- Covalent Radical Pairs as Spin Qubits: Influence of Rapid Electron Motion between Two Equivalent Sites on Spin Coherence
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Ultrafast photodriven electron transfer reactions starting from an excited singlet state in an organic donor-acceptor molecule generate a radical pair (RP) in which the two spins are initially entangled and, in principle, can serve as coupled spin qubits in quantum information science (QIS) applications, provided that spin coherence lifetimes in these RPs are long. Here we investigate the effects of electron transfer between two equivalent sites comprising the reduced acceptor of the RP. A covalent electron donor-acceptor molecule (D-C-A24+) including a p-methoxyaniline donor (D), a 4-aminonaphthalene-1,8-imide chromophoric primary acceptor (C), and a m-xylene bridged cyclophane having two equivalent phenyl-extended viologens (A24+) as a secondary acceptor was synthesized along with the analogous molecule having one phenyl-extended viologen acceptor and a second, more difficult to reduce 2,5-dimethoxyphenyl-extended viologen in a very similar cyclophane structure (D-C-A4+). Photoexcitation of C within each molecule results in subnanosecond formation of D+?-C-A23+? and D+?-C-A3+?. The spin dynamics of these RPs were characterized by time-resolved EPR spectroscopy and magnetic field effects on the RP yield in both CH3CN and CD3CN. The data show that rapid electron hopping within A23+? promotes spin decoherence in D+?-C-A23+? relative to D+?-C-A3+? having a monomeric acceptor, while the interaction of the RP electron spins with the nuclear spins of the solvent have little or no effect on the spin dynamics. These observations provide important information for designing and understanding novel molecular assemblies of spin qubits with long coherence times for QIS applications.
- Wu, Yilei,Zhou, Jiawang,Nelson, Jordan N.,Young, Ryan M.,Krzyaniak, Matthew D.,Wasielewski, Michael R.
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Read Online
- Coordination chemistry of an amine-substituted bis(pyrazolyl)-pyridine ligand: interaction of a peripheral functional group on a coordination cage with the internal contents of the cavity
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The ligand Lan contains two bidentate chelating pyrazolyl-pyridine termini connected to a central aminophenyl ring. In [Ag3(Lan)2](ClO4)3 each ligand coordinates in a pentadentate 2+1+2 man
- Metherell, Alexander J.,Ward, Michael D.
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Read Online
- Design, Synthesis, and Structure-Activity Relationships of Novel Tetrahydroisoquinolino Benzodiazepine Dimer Antitumor Agents and Their Application in Antibody-Drug Conjugates
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A series of tetrahydroisoquinoline-based benzodiazepine dimers were synthesized and tested for in vitro cytotoxicity against a panel of cancer cell lines. Structure-activity relationship investigation of various spacers guided by molecular modeling studie
- Chowdari, Naidu S.,Zhang, Yong,McDonald, Ivar,Johnson, Walter,Langley, David R.,Sivaprakasam, Prasanna,Mate, Robert,Huynh, Tram,Kotapati, Srikanth,Deshpande, Madhura,Pan, Chin,Menezes, Daniel,Wang, Yichong,Rao, Chetana,Sarma, Ganapathy,Warrack, Bethanne M.,Rangan, Vangipuram S.,Mei-Chen, Sung,Cardarelli, Pina,Deshpande, Shrikant,Passmore, David,Rampulla, Richard,Mathur, Arvind,Borzilleri, Robert,Rajpal, Arvind,Vite, Gregory,Gangwar, Sanjeev
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p. 13913 - 13950
(2020/12/02)
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- THERAPEUTIC METHODS
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The invention provides methods and compositions for delivering a nucleic acid to a cell or the cytosol of the target cell. The method includes contacting the cell with, 1) a membrane-destabilizing polymer; and 2) a nucleic acid conjugate. The nucleic acid conjugate includes a targeting ligand bound to an optional linker and a nucleic acid.
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Page/Page column 97-98; 102-103; 106; 109
(2020/05/28)
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- METHODS FOR TREATING HEPATITIS B INFECTIONS
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Certain embodiments of the invention provide a method for identifying a patient that has a higher likelihood of responding to an HBV antigen inhibitor, such a method comprising detecting a hepatitis B virus (HBV) infected patient's genotype at one or more of the IL28B/A associated SNPs described herein, wherein the relevant genotype(s) described herein are indicative of a patient that has a higher likelihood of responding to an HBV antigen inhibitor as compared to an HBV infected patient having different genotypes at these locations.
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Page/Page column 170-171; 177
(2019/04/09)
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- TARGETED COMPOSITIONS
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The invention provides certain nucleic acids (e.g., double stranded siRNA molecules), as well as conjugates that comprise a targeting moiety, a double stranded siRNA, and optional linking groups. Certain embodiments also provide synthetic methods useful for preparing the conjugates. The conjugates are useful to target therapeutic double stranded siRNA to the liver and to treat liver diseases including hepatitis (e.g. hepatitis B and hepatitis D).
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Page/Page column 86; 90; 91; 94; 97
(2018/11/10)
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- Light-responsive bicyclic peptides
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In this paper, we describe a method for the synthesis of light-responsive (LR) bicyclic macrocycles from linear peptides composed of 20 natural amino acids. Small molecules, peptide macrocycles, and protein conjugates that reversibly turn their function on and off in response to visible light enabled the fields of photopharmacology and optochemical genetics. Bioactive LR molecules could be produced by grafting azobenzene or other LR-structures onto molecules with known biological functions (e.g., alpha-helical peptides). It is also possible to discover such LR ligands de novo by selecting compounds with a desired function - such as binding to a target - from a library of LR-compounds or a genetically-encoded (GE) library of LR-macrocycles. The bicyclic topology of ligands offers added value such as improved binding and stability when compared to monocyclic peptides, but approaches for the design of bicyclic light-responsive architectures are limited. To address this need, we developed a tridentate C2-symmetric hydroxyl amine and di-chlorobenzene containing azobenzene (HADCAz) LR-linker with two orthogonally reactive functionalities (chlorobenzyl and hydroxylamine) to convert a linear unprotected peptide into a bicyclic peptide in a one-pot, two-step reaction. This linker reversibly isomerizes from the trans to cis form upon irradiation with blue light (365 nm). The resulting bicyclic peptide contains two loops of amino acids, one of which is constrained with an azobenzene moiety that can change the conformation in response to visible light. A scalable synthetic route to the HADCAz linker allowed us to demonstrate its application in multiple synthetic bicyclic peptides with loops that contain 2-5 amino acids.
- Jafari, Mohammad R.,Yu, Hongtao,Wickware, Jessica M.,Lin, Yu-Shan,Derda, Ratmir
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supporting information
p. 7588 - 7594
(2018/11/02)
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- Supramolecular Anchoring of NCN-Pincer Palladium Complexes into a β-Barrel Protein Host: Molecular-Docking and Reactivity Insights
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Several prochiral NCN-pincer complexes of palladium(II), with hemilabile ligands and a long aliphatic chain, were synthesized and characterized spectroscopically. In some of the complexes, the presence of two different substituents on the N donor atoms ma
- Pocquet, Lucrèce,Vologdin, Nikolay,Mangiatordi, Giuseppe Felice,Ciofini, Ilaria,Nicolotti, Orazio,Thorimbert, Serge,Salmain, Michèle
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p. 3622 - 3634
(2017/08/23)
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- TARGETED NUCLEIC ACID CONJUGATE COMPOSITIONS
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The invention provides conjugates that comprise a targeting moiety, a nucleic acid, and optional linking groups as well as synthetic intermediates and synthetic methods useful for preparing the conjugates. The conjugates are useful to target therapeutic nucleic acids to the liver and to treat liver diseases including hepatitis (e.g. hepatitis B and hepatitis D).
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Page/Page column 59; 64; 68
(2017/11/10)
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- The role of magnetic nanoparticles (MNP) as reducing agents in an MNP-supported Pd-catalyst for the reductive homocoupling of aryl halides
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A palladium pincer catalyst grafted onto the surface of magnetic nanoparticles (MNPs) has been developed. This material effectively catalyzes the reductive homocoupling of various aryl halide substrates, with the MNP support acting as the reducing agent. The catalyst can be recycled up to five times in the absence of additional reducing agent to give almost quantitative yields of biaryl homocoupling products. After the reducing power of the MNP has been depleted, the supported Pd complex remains an effective catalyst for Suzuki-Miyaura cross-coupling.
- Zheng, Jie,Lin, Shengyue,Jiang, Bi-Wang,Marder, Todd B.,Yang, Zhen
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supporting information; experimental part
p. 138 - 144
(2012/03/07)
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- HIV-1 X4 activities of polycationic Viologen based dendrimers by interaction with the chemokine receptor CXCR4: Study of structure-activity relationship
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A series of viologen based dendrimers with polycationic scaffold carrying 10, 18, 26, 42, and 90 charges per molecule were used to determine the structure-activity relationship (SAR) with regard to HIV-1 inhibitory activity. The studies involved five comp
- Asaftei, Simona,Huskens, Dana,Schols, Dominique
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supporting information
p. 10405 - 10413
(2013/02/23)
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- Design, synthesis, docking, and biological evaluation of novel diazide-containing isoxazole- and pyrazole-based histone deacetylase probes
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The design, synthesis, docking, and biological evaluation of novel potent HDAC3 and HDAC8 isoxazole- and pyrazole-based diazide probes suitable for binding ensemble profiling with photoaffinity labeling (BEProFL) experiments in cells is described. Both the isoxazole- and pyrazole-based probes exhibit low nanomolar inhibitory activity against HDAC3 and HDAC8, respectively. The pyrazole-based probe 3f appears to be one of the most active HDAC8 inhibitors reported in the literature with an IC50 of 17 nM. Our docking studies suggest that unlike the isoxazole-based ligands the pyrazole-based ligands are flexible enough to occupy the second binding site of HDAC8. Probes/inhibitors 2b, 3a, 3c, and 3f exerted the antiproliferative and neuroprotective activities at micromolar concentrations through inhibition of nuclear HDACs, indicating that they are cell permeable and the presence of an azide or a diazide group does not interfere with the neuroprotection properties, or enhance cellular cytotoxicity, or affect cell permeability.
- Neelarapu, Raghupathi,Holzle, Denise L.,Velaparthi, Subash,Bai, He,Brunsteiner, Michael,Blond, Sylvie Y.,Petukhov, Pavel A.
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experimental part
p. 4350 - 4364
(2011/09/16)
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- PYRIMIDINE DERIVATIVES
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The invention concerns benzamide compounds of Formula (I), or a pharmaceutically acceptable salt thereof, where R1, ring A, n, R3, and R4 are as defined in the description. The present invention also relates to processes for the preparation of such compounds, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use as an antiproliferative agent in the prevention or treatment of tumours or other proliferative conditions which are sensitive to the inhibition of EphB4, and/or EphA2 and/or Src kinases.
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Page/Page column 102; 104
(2011/04/14)
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- NOVEL BENZODIAZEPINE DERIVATIVES
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The invention relates to novel benzodiazepine derivatives with antiproliferative activity and more specifically to novel benzodiazepines of formula (I) and (II), in which the diazepine ring (B) is fused with a heterocyclic ring (CD), wherein the heterocyclic ring is bicyclic or a compound of formula (III), in which the diazepine ring (B) is fused with a heterocyclic ring (C), wherein the heterocyclic ring is monocyclic. The invention provides cytotoxic dimers of these compounds. The invention also provides conjugates of the monomers and the dimers. The invention further provides compositions and methods useful for inhibiting abnormal cell growth or treating a proliferative disorder in a mammal using the compounds or conjugates of the invention. The invention further relates to methods of using the compounds or conjugates for in vitro, in situ, and in vivo diagnosis or treatment of mammalian cells, or associated pathological conditions.
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Page/Page column 119-120
(2010/08/18)
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- "viologen"dendrimers as antiviral agents: The effect of charge number and distance
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A series of "viologen"derivatives (4,4′-bipyridinium salts) carrying between 1 and 90 charges per molecule have been prepared and investigated for their activity against human immunodeficiency virus (HIV), herpes simplex virus (HSV), vesicular stomatitis, Punta Toro virus, Sindbis virus, Reovirus, and respiratory syncytial viruses. In general, most of the compounds showed good activities against HIV-1 (strain IIIB). In particular, compound 36 exhibited the highest in vitro activity and selectivity index against HIV-1 (strain IIIB) (EC50 = 0.26 ± 0.08 μM, SI = 75.7) in MT-4 cells. The results imply that the antiviral activity requires an optimal number and distance of the positive charges.
- Asaftei, Simona,De Clercq, Erik
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supporting information; experimental part
p. 3480 - 3488
(2010/09/04)
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- Preparation of tethered palladium catalysis supported on gold(111) and its surface characterization by X-ray photoelectron spectroscopy (XPS)
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Chelated tethering ligands were confined on a Au(111) substrate, and the confinement of the ligands was confirmed by X-ray photoelectron spectroscopy (XPS). Palladium was anchored to the ligands to construct heterogeneous (Pd)-L-Au(111) catalysts (L = lig
- Gulam, Rabbani M.,Hamada, Masahiro,Takamiya, Ikuko,Shimoda, Masahiko,Shuto, Satoshi,Nishida, Atsushi,Tsukamoto, Shiro,Arisawa, Mitsuhiro
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scheme or table
p. 1012 - 1018
(2009/04/13)
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- Evidence that SCS pincer Pd(II) complexes are only precatalysts in Heck catalysis and the implications for catalyst recovery and reuse
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SCS-pincer Pd(II) complexes have been covalently immobilized onto porous silica, cross-linked polymer (Merrifield resin) and soluble poly(norbornene) supports via either amide or urea linkages and evaluated in the Heck coupling of iodobenzene with n-butyl acrylate. Kinetic experiments and poisoning studies indicate that in all cases the pincer complexes merely act as precatalysts. Contrary to literature reports, there is no evidence for catalysis by the intact amide-linked SCS-Pd(II) complexes under any conditions studied here.
- Yu, Kunquan,Sommer, William,Richardson, John M.,Weck, Marcus,Jones, Christopher W.
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p. 161 - 171
(2007/10/03)
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- Tridentate SCS palladium(II) complexes: New, highly stable, recyclable catalysts for the Heck reaction
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A new pincer-type SCS ligand containing Pd(II) is a simple, robust catalyst for Heck chemistry using a variety of alkene acceptors and aryl iodides. It is less active with aryl bromides. While certain palladium-(II) species insert slowly into the aryl C-H bond of an unsubstituted version of this ligand, the introduction of activating groups into the 5 position of the aromatic ring readily allows quantitative metal insertion. These ligands were synthesized and attached to soluble polymers by simple modification of inexpensive starting materials. For example, both 5-oxy and 5-amido SCS ligands were successfully appended to 5000 Mn poly-(ethylene glycol) via ether or amide linkages, respectively. Both the 5-oxo and 5-amido complexes are active as Heck catalysts in DMF solution in air. The PEG-bound 5-amido-SCS-Pd complex was recycled via solvent precipitation three times with no observed catalyst deactivation. While the 5-amido-SCS-Pd complexes are very robust, their 5-oxo counterparts decompose slowly under certain conditions. These SCS catalysts are analogous to PCP-type catalysts previously reported in the literature but avoid the requirement of an air-sensitive phosphine synthesis.
- Bergbreiter, David E.,Osburn, Philip L.,Liu, Yun-Shan
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p. 9531 - 9538
(2007/10/03)
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- Synthesis of achiral linker reagents for direct labelling of oligonucleotides on solid supports
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Full experimental procedures for the synthesis of a series of new functional linker reagents (14-16) and solid supports (11-13) are reported. The achiral linker reagents and supports can be used for high yield incorporation of free amino groups, fluorescein or biotin into DNA oligomers.
- Behrens, Carsten,Dahl, Otto
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p. 291 - 305
(2007/10/03)
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- Selective hydrogenolysis of bis(hydroxymethyl)aromatic compounds
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Selective hydrogenolysis of symmetric bis(hydroxymethyl)aromatic compounds has been performed over Raney nickel in alkaline solution for 24-36 h at 20°C. The yield of the corresponding monohydrogenolysis product was in the range of 75-96%. The usefulness of the reaction was demonstrated by the synthesis of 4-(bromomethyl)benzoic acid.
- Behrens,Egholm,Buchardt
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p. 1235 - 1236
(2007/10/02)
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- Electron Donor-Acceptor Compounds, XXXVIII. Electron Donor-Acceptor Metacyclophanes: Synthesis, Structure, and Charge-Transfer Spectra
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Donor-acceptor metacyclophanes 1-4 as well as 24 were synthesized via the correspondingly substituted 2,11-dithiametacyclophanes 8, 13, and 25 and their disulfone derivatives.The anti-compound 1 and the syn-isomer 2 were isolated and characterized.The attempt of the analogous synthesis of 5/6 via 21 and 22 failed since with loss of the intraanular substituents and by transanular C-C formation the tetrahydropyrene derivative 23 was formed.For spectroscopic comparison 27 was prepared via 28.- X-Ray structure analyses of 21, 24, and 25 were performed.The molecular structures of these compounds are discussed under the aspects of sterical strain and donor-acceptor overlap.The structure analyses confirm the assignment to the syn- and anti-series as derived from 1H NMR.- Absorption spectra of 1, 2, 3, and 24 were measured; especially the surprising absorption behaviour of the isomers 1 and 2 with very different donor-acceptor overlap was of interest.Determination of the solvent dependence of fluorescence made sure that the absorptions dealt with are indeed charge-transfer transitions.
- Staab, Heinz A.,Schanne, Lothar,Krieger, Claus,Taglieber, Volker
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p. 1204 - 1229
(2007/10/02)
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