Evolution of Abiotic Cubane Chemistries in a Nucleic Acid Aptamer Allows Selective Recognition of a Malaria Biomarker

Total Page:16

File Type:pdf, Size:1020Kb

Evolution of Abiotic Cubane Chemistries in a Nucleic Acid Aptamer Allows Selective Recognition of a Malaria Biomarker Evolution of abiotic cubane chemistries in a nucleic acid aptamer allows selective recognition of a malaria biomarker Yee-Wai Cheunga,1, Pascal Röthlisbergerb,1, Ariel E. Mechalyc, Patrick Weberc, Fabienne Levi-Acobasb, Young Loa, Alvin W. C. Wonga, Andrew B. Kinghorna, Ahmed Haouzc, G. Paul Savaged, Marcel Hollensteinb,2,3, and Julian A. Tannera,2,3 aSchool of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; bInstitut Pasteur, Laboratory for Bioorganic Chemistry of Nucleic Acids, Department of Structural Biology and Chemistry, CNRS UMR-3523, 75015 Paris, France; cCrystallography Platform-C2RT, Department of Structural Biology and Chemistry, CNRS UMR-3528, Institut Pasteur, 75015 Paris, France; and dCSIRO Manufacturing, Clayton, VIC 3168, Australia Edited by Jack W. Szostak, Massachusetts General Hospital, Boston, MA, and approved May 31, 2020 (received for review February 20, 2020) Nucleic acid aptamers selected through systematic evolution of aptamers (18, 20–23). Other approaches include aptamers with ligands by exponential enrichment (SELEX) fold into exquisite artificially expanded genetic information systems going beyond globular structures in complex with protein targets with diverse the simple four building blocks of natural nucleic acids (24), even translational applications. Varying the chemistry of nucleotides most recently to the eight-building-block Hachimoji system (25). allows evolution of nonnatural nucleic acids, but the extent to Nucleobases have also been modified but have often been re- which exotic chemistries can be integrated into a SELEX selection stricted to mimics of amino acid side chains (13, 26, 27) or small to evolve nonnatural macromolecular binding interfaces is unclear. hydrophobic aromatic moieties (28, 29). Perhaps the most im- Here, we report the identification of a cubane-modified aptamer pressive demonstration of translational cross-proteome aptamer (cubamer) against the malaria biomarker Plasmodium vivax lactate specificity are the SOMAmers (slow off-rate modified aptamers) dehydrogenase (PvLDH). The crystal structure of the complex re- (30), which enabled quantification of over 3,000 plasma proteins veals an unprecedented binding mechanism involving a multicu- bane cluster within a hydrophobic pocket. The binding interaction to create a genomic atlas of the human plasma proteome (31). is further stabilized through hydrogen bonding via cubyl hydro- Such SOMAmers include a simple modification where instead of gens, previously unobserved in macromolecular binding inter- dT they bear dU functionalized at the 5-position of the nucleo- faces. This binding mechanism allows discriminatory recognition base with protein-like benzyl/2-napthyl/3-indolyl-carboxamide of P. vivax over Plasmodium falciparum lactate dehydrogenase, that confer some hydrophobic and/or base stacking character to thereby distinguishing these highly conserved malaria biomarkers for diagnostic applications. Together, our data demonstrate that Significance SELEX can be used to evolve exotic nucleic acids bearing chemical functional groups which enable remarkable binding mechanisms We report the identification of a cubane-modified aptamer which have never been observed in biology. Extending to other (cubamer) against the malaria biomarker Plasmodium vivax exotic chemistries will open a myriad of possibilities for functional lactate dehydrogenase (PvLDH). The cubamer contains the nucleic acids. benzene isostere cubane, which is entirely alien to biology. The crystal structure of the cubamer–protein complex reveals a modified aptamer | SELEX | X-ray crystallography | cubane | malaria binding mechanism involving the formation of an unprece- diagnosis dented cubane pocket and an unusual C–H···O hydrogen bond. Importantly, the cubamer is capable of distinguishing the irected evolution of nucleic acids through the iterative PvLDH from the Plasmodium falciparum LDH despite a very Dprocess of SELEX (1, 2) (selective evolution of ligands by high sequence homology, which is impossible for unmodified exponential enrichment) provides routes to aptamers with ex- aptamers. Finally, we have used the cubamer to detect PvLDH quisite structures that cannot be otherwise imagined or designed in a mimetic clinical situation. This approach blending medicinal (3). Even using the simple natural nucleotides of DNA and RNA chemistry and Darwinian evolution can easily be extended to one can select and evolve aptamers with nanomolar and even other nonnatural, exotic functional groups. picomolar binding affinities and surprising discriminatory speci- ficity (4). Such aptamers are finding applications in therapeutics Author contributions: Y.-W.C., P.R., M.H., and J.A.T. designed research; Y.-W.C., P.R., A.E.M., P.W., F.L.-A., Y.L., A.W.C.W., A.B.K., and A.H. performed research; G.P.S. contrib- (5), diagnostics (6), biosensing (7), and nanotechnology (8) and uted new reagents/analytic tools; Y.-W.C., P.R., A.E.M., F.L.-A., Y.L., A.B.K., A.H., M.H., and can display numerous advantages relative to antibodies (9). J.A.T. analyzed data; and Y.-W.C., P.R., M.H., and J.A.T. wrote the paper. The chemistries of canonical DNA and RNA can be limiting Competing interest statement: J.A.T. is a scientific advisor for Zio Health, and J.A.T. and when one compares them to antibodies (10). Postselection A.B.K. are founders of Jushan Bio. chemical modification can aid in vivo stability and residence time This article is a PNAS Direct Submission. (11, 12) and can facilitate binding to problematic targets such as Published under the PNAS license. – glycoproteins or proteins with low isoelectric points (13 15). Data deposition: The crystal structure of the cubamer–target complex has been deposited However, these post-SELEX approaches often come at the ex- in the Protein Data Bank, http://www.wwpdb.org/ (PDB ID code 6TXR). pense of a loss of binding affinity and specificity. In contrast, 1Y.-W.C. and P.R. contributed equally to this work. — 2 preselection chemical modification where modified nucleo- M.H. and J.A.T. contributed equally to this work. — tides are directly included in the SELEX process truly opens 3To whom correspondence may be addressed. Email: [email protected] or up directed evolution to extending the repertoire of aptamer- [email protected]. mediated molecular recognition (16–19). Many chemical modi- This article contains supporting information online at https://www.pnas.org/lookup/suppl/ fications have been directed at the level of the sugar-phosphate doi:10.1073/pnas.2003267117/-/DCSupplemental. backbone in order to improve the nuclease resistance of First published July 6, 2020. 16790–16798 | PNAS | July 21, 2020 | vol. 117 | no. 29 www.pnas.org/cgi/doi/10.1073/pnas.2003267117 Downloaded by guest on September 25, 2021 the nucleic acid (10). New, engineered polymerases are not re- Investigating Compatibility of dUCTP with Primer Extension and PCR. quired to cope with unnatural chemistry introduced at position 5 We next asked whether dUCTP 11 (Fig. 1B) would be compatible of pyrimidines (32). Base modified nucleotides have also been with enzymatic DNA synthesis under primer extension (PEX) proposed as elements in an RNA world to promote the catalytic reaction and PCR conditions. We used the 15-nucleotide-long, 5′ activity of RNA-based catalysts (33). Alternatively, click chem- 6-FAM (fluorescein)-labeled primer P1 annealed to template T1 istry with alkyne-modified nucleotides can be used to select for (see SI Appendix for sequence composition) then investigated the nucleobase-modified aptamers (34). Through such approaches, ability of various polymerases to perform a PEX reaction with a nucleobase-modified aptamers with nonnatural chemistries be- mixture of either four natural triphosphates or three natural C come accessible. One can then take advantage of the exponential triphosphates together with dU TP replacing thymidine 5′- enrichment and mutation enabled by the PCR to allow Dar- triphosphate (dTTP) (SI Appendix, Fig. S20). This analysis C winian molecular evolution, yet inclusion of more exotic un- revealed that most polymerases accepted dU TP as a substrate natural functional groups allows evolutionary experiments well and the primer was extended by 16 nucleotides (accounting for beyond the confined chemistries familiar of biology. the incorporation of four modified nucleotides). When a longer Here, we present an effort to stretch the idea of nonnatural template was used (the 79-mer template T2) which would re- P2 chemistry within an evolutionary nucleic acid aptamer selection quire extension of primer by 60 nucleotides a clear by applying the in vitro evolutionary technique of SELEX to higher-molecular-weight product is formed in the reaction with C SI macromolecular chemistries entirely alien to biology. We per- dU TP when compared to that with natural triphosphates ( Appendix form an aptamer selection incorporating unusual cubane- , Figs. S21 and S22). Several polymerases including exo− Bst modified nucleotides, presenting structural data, mechanistic Therminator, Vent ( ), Deep Vent, Taq, , Klenow, Q5 determination, and diagnostic application of cubane-modified DNA polymerase, and phi29 were all capable of forming the exo− nucleic acid aptamers, hereafter called cubamers. The extraor- expected cubane-modified product. However, Vent ( ) appeared to most consistently produce highest-yield product (SI dinary platonic solid cubanes have intrigued chemists for de- Appendix cades (35–37)
Recommended publications
  • Cubane and Triptycene As Scaffolds in the Synthesis of Porphyrin Arrays
    Cubane and Triptycene as Scaffolds in the Synthesis of Porphyrin Arrays Submitted by Gemma M. Locke B.A. (Mod.) Medicinal Chemistry Trinity College Dublin, Ireland A thesis submitted to the University of Dublin, Trinity College for the degree of Doctor of Philosophy Under the Supervision of Prof. Dr. Mathias O. Senge University of Dublin, Trinity College September 2020 Declaration I declare that this thesis has not been submitted as an exercise for a degree at this or any other university and it is entirely my own work. I agree to deposit this thesis in the University’s open access institutional repository or allow the Library to do so on my behalf, subject to Irish Copyright Legislation and Trinity College Library conditions of use and acknowledgement. I consent to the examiner retaining a copy of the thesis beyond the examining period, should they so wish. Furthermore, unpublished and/or published work of others, is duly acknowledged in the text wherever included. Signed: ____________________________________________ March 2020 Trinity College Dublin ii Summary The primary aim of this research was to synthesise multichromophoric arrays that are linked through rigid isolating units with the capacity to arrange the chromophores in a linear and fixed orientation. The electronically isolated multichromophoric systems could then ultimately be tested in electron transfer studies for their applicability as photosynthesis mimics. Initially, 1,4-diethynylcubane was employed as the rigid isolating scaffold and one to two porphyrins were reacted with it in order to obtain the coupled product(s). Pd-catalysed Sonogashira cross-coupling reactions were used to try and achieve these bisporphyrin complexes.
    [Show full text]
  • And 5,10,15,20-Tetraalkylporphyrins: Implications For
    336 J. Am. Chem. SOC.1988, 110, 336-342 values being Ai,(IH) = 127.2 G and gs0= 2.0042. Since these intermediates produced under reactive laser sputtering21and other results are very similar to those calculated from the neon data, high-energy condition^.^' The use of the neon ESR matrix namely, Ais0(lH) = 128.6 G and giso= 2.0038, it is reasonable technique for studying ion products formed injon-neutral reactions to conclude that these parameters are characteristic of the un- has also been demonstrated for the following reactions which are complexed cation irrespective of the nature of the matrix. Con- important in stratospheric chemistry: CO + CO' -+ C202+,42 sequently, the significantly different parameters observed for the N2 + N2+- N4+,43N2 + CO+ - N2CO+,'and O2 + 02+- cation above 120 K in the CFC1, matrix (Table 111) now become 04+.44 anomalous for a dissociated cation. On the other hand, these 120 K parameters are just what would be expected if the complex Acknowledgment. The neon matrix ESR experiments were persists and the loss of fine structure results simply from a motional conducted at Furman University with support from the National averaging of the 35Cl hyperfine tensor components. Science Foundation (CHE-8508085), the General Electric Except for a recent investigation of the cubane radical cation Foundation, the Amoco Foundation, and Research Corporation. (C8H8+),39the acetaldehyde ion is the largest cation studied to A new ESR spectrometer was made possible by a chemistry date by the neon matrix ESR method. Given the high resolution equipment grant to Furman University from the Pew Memorial that can be achieved in neon and the chance of preferential Trust.
    [Show full text]
  • LIST of PUBLICATIONS of JOSEF MICHL B: Book P: Patent C
    LIST OF PUBLICATIONS OF JOSEF MICHL B: Book P: Patent C: Communication R: Review or Chapter in a Book P 1. Kopecký, J.; Michl, J. "Zpùsob výroby pyrrolo(2,3-d)-pyrimidinù", Czechoslovak patent no. 97821, August 11, 1959. C 2. Zuman, P.; Michl, J. "Role of Keto-Enol Tautomerism in the Polarographical Reduction of Some Carbonyl Compounds", Nature 1961, 192, 655. C 3. Horák, V.; Michl, J.; Zuman, P. "A Contribution to the Studies of Elimination Reactions of Mannich Bases, Using Polarographic Method", Tetrahedron Lett. 1961, 744. C 4. Zahradník, R.; Michl, J.; Koutecký, J. "Fluoranthene-like Hydrocarbons: MO-LCAO Study of Electronic Spectra, Charge-Transfer Spectra and Polarographic Reduction", J. Chem. Soc. 1963, 4998. 5. Koutecký, J.; Hochman, P.; Michl, J. "Calculation of Electronic Spectra of Non-Alternant Conjugated Hydrocarbons by the Semiempirical Method of Limited Configuration Interaction", J. Chem. Phys. 1964, 40, 2439. 6. Zahradník, R.; Michl, J.; Koutecký, J. "Tables of Quantum Chemical Data. II. Energy Characteristics of Some Non-Alternant Hydrocarbons", Collect. Czech. Chem. Commun. 1964, 29, 1932. 7. Zahradník, R.; Michl, J.; Koutecký, J. "Tables of Quantum Chemical Data. III. Molecular Orbitals of Some Fluoranthene-like Hydrocarbons, Cyclopentadienyl, and Some of its Benzo and Naphtho Derivatives", Collect. Czech. Chem. Commun. 1964, 29, 3184. 8. Zahradník, R.; Michl, J. "Electronic Structure of Non-Alternant Hydrocarbons, Their Analogues and Derivatives. Introductory Remarks", Collect. Czech. Chem. Commun. 1965, 30, 515. 9. Zahradník, R.; Michl, J. "Electronic Structure of Non-Alternant Hydrocarbons, Their Analogues and Derivatives. I. A Theoretical Treatment of Reid's Hydrocarbons", Collect. Czech. Chem. Commun.
    [Show full text]
  • Structure and Bonding of New Boron and Carbon Superpolyhedra
    Structural Chemistry (2019) 30:805–814 https://doi.org/10.1007/s11224-019-1279-5 ORIGINAL RESEARCH Structure and bonding of new boron and carbon superpolyhedra Olga A. Gapurenko1 & Ruslan M. Minyaev1 & Nikita S. Fedik2 & Vitaliy V. Koval1 & Alexander I. Boldyrev2 & Vladimir I. Minkin1 Received: 16 November 2018 /Accepted: 1 January 2019 /Published online: 10 January 2019 # Springer Science+Business Media, LLC, part of Springer Nature 2019 Abstract Using the DFT methods, we computationally predict the stability of cage compounds E4nRn (E = B, C; R = H, F; n = 4, 8, 12, 24) based on Platonic bodies and Archimedean polyhedrons in which all vertices are replaced by tetrahedral E4R fragments. Cage compounds B60R12 and C60 with pyramidal units B5RorC5 are also examined and it is shown that only boron compounds are stable. The nature of chemical bonding in the discussed compounds is analyzed using the AdNDP and NBO methods. The hydrocarbons have classical 2c-2e C-C σ-bonds, while the boron compounds are formed by the polyhedral units with the delocalized multicenter bonds which connected three and more boron atoms. The new example of spherical aromaticity accord- 2 ing to the 2(N+1) rule in the case of B16F4 with multicenter 16c-2e bonds are revealed. Stable compound B60H12 contains 12 5c- 2e B-B bonds. Keywords Сage clusters . Chemical bonding . 3c-2e bond . Spherical aromaticity . AdNDP . NBO Construction of novel allotropic forms of carbon based on was proposed [1] as the system with the same symmetry as the tetrahedrane- and cubane-like building blocks was pro- sp3-carbon to replace the carbon atoms in the diamond posed by Burdett and Lee [1] and by Johnston and lattice.
    [Show full text]
  • Advanced Physical Techniques in Inorganic Chemistry: Probing Small Molecule Activation
    Advanced Physical Techniques in Inorganic Chemistry: Probing Small Molecule Activation The Harvard community has made this article openly available. Please share how this access benefits you. Your story matters Citation Anderson, Bryce L. 2016. Advanced Physical Techniques in Inorganic Chemistry: Probing Small Molecule Activation. Doctoral dissertation, Harvard University, Graduate School of Arts & Sciences. Citable link http://nrs.harvard.edu/urn-3:HUL.InstRepos:33493292 Terms of Use This article was downloaded from Harvard University’s DASH repository, and is made available under the terms and conditions applicable to Other Posted Material, as set forth at http:// nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of- use#LAA Advanced Physical Techniques in Inorganic Chemistry: Probing Small Molecule Activation A dissertation presented by Bryce L. Anderson To The Department of Chemistry and Chemical Biology in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the subject of Chemistry Harvard University Cambridge, Massachusetts May 2016 © 2016 Bryce L. Anderson All rights reserved Dissertation Advisor: Professor Daniel G. Nocera Bryce L. Anderson Advanced Physical Techniques in Inorganic Chemistry: Probing Small Molecule Activation Abstract Robust and efficient catalysts are necessary for realizing chemical energy storage as a solution for the intermittency associated with renewable energy sources. To aid in the development of such catalysts, physical methods are used to probe the photochemistry of small molecule activation in the context of solar-to-fuels cycles. Three systems are studied in the context of HX splitting (X=Br, Cl): polypyridyl nickel complexes, NiX3(LL) (LL = bidentate phosphine) complexes, and dirhodium phosphazane complexes.
    [Show full text]
  • Synthetic Advances in the C‐H Activation of Rigid Scaffold Molecules
    Synthesis Review Synthetic Advances in the C‐H Activation of Rigid Scaffold Molecules Nitika Grovera Mathias O. Senge*a a School of Chemistry, Trinity College Dublin, The University of Dublin, Trinity Biomedical Sciences Institute, 152–160 Pearse Street, Dublin 2, Ireland [email protected] Dedicated to Prof. Dr. Henning Hopf Received: only recall the epic endeavors involved in Eaton’s cubane Accepted: Published online: synthesis,3 Parquette’s preparation of dodecahedrane, DOI: Prinzbach’s pagodane route thereto, or Maier’s synthesis of Abstract The remarkable structural and electronic properties of rigid non‐ tetra-tert-butyltetrahedrane.4 conjugated hydrocarbons afford attractive opportunities to design molecular building blocks for both medicinal and material applications. The bridgehead positions provide the possibility to append diverse functional groups at specific angles and in specific orientations. The current review summarizes the synthetic development in CH functionalization of the three rigid scaffolds namely: (a) cubane, (b) bicyclo[1.1.1]pentane (BCP), (c) adamantane. 1 Introduction 2 Cubane 2.1 Cubane Synthesis 2.2 Cubane Functionalization 3 BCP 3.1 BCP Synthesis 3.2 BCP Functionalization 4 Adamantane 4.1 Adamantane Synthesis 4.2 Adamantane Functionalization 5 Conclusion and Outlook Key words Cubane, bicyclo[1.1.1]pentane, adamantane, rigid scaffolds, CH‐ functionalization. Figure 1 The structures of cubane, BCP and adamantane and the five platonic hydrocarbon systems. The fascinating architecture of these systems significantly 1 Introduction differs from scaffolds realized in natural compounds. Hence, they attracted considerable attention from synthetic and The practice of synthetic organic chemistry of non-natural physical organic chemists to investigate their properties and to compounds with rigid organic skeletons provides a deep establish possible uses.3,5 Significantly, over the past twenty understanding of bonding and reactivity.
    [Show full text]
  • Cheminformatics for Genome-Scale Metabolic Reconstructions
    CHEMINFORMATICS FOR GENOME-SCALE METABOLIC RECONSTRUCTIONS John W. May European Molecular Biology Laboratory European Bioinformatics Institute University of Cambridge Homerton College A thesis submitted for the degree of Doctor of Philosophy June 2014 Declaration This thesis is the result of my own work and includes nothing which is the outcome of work done in collaboration except where specifically indicated in the text. This dissertation is not substantially the same as any I have submitted for a degree, diploma or other qualification at any other university, and no part has already been, or is currently being submitted for any degree, diploma or other qualification. This dissertation does not exceed the specified length limit of 60,000 words as defined by the Biology Degree Committee. This dissertation has been typeset using LATEX in 11 pt Palatino, one and half spaced, according to the specifications defined by the Board of Graduate Studies and the Biology Degree Committee. June 2014 John W. May to Róisín Acknowledgements This work was carried out in the Cheminformatics and Metabolism Group at the European Bioinformatics Institute (EMBL-EBI). The project was fund- ed by Unilever, the Biotechnology and Biological Sciences Research Coun- cil [BB/I532153/1], and the European Molecular Biology Laboratory. I would like to thank my supervisor, Christoph Steinbeck for his guidance and providing intellectual freedom. I am also thankful to each member of my thesis advisory committee: Gordon James, Julio Saez-Rodriguez, Kiran Patil, and Gos Micklem who gave their time, advice, and guidance. I am thankful to all members of the Cheminformatics and Metabolism Group.
    [Show full text]
  • Chimica Industriale “Toso Montanari”
    Alma Mater Studiorum - Università di Bologna SCUOLA DI SCIENZE Dipartimento di Chimica Industriale “Toso Montanari” Corso di Laurea Magistrale in Chimica Industriale Classe LM-71 - Scienze e Tecnologie della Chimica Industriale Supporting Cubane’s Renaissance: Metathesis reactions on 4-iodo-1-vinylcubane and Stetter reaction on 1-iodocubane-4-carboxaldehyde Tesi di laurea sperimentale CANDIDATO RELATORE Andrea Fasolini Chiar.mo Prof. Paolo RIghi CORRELATORE Prof. Mathias O. Senge ___________________________________________________________________________________________________________ _____________ Anno Accademico 2015-2016 ___________________________________________________________________________________________________________ _____________ 1 2 Abstract Cubane is a peculiar cube-shaped alkane molecule with a rigid, regular structure. This makes it a good scaffold, i.e. a molecular platform to which the substituents are arranged in a specific and fixed orientation. Moreover, cubane has a body diagonal of 2.72 Å, very similar to the distance across the benzene ring, i.e. 2.79 Å. Thus, it would be possible to use cubane as a scaffold in medicinal and material chemistry as a benzene isostere 1,2. This could lead to advantages in terms of solubility and toxicity and could provide novel properties. For this purpose, the possibility of performing “modern organic chemistry” on the cubane scaffold has to be studied. This project was entirely carried out in the framework of the Erasmus+ mobility programme at the Trinity College (Dublin, IRL) under the supervision of prof. M. O. Senge. The main goal of this project was to widen the knowledge on cubane chemistry. In particular, it was decided to test reactions that were never applied to the scaffold before, such as metathesis of 4-iodo-1-vinylcubane and Stetter reaction of 1-iodocubane-4- carboxaldehyde.
    [Show full text]
  • Complex Metal Hydrides for Hydrogen, Thermal and Electrochemical Energy Storage
    energies Review Complex Metal Hydrides for Hydrogen, Thermal and Electrochemical Energy Storage Kasper T. Møller 1 ID , Drew Sheppard 1,2, Dorthe B. Ravnsbæk 3 ID , Craig E. Buckley 2, Etsuo Akiba 4,5,6, Hai-Wen Li 1,4,5,7,* and Torben R. Jensen 1,* 1 Interdisciplinary Nanoscience Center (iNANO) and Department of Chemistry, Aarhus University, DK-8000 Aarhus, Denmark; [email protected] (K.T.M.); [email protected] (D.S.) 2 Department of Physics and Astronomy, Fuels and Energy Technology Institute, Curtin University, GPO Box U1987, Perth, WA 6845, Australia; [email protected] 3 Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark; [email protected] 4 International Research Center for Hydrogen Energy, Kyushu University, Fukuoka 819-0395, Japan; [email protected] 5 WPI International Institute for Carbon Neutral Energy Research (WPI-I2CNER), Kyushu University, Fukuoka 819-0395, Japan 6 Department of Mechanical Engineering, Faculty of Engineering, Kyushu University, Fukuoka 819-0395, Japan 7 Kyushu University Platform of Inter/Transdisciplinary Energy Research, Fukuoka 819-0395, Japan * Correspondence: [email protected] (H.-W.L.); [email protected] (T.R.J.) Academic Editor: Haolin Tang Received: 18 September 2017; Accepted: 12 October 2017; Published: 18 October 2017 Abstract: Hydrogen has a very diverse chemistry and reacts with most other elements to form compounds, which have fascinating structures, compositions and properties. Complex metal hydrides are a rapidly expanding class of materials, approaching multi-functionality, in particular within the energy storage field.
    [Show full text]
  • Dft Study of Titanium Cubane and Molybdenum Sulphide Compounds
    UNIVERSITAT 2004 ROVIRA I VIRGILI DFT STUDY OF TITANIUM CUBANE AND MOLYBDENUM SULPHIDE COMPOUNDS José Gracia Budría Departament de Química Física i Inorgànica DFT STUDY OF TITANIUM CUBANE AND MOLYBDENUM SULPHIDE COMPOUNDS José Gracia Budría Memoria presentada para optar al título de Doctor en Química UNIVERSITAT ROVIRA I VIRGILI DFT STUDY OF TITANIUM CUBANE AND MOLYBDENUM SULPHIDE COMPOUNDS. Autor: José Manuel Gracia Budria ISBN: 978-84-690-6751-2 / DL: T.1196-2007 UNIVERSITAT ROVIRA I VIRGILI DFT STUDY OF TITANIUM CUBANE AND MOLYBDENUM SULPHIDE COMPOUNDS. Autor: José Manuel Gracia Budria ISBN: 978-84-690-6751-2 / DL: T.1196-2007 El Dr. Josep Maria Poblet Rius, catedrático de Química Física del departamento de Química Física i Inorgànica de la Universitat Rovira i Virgili; y el Dr. José Pedro Sarasa Solano, profesor titular de Química Física del Departamento de Química Física y Orgánica de la Universidad de Zaragoza CERTIFICAN: Que la presente Memoria titulada: “DFT Study of Titanium Cubane and Molybdenum Sulphide Compounds” ha sido realizada en el departamento de Química Física i Inorgànica de la Universitat Rovira i Virgili, por el licenciado en Ciencias Químicas D. José Gracia Budría, bajo nuestra dirección y autorizamos su presentación para obtener el grado de doctor. Tarragona, 25 de marzo de 2004 Dr. Josep Maria Poblet Rius Dr. José Pedro Sarasa Solano III UNIVERSITAT ROVIRA I VIRGILI DFT STUDY OF TITANIUM CUBANE AND MOLYBDENUM SULPHIDE COMPOUNDS. Autor: José Manuel Gracia Budria ISBN: 978-84-690-6751-2 / DL: T.1196-2007 UNIVERSITAT ROVIRA I VIRGILI DFT STUDY OF TITANIUM CUBANE AND MOLYBDENUM SULPHIDE COMPOUNDS.
    [Show full text]
  • Generation and Reactions of an Octacyclic Hindered Pyramidalized Alkene
    Generation and reactions of an octacyclic hindered pyramidalized alkene. Pelayo Camps,*† David Lozano,† Carla Barbaraci,† Merce Font-Bardia,§‖ F. Javier Luque,‡ Carolina Estarellas‡ † Laboratori de Química Farmacèutica (Unitat Associada al CSIC), Facultat de Farmàcia i Ciències de l’Alimentació, and Institut de Biomedicina (IBUB), Universitat de Barcelona, Av. Joan XXIII 2731, 08028 Barcelona (Spain). § Departament de Cristal·lografia, Mineralogia i Dipòsits Minerals, Universitat de Barcelona, Martí Franquès s/n, 08028 Barcelona (Spain). ‖ Unitat de Difracció de RX, Centres Científics i Tecnològics de la Universitat de Barcelona (CCiTUB), Solé i Sabarís 13, 08028 Barcelona (Spain) ‡ Departament de Nutrició, Ciències de l’Alimentació i Gastronomia, Universitat de Barcelona, Av. Prat de la Riba 171, 08921 Santa Coloma de Gramenet (Spain) and Institut de Biomedicina (IBUB), Universitat de Barcelona, Av. Joan XXIII 2731, 08028 Barcelona (Spain). Abstract. Octacyclo[10.6.1.01,10.03,7.04,9.08,19.011,16.013,17]nonadeca-5,8,14-triene (27) a hindered pyramidalized alkene, has been generated from a diiodide precursor. Contrary to the usual behavior of known pyramidalized alkenes, no Diels-Alder adducts were obtained from the present alkene when it was generated by different standard procedures in the presence of different dienes. However, products derived from the 1 reduction, t-BuLi addition, condensation with the solvent, or dimerization, were isolated from these reactions, depending on the conditions used to generate it. No [2+2] cross product among this pyramidalized alkene and tricyclo[3.3.1.03,7]non-3(7)-ene was formed when a mixture of the corresponding precursor diiodides was reacted with sodium amalgam.
    [Show full text]
  • Abstract Chemistry White, Sidney Gloria Bs Delaware
    ABSTRACT CHEMISTRY WHITE, SIDNEY GLORIA B.S. DELAWARE STATE COLLEGE, 1966 (I) THE EFFECT OF SOLVENT AND SHIF1’ PEAGENTS..ON.VTH. PROTON MAGNETIC RE SONANCE SPECTRA OF SONE ~ZUBANE DERIVATIVES (II) ON THE MECHANISM OF PHOTODIMERIZATION OF V CYCLOPENTADIENE Advisor: Professor Thomas W. Cole, Jr. Thesis dated December 1976 Part I of this thesis is concerned with the effect of solvent, sub stituents and the shift reagent Eu(DPM)3 on the proton magnetic resonance spectrum of several 1,4-disubstituted cubane derivatives. The chemical shift of the cubane protons is insensitive to aliphatic solvents, but there is an upfield shift of the cubane protons in benzene-d6 relative to the position in carbon tetrachloride. Electron-withdrawing substi tuents and the shift reagent induce a downfield shift for the cubane proton resonances. Part II describes a reinvestigation of the photochemistry of cyclo pentadiene in an attempt to offer an explanation of the product distri bution in the sensitized irradiation. Unfortunately, sensitized and un sensitized irradiations carried out at ~600 and 00, with low and high pressure ultraviolet light sources, were too inconclusive to permit meaningful conclusions to be drawn. (I) THE EFFECT OF SOLVENT AND SHIFT REAGENTS ON THE PROTON MAGNETIC RESONANCE SPECTRA. OF SCNE CUBANE DERIVATIVES (II) ON THE MECHANISM OF PHOTODIMERIZATION OF CYCLOPENTADIENE A THESIS SUBMIYI’ED TO THE FACULTY OF ATLANTA UNIVERSITY IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE BY SIDNEY GLORIA WHITE DEPARTMENT OF CHEMISTRY ATLANTA, GEORGIA DECEMBER, 1976 iv 1 2 10 21 22 23 24 28 33 36 x1.
    [Show full text]