding of nucleotides such as AMP to these functionalized aggregates was evaluated by using an equilibrium dialysis (ultrafiltration) method. The observed binding constants of 102-104 M-1 are much larger than the corresponding binding constant reported for a monomerically dispersed pair in the aqueous phase (1.4 M-1) but are smaller than those found at the macroscopic air-water interface (106-107 M-1). Therefore, the macroscopic interface promotes guanidinium-phosphate interaction more effectively than the microscopic interface. The present finding indicates that the microscopic interface can strengthen hydrogen bonding and/or electrostatic interaction even in the presence of water. Saturation binding phenomena were different between micelles and bilayers. All of the guanidinium groups in fluid micelles are effective for phosphate binding, but part of the guanidinium group in bilayers are not effective probably because of steric restriction.
- Onda,Yoshihara,Koyano,Ariga,Kunitake
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- Selective Transformations of Triglycerides into Fatty Amines, Amides, and Nitriles by using Heterogeneous Catalysis
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The use of triglycerides as an important class of biomass is an effective strategy to realize a more sustainable society. Herein, three heterogeneous catalytic methods are reported for the selective one-pot transformation of triglycerides into value-added chemicals: i) the reductive amination of triglycerides into fatty amines with aqueous NH3 under H2 promoted by ZrO2-supported Pt clusters; ii) the amidation of triglycerides under gaseous NH3 catalyzed by high-silica H-beta (Hβ) zeolite at 180 °C; iii) the Hβ-promoted synthesis of nitriles from triglycerides and gaseous NH3 at 220 °C. These methods are widely applicable to the transformation of various triglycerides (C4–C18 skeletons) into the corresponding amines, amides, and nitriles.
- Jamil, Md. A. R.,Siddiki, S. M. A. Hakim,Touchy, Abeda Sultana,Rashed, Md. Nurnobi,Poly, Sharmin Sultana,Jing, Yuan,Ting, Kah Wei,Toyao, Takashi,Maeno, Zen,Shimizu, Ken-ichi
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p. 3115 - 3125
(2019/04/26)
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- Conversion of Primary Amines to Symmetrical Secondary and Tertiary Amines using a Co-Rh Heterobimetallic Nanocatalyst
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Symmetrical tertiary amines have been efficiently realized from amine and secondary amines via deaminated homocoupling with heterogeneous bimetallic Co2Rh2/C as catalyst (molar ratio Co:Rh=2:2). Unsymmetric secondary anilines were produced from the reaction of anilines with symmetric tertiary amines. The Co2Rh2/C catalyst exhibited very high catalytic activity towards a wide range of amines and could be conveniently recycled ten times without considerable leaching. (Figure presented.).
- Chung, Hyunho,Han, Seulgi,Chung, Young Keun,Park, Ji Hoon
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supporting information
p. 1267 - 1272
(2018/02/12)
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- Scaling the effect of hydrophobic chain length on gene transfer properties of di-alkyl, di-hydroxy ethylammonium chloride based cationic amphiphiles
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The success of gene therapy critically depends on the availability of efficient transfection vectors. Cationic lipids are the most widely studied non-viral vectors. The molecular architecture of the cationic lipid determines its transfection efficiency. Variations in alkyl chain lengths of lipids influence self-assembly and liposomal fusion with the cell membrane. These factors determine the transfection ability of the lipid. Thus, to probe the effect of asymmetry in hydrophobic chains on transfection efficiency, we designed and synthesized a series of cationic lipids by systematically varying one of the two alkyl chains linked to the quaternary nitrogen centre from C18 to C10 and keeping the other alkyl C18 chain constant (Lip1818-Lip1810). Transfection studies in multiple cultured mammalian cells (CHO, B16F10 and HeLa) revealed that the lipids with C18:C14 and C18:C12 alkyl chains (Lip1814 & Lip1812) showed 20-30% higher transfection efficacies than their counterparts at 2:1 and 4:1 lipid to pDNA charge ratios. Cryo-transmission electron images showed unilamellar vesicle structures for the liposomes of lipids. Mechanistic studies involving Small Angle X-ray Scattering (SAXS) revealed that asymmetry in the hydrophobic region has a significant impact on liposomal fusion with the plasma membrane model. Collectively, these findings demonstrate that chain length asymmetry in the hydrophobic region of cationic lipids has an important role in their liposome-DNA interactions at optimal 2:1 and 4:1 lipid to pDNA charge ratios, which in turn modulates their gene transfer properties.
- Hiwale, Ankita A.,Voshavar, Chandrashekhar,Dharmalingam, Priya,Dhayani, Ashish,Mukthavaram, Rajesh,Nadella, Rasajna,Sunnapu, Omprakash,Gandhi, Sivaraman,Naidu,Chaudhuri, Arabinda,Marepally, Srujan,Vemula, Praveen Kumar
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p. 25398 - 25405
(2017/07/10)
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- RADIOACTIVE FLUORINE LABELING PRECURSOR COMPOUND AND METHOD FOR MANUFACTURING RADIOACTIVE FLUORINE LABELED COMPOUND USING THE SAME
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There is provided a labeling precursor compound represented by the following general formula (2): wherein R1 represents an alkynyl group, an alkynyloxy group, an azide group, an azidoalkyl group, an arylazide group, a monocyclic or condensed polycyclic aryl group or a nitrogen-containing heterocycle; R2 and R3 each independently represent an alkyl group or a hydroxyalkyl group which hydroxy group may be protected with a protecting group, and n is an integer of 1 or 2; R6 represents an alkyl group or —CONR11R12 wherein R11 and R12 each independently represent an alkyl group or a monocyclic or condensed polycyclic aryl group; and R4, R5, R7 and R8 each independently represent a hydrogen atom, an alkyl group or an alkoxy group.
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Paragraph 0077; 0080
(2017/03/28)
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- Asymmetric cationic lipid based non-viral vectors for an efficient nucleic acid delivery
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Cationic lipids have been extensively studied for their ability to complex with nucleic acids to condense and consequently deliver them into the cells. However, developing safe and efficient cationic lipids for delivering nucleic acids is still an unmet challenge. Prior structure-activity investigations led to the path to understanding the lipid structure and its transfection efficiency. The trend in the transfection profiles of linker-based lipids is different from linker-less lipids. Influence of unsaturation in the hydrophobic chains has been investigated in linker-based lipids. However, in linker-less lipids, it remains unexplored. Herein, we demonstrate that the designed cationic lipid Lipid S-U with an asymmetric hydrophobic core having one stearyl (18:0) and one oleyl chain (18:1) showed superior transfection efficiency compared to its symmetric counterparts, Lipid S-S (hydrophobic core comprising of two stearyl chains (18:0)), and Lipid U-U (two oleyl chains (18:1)), in vitro. Mechanistic studies involving membrane fusogenicity with FACS revealed that liposomes of Lipid S-U have higher fusogenicity (89%) with B16F10 cell membrane than saturated Lipid S-S (66%) and unsaturated Lipid U-U (70%). Endosomal escape studies with confocal microscopy in HEK 293 cells revealed that lipoplexes of Lipid S-U had a higher endosomal escape and released the genetic payload in cytoplasm more efficiently than saturated Lipid S-S and unsaturated Lipid U-U. These cumulative findings support the notion that higher cellular uptake and endosomal escape resulting from fusogenic liposomes of Lipid S-U play a pivotal role in the higher transfection efficiency of asymmetric Lipid S-U.
- Meka, Rakeshchandra R.,Godeshala, Sudhakar,Marepally, Srujan,Thorat, Ketan,Reddy Rachamalla, Hari Krishna,Dhayani, Ashish,Hiwale, Ankita,Banerjee, Rajkumar,Chaudhuri, Arabinda,Vemula, Praveen Kumar
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p. 77841 - 77848
(2018/06/22)
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- NOVEL LIPIDS AND LIPID NANOPARTICLE FORMULATIONS FOR DELIVERY OF NUCLEIC ACIDS
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Compounds are provided having the following structure: (I) or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof, wherein R1a, R1b, R2a, R2b, R3a, R3b, R4a, R4b, R5, R6, R7, R8, R9, L1, L2, a, b, c, d and e are as defined herein. Use of the compounds as a component of lipid nanoparticle formulations for delivery of a therapeutic agent, compositions comprising the compounds and methods for their use and preparation are also provided.
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Page/Page column 75; 76
(2016/05/02)
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- PROCESS FOR PRODUCTION OF NITROGENATED COMPOUND
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The present invention relates to a process for producing an aliphatic primary amine or an aliphatic secondary amine from an aliphatic alcohol with a high catalytic activity and a high selectivity. In the process for producing an aliphatic amine according to the present invention, a linear, branched, or cyclic aliphatic alcohol having 6 to 22 carbon atoms is contacted with ammonia and hydrogen in the presence of a catalyst formed by supporting a ruthenium component on at least one material selected from the group consisting of (B) a zirconia-containing composite oxide and (C) zirconia surface-treated with a metal by hydrolysis of (A) a ruthenium compound.
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Page/Page column 7
(2009/10/01)
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- A close-packed, highly insulating organic thin monolayer on Si(111)
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A long-chain dialkylated olefin, 2C18 was found to form a close-packed, highly insulating self-assembled monolayer (SAM) on Si(111) via Si-C bond formation. The IR absorption spectra of the 2C18-SAM show that the alkyl chains are densely packed with an all-trans conformation. The threshold voltage to initiate the scanned probe oxidation (SPO) of the 2C18-SAM-covered Si(111) was ca. 9V, which is much higher than the previously reported voltages for organic monolayers on Si or SiO2/Si substrates. Copyright
- Tanaka, Kentaro,Tanaka, Taishi,Hasegawa, Takeshi,Shionoya, Mitsuhiko
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p. 440 - 441
(2008/09/21)
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- PROCESS FOR PRODUCING NITROGEN-CONTAINING COMPOUNDS
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The present invention relates to a process for producing an aliphatic amine, including the step of contacting a linear or branched, or cyclic aliphatic alcohol with ammonia and hydrogen in the presence of a catalyst containing (A) nickel, copper and zirconium components, and (B) at least one metal component selected from the group consisting of elements belonging to Group 3 of the Periodic Table, elements belonging to Group 5 of the Periodic Table and platinum group elements. According to the process of the present invention, an aliphatic primary amine can be produced from an aliphatic alcohol with a high selectivity.
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(2008/06/13)
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- PROCESS FOR PRODUCING NITROGEN-CONTAINING COMPOUNDS
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The present invention relates to a process for producing an aliphatic amine, including the step of contacting a linear or branched, or cyclic aliphatic alcohol with ammonia and hydrogen in the presence of a catalyst containing (A) nickel, copper and zirconium components, and (B) at least one metal component selected from the group consisting of elements belonging to Group 1 of the Periodic Table. According to the process of the present invention, an aliphatic primary amine can be produced from the aliphatic alcohol with a good yield and a high productivity.
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Page/Page column 4
(2008/06/13)
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- PROCESS FOR PRODUCING NITROGEN-CONTAINING COMPOUNDS
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The present invention relates to a process for producing an aliphatic amine, comprising the step of contacting a linear or branched, or cyclic aliphatic alcohol having 6 to 22 carbon atoms with ammonia and hydrogen in the presence of a catalyst formed by supporting at least (A) a ruthenium component produced by hydrolysis of a ruthenium compound on a carrier, or by further supporting, in addition to the component (A), a specific second metal component or a specific third metal component on the carrier. According to the process of the present invention, an aliphatic primary amine can be produced from an aliphatic alcohol with a high catalytic activity and a high selectivity.
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Page/Page column 10-11
(2008/06/13)
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- Anchor dependency for non-glycerol based cationic lipofectins: Mixed bag of regular and anomalous transfection profiles
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Although detailed structure-activity, physicochemical and biophysical investigations in probing the anchor influence in liposomal gene delivery have been reported for glycerol-based transfection lipids, the corresponding investigation for non-glycerol based simple monocationic transfection lipids have not yet been undertaken. Towards this end, herein, we delineate our structure-activity and physicochemical approach in deciphering the anchor dependency in liposomal gene delivery using fifteen new structural analogues (lipids 1-15) of recently reported non-glycerol based monocationic transfection lipids. The C14 analogues in both series 1 (lipids 1-6) and series 2 (lipids 7-15) showed maximum efficiency in transfecting COS-1 and CHO cells. However, the C12 analogue of the ether series (lipid 3) exhibited a seemingly anomalous behavior compared with its transfection efficient C10 and C14 analogues (lipids 2 and 4) in being completely inefficient to transfect both COS-1 and CHO cells. The present structure-activity investigation also convincingly demonstrates that enhancement of transfection efficiencies through incorporation of membrane re-organizing unsaturation elements in the hydrophobic anchor of cationic lipids is not universal but cell dependent. The strength of the interaction of lipids 1-15 with DNA was assessed by their ability to exclude ethidium bromide bound to the DNA. Cationic lipids with long hydrophobic tails were found, in general, to be efficient in excluding EtBr from DNA. Gel to liquid crystalline transition temperatures of the lipids was measured by fluorescence anisotropy measurement technique. In general (lipid 2 being an exception), transfection efficient lipids were found to have their mid transition temperatures at or below physiological temperatures (37°C).
- Singh, Rajkumar Sunil,Mukherjee, Koushik,Banerjee, Rajkumar,Chaudhuri, Arabinda,Hait, Samik Kumar,Moulik, Satya Priya,Ramadas, Yerramsetti,Vijayalakshmi, Amash,Rao, Nalam Madhusudhana
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p. 900 - 909
(2007/10/03)
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- Amphipatic polycarboxylic chelates and complexes with paramagnetic metals as MRI contrast agents
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Substituted polycarboxylic ligand molecules and corresponding metal complexes of said ligands, preferably paramagnetic metals complexes for generating responses in the field of magnetic resonance imaging (MRI). The paramagnetic complexes of the polycarboxylic ligands possess advantageous tensioactive properties and are useful as MRI contrast media in formulations for investigating the blood pool.
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(2010/11/29)
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- Novel series of non-glycerol-based cationic transfection lipids for use in liposomal gene delivery
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A novel series of nontoxic and non-glycerol-based simple monocationic transfection lipids containing one or two hydroxyethyl groups directly linked to the positively charged nitrogen atom were synthesized. The in vitro transfection efficiencies of these new liposomal gene delivery reagents were better than that of lipofectamine, a widely used transfection agent in cationic lipid-mediated gene transfer. The most efficient transfection formulation was observed to be a 1:1:0.3 mol ratio of DHDEAB (N,N-di-n- hexadecyl-N,N-dihydroxyethylammonium bromide): cholesterol:HDEAB (N-n- hexadecyl-N,N-dihydroxyethylammonium bromide) using a DHDEAB-to-DNA charge ratio (+/-) of 0.3:1. Observation of good transfection at charge ratios lower than i suggests that the amphiphile-DNA complex may have net negative charge. Our results reemphasize the important point that in cationic lipid-mediated gene delivery, the overall charge of the lipid-DNA complex need not always be positive. In addition, our transfection results also imply that favorable hydrogen-bonding interactions between the lipid headgroups and the cell surface of biological membranes may have some role for improving the transfection efficiency in cationic lipid-mediated gene delivery.
- Banerjee, Rajkumar,Prasanta Kumar, Das,Srilakshmi, Gollapudi Venkata,Chaudhuri, Arabinda,Nalam Madhusudhana, Rao
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p. 4292 - 4299
(2007/10/03)
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- New lyotropic phases (thermally-reversible organogels) of simple tertiary amines and related tertiary and quaternary ammonium halide salts
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Small concentrations of some structurally simple tertiary amines and related tertiary and quaternary ammonium halide salts form viscoelastic, thermally reversible gels with a wide variety of organic liquids.
- Lu, Liangde,Weiss, Richard G.
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p. 2029 - 2030
(2007/10/03)
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- Process for preparing 1-oxa-3,8-diaza-4-oxo-spiro-[4,5]-decanes
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1-Oxa-3,8-diaza-4-oxo-spiro-[4,5]-decane compounds of the formula STR1 are new light stabilizers for protecting polymers from the damaging effect of UV radiation.
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- Poly-bis-triazinylimides, their preparation
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Poly-bis-triazinylimides of the formula STR1 are prepared from bis-(2,4-dichloro-1,3,5-triazin-6-yl)imides and polyalkylpiperidylamines. They are used as light stabilizers for polymers.
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