DOCSLIB.ORG

Host-Guest Chemistry Between Cucurbit[7]Uril and Neutral and Cationic Guests

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Host-Guest Chemistry Between Cucurbit[7]Uril and Neutral and Cationic Guests HOST-GUEST CHEMISTRY BETWEEN CUCURBIT[7]URIL AND NEUTRAL AND CATIONIC GUESTS by Ian William Wyman A thesis submitted to the Department of Chemistry In conformity with the requirements for the degree of Doctor of Philosophy. Queen’s University Kingston, Ontario, Canada (January, 2010) Copyright © Ian William Wyman, 2010 Dedicated in memory of my Grandfather, Norman Brannen, 1917-2009. ii Abstract This thesis describes the host-guest chemistry between cucurbit[7]uril (CB[7]) and various series of guests, including neutral polar organic solvents, bis(pyridinium)alkane dications, local anaesthetics, acetylcholine analogues, as well as succinylcholine and decamethonium analogues, in aqueous solution. A focus of this thesis is the effects of varying the chemical structures within different series of guests upon the nature of the host-guest chemistry, such as the relative position and orientation of the guest relative to the CB[7] cavity, and the strengths of the binding affinities. The binding affinities of polar organic solvents with CB[7] depend upon the hydrophobic effect and dipole-quadrupole interactions. The polar guests align themselves so that their dipole moment is perpendicular to the quadrupole moment of CB[7]. The binding strengths of acetone and acetophenone to CB[7] decrease in the presence of alkali metals. Discrete 1:1 and 2:1 host-guest complexes are formed between CB[7] and a series of α,ω -bis(pyridinium)alkane guests. In most cases the CB[7] initially occupies the aliphatic linker when the 1:1 complex is formed and migrates to the terminal regions as the second CB[7] is added. When bulky, hydrophobic tert -butyl substituents are present, however, the CB[7] occupies the terminal pyridinium region and not the central linker. Supramolecular complexes between CB[7] and a series of local anaesthetics have binding affinities 2-3 orders of magnitude greater than reported values with β-cyclodextrin. The first p Ka values of the guests increase by 0.5-1.9 units upon complexation. The binding positions of the guests within CB[7] differ in neutral and acidic media, with the systems thus behaving as pH- activated switches. iii With supramolecular complexes between CB[7] and various cationic cholines and their phosphonium analogues, the CB[7] cavity is occupied by the charge-diffuse cationic region. The binding affinities and positions vary depending on the nature of the onium group as well as the substituents within the guest molecule. Host-guest complexes between CB[7] and dicationic acetylcholinesterase inhibitors have 1:1 binding affinities between 8 x 10 6 and 3 x 10 10 M -1, with 2:1 binding being significantly weaker. These binding affinities are related to the nature of the cationic onium groups, and the length and hydrophobicity of the connecting linkers. iv Acknowledgements I would like to take this opportunity, first and foremost, to thank my supervisor, Dr. Donal Macartney, for his kindness, help, guidance, and patience during my studies. It has been a pleasure studying in his research group. I would also like to thank Dr. Francoise Sauriol for her kindness, helpful discussions, regarding NMR characterizations, and her assistance and training with the instrumentation. In addition, I would like to thank the members of the mass spectrometry facility, which have included Bernd Keller, Jie (Jessie) Sui, Lina Yuan, and Jiaxi Wang for their helpful advice, and for running the high-resolution samples. I wish to also thank the faculty members of the Department of Chemistry for their guidance, excellent teaching and research advice, and also the staff of both the department and Queen’s University. I would like to take this opportunity to thank members of the chemistry office, especially Annette Keyes, for her helpfulness with scholarship and fellowship applications. I also want to thank Lyndsay Hull for loaning chemicals and equipment during the course of my studies here. It has been a pleasure working with members of the Macartney lab, both past and present, including Ruibing Wang, Lina Yuan, Saroja Hettiarachchi, Andrew Fraser, Mona Gamal Eldin, Brendan MacGillivray, Julian Kwok, Antony St-Jacques, Priscilla Leung, and Andrew Carrier. I thank them for their friendship and helpful discussions. I would like to especially take this opportunity to thank my parents, Bill and Diane Wyman, for their love, encouragement, and support. v In addition, I greatly appreciate the financial assistance that has been provided by the Ontario Ministry of Training, Colleges and Universities though the OGS program, as well as to the Walter C. Sumner Foundation, for its support. vi Statement of Originality I hereby certify that all of the work described within this thesis is the original work of the author. Any published (or unpublished) ideas and/or techniques from the work of others are fully acknowledged in accordance with the standard referencing practices. Ian William Wyman January, 2010 vii Table of Contents Abstract .......................................................................................................................................... iii Acknowledgements ..........................................................................................................................v Statement of Originality................................................................................................................ vii Table of Contents ......................................................................................................................... viii List of Figures ............................................................................................................................... xii List of Abbreviations.................................................................................................................. xviii Chapter 1 Introduction .....................................................................................................................1 1.1 Non-covalent interactions ......................................................................................................1 1.1.1 Hydrogen Bonding ..........................................................................................................2 1.1.2 Van der Waals Interactions .............................................................................................3 1.1.3 The Hydrophobic Effect..................................................................................................4 1.1.4 π−π Stacking Interactions ...............................................................................................6 1.1.5 Electrostatic Interactions .................................................................................................8 1.2 Concepts of Supramolecular Chemistry: Molecular Recognition and Self-Assembly, Macrocyclic Hosts, Rotaxanes, and Catenanes....................................................................10 1.2.1 Self-Assembly and Molecular Recognition...................................................................11 1.2.2 Macrocyclic Hosts.........................................................................................................12 1.2.3 Supramolecular Complexes involving Macrocyclic Hosts: Rotaxanes and Catenanes................................................................................................................13 1.3 Supramolecular Characterization .........................................................................................15 1.3.1 Nuclear Magnetic Resonance (NMR) Spectroscopy.....................................................16 1.3.2 UV-visible Spectroscopy...............................................................................................18 1.3.3 X-ray Crystallography...................................................................................................18 1.3.4 Mass Spectrometry........................................................................................................19 1.3.5 Determination of Binding Constants.............................................................................20 1.4 Non-Cucurbituril Macrocyclic Hosts ...................................................................................23 1.4.1 Crown Ethers.................................................................................................................23 1.4.2 Calixarene Hosts ...........................................................................................................27 1.4.3 Porphyrin Hosts.............................................................................................................35 1.4.4 Cyclodextrins ................................................................................................................38 viii 1.5 Cucurbituril Hosts ................................................................................................................42 1.5.1 Cucurbit[6]uril (CB[6]) .................................................................................................46 1.5.2 Cucurbit[5]uril (CB[5]) .................................................................................................56 1.5.3 Cucurbit[7]uril (CB[7]) .................................................................................................59 1.5.4 Cucurbit[8]uril (CB[8]) .................................................................................................65 1.5.5 Cucurbit[10]uril (CB[10]) .............................................................................................71
Load more

Recommended publications
  • Cucurbituril Assembly and Uses Thereof Cucurbiturilanordnung Und Seine Verwendungen Ensemble De Cucurbituril Et Ses Utilisations
    (19) TZZ_Z__T (11) EP 1 668 015 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: C07D 487/22 (2006.01) C07D 519/00 (2006.01) of the grant of the patent: G01N 33/00 (2006.01) C08G 73/00 (2006.01) 21.08.2013 Bulletin 2013/34 (86) International application number: (21) Application number: 04770467.1 PCT/IL2004/000796 (22) Date of filing: 05.09.2004 (87) International publication number: WO 2005/023816 (17.03.2005 Gazette 2005/11) (54) CUCURBITURIL ASSEMBLY AND USES THEREOF CUCURBITURILANORDNUNG UND SEINE VERWENDUNGEN ENSEMBLE DE CUCURBITURIL ET SES UTILISATIONS (84) Designated Contracting States: (56) References cited: AT BE BG CH CY CZ DE DK EE ES FI FR GB GR WO-A-00/68232 WO-A-03/004500 HU IE IT LI LU MC NL PL PT RO SE SI SK TR WO-A-03/055888 WO-A-03/055888 (30) Priority: 04.09.2003 US 499735 P • JON, SANG YONG ET AL: "Facile Synthesis of 13.01.2004 US 535829 P Cucurbit[n]uril Derivatives via Direct Functionalization: Expanding Utilization of (43) Date of publication of application: Cucurbit[n]uril" JOURNAL OF THE AMERICAN 14.06.2006 Bulletin 2006/24 CHEMICAL SOCIETY , 125(34), 10186-10187 CODEN: JACSAT; ISSN: 0002-7863, 8 June 2003 (73) Proprietor: TECHNION RESEARCH AND (2003-06-08), XP002316247 DEVELOPMENT FOUNDATION, LTD. • JON, SANG YONG ET AL: "Facile Synthesis of Haifa 32000 (IL) Cucurbit[n]uril Derivatives via Direct Functionalization: Expanding Utilization of (72) Inventor: KEINAN, Ehud Cucurbit[n]uril" JOURNAL OF THE AMERICAN 23 840 Timrat (IL) CHEMICAL SOCIETY , 125(34), 10186-10187 CODEN: JACSAT; ISSN: 0002-7863, 2003, (74) Representative: Dennemeyer & Associates S.A.
    [Show full text]
  • Study on the Complexation of Macromolecule Cucurbituril with Metals and Acetamide
    International Journal of Chemistry and Applications. ISSN 0974-3111 Volume 4, Number 3 (2012), pp. 219-226 © International Research Publication House http://www.irphouse.com Study on the Complexation of Macromolecule Cucurbituril with Metals and Acetamide T. Jaba Priya, Jasmine Rebecca and R. Wilfred Sugumar Department of Chemistry, Madras Christian College (Autonomous), Tambaram, Chennai-600059, India. E-mail: [email protected]; [email protected] Abstract Cucurbituril is a remarkably robust macro cyclic host molecule that has a rigid cavity capable of binding small guests under a variety of conditions. In the present study, macromolecule cucurbit[6]uril (CB[6]) and its complexes with metal ions lithium, cerium were synthesized. Mixed ligand complexes containing CB[6] and acetamide with central metal ions such as lithium were also prepared. The UV – visible spectrum of the complex of lithium with CB[6] shows a peak at 225nm. The mixed ligand complex of lithium with CB[6] and acetamide shows a sharp peak at 220nm which indicates the presence of amide functional group. The peak at 274nm indicates the presence of – NO2 group. UV-visible spectrum of the complex of cerium with CB[6] shows a peak at 213.17nm, which indicates the presence of – CONH2 group. The IR spectrum of Cucurbituril shows the following peaks 3436.96 cm-1 , 2931.16 to 2372.15 cm-1 and a sharp peak at 1726.39 cm-1 these frequencies indicate the presence of CO - N ,C-H and C=O stretching respectively. The IR spectra of the complex of Lithium with CB[6] and Cerium with CB[6] show significant variations especially around 3000 cm-1 and between 1700 to 1200 cm-1 indicating prevalence of enhanced hydrogen bonding.
    [Show full text]
  • Cucurbit[7]Uril Host-Viologen Guest Complexes
    CUCURBIT[7]URIL HOST-VIOLOGEN GUEST COMPLEXES: ELECTROCHROMIC AND PHOTOCHEMICAL PROPERTIES by MARINA FREITAG A dissertation submitted to the Graduate School – Newark Rutgers, The State University of New Jersey in partial fulfillment of requirements for the degree of Doctor of Philosophy Graduate Program in Chemistry Written under the direction of Professor Elena Galoppini and approved by ________________________ ________________________ ________________________ ________________________ Newark, New Jersey October, 2011 ABSTRACT OF THE DISSERTATION Abstract Cucurbituril[7] Host - Viologen Guest Complexes: Electrochromic and Photochemical Properties By MARINA FREITAG Dissertation Director: Professor Elena Galoppini In this thesis, we demonstrated that a molecular host, cucurbit[7]uril, provides an alternative method of adsorbing molecules on semiconductors and shields the guest from the hetereogenous interface. These novel hybrid systems exhibited photophysical and electrochemical properties that differ from the properties of layers obtained by directly attaching the chromophore to the semiconductor through binding groups. This thesis describes the host-guest chemistry between cucurbit[7]uril (CB[7]) and various series of viologen guests. Methylviologen (1,1'-dimethyl-4,4'-bipyridinium dichloride, MV2+), 1-methyl-1'-p-tolyl-4,4'-bipyridinium dichloride (MTV2+), and 1,1'-di- p-tolyl-(4,4'-bipyridine)-1,1'-diium dichloride (DTV2+) were encapsulated in the macrocyclic host cucurbit[7]uril, CB[7]. The complexes MV2+@CB[7] and MTV2+@CB[7] were physisorbed to the surface of 1 TiO2 nanoparticle films. The complexation into CB[7] was monitored by H NMR. TiO2 films functionalized with the complexes were studied by FT-IR-ATR and UV-Vis ii absorption. The electrochemical and spectroelectrochemical properties of MV2+@CB[7] and MTV2+@CB[7] were studied in solution and in electrochromic windows (ECDs), where the complexes were bound to TiO2 films cast on FTO.
    [Show full text]
  • Formation of Functionalized Supramolecular Metallo-Organic Oligomers with Cucurbituril a Thesis Presented to the Faculty Of
    Formation of Functionalized Supramolecular Metallo-organic Oligomers with Cucurbituril A thesis presented to the faculty of the College of Arts and Sciences of Ohio University In partial fulfillment of the requirements for the degree Master of Science Ian M. Del Valle December 2015 © 2015 Ian M. Del Valle. All Rights Reserved. 2 This thesis titled Formation of Functionalized Supramolecular Metallo-organic Oligomers with Cucurbituril by IAN M. DEL VALLE has been approved for the Department of Chemistry and Biochemistry and the College of Arts and Sciences by Eric Masson Associate Professor of Chemistry and Biochemistry Robert Frank Dean, College of Arts and Sciences 3 Abstract DEL VALLE, IAN M., M.S., December 2015, Chemistry Formation of Functionalized Supramolecular Metallo-organic Oligomers with Cucurbituril Director of Thesis: Eric Masson The goal of this project is to functionalize supramolecular oligomer chains with amino acids and nucleic acids in order to observe interactions with proteins and DNA. Chiral substituents are also desirable to induce helicality in the oligomer much like DNA. We explored different pathways to afford these oligomers. The first project involves forming metallo-organic oligomers using non-covalent bonds and then functionalizing them. We synthesize ligands and use alkyne-azide cycloadditions to functionalize them. These ligands can then be coordinated to various transition metals. The aromatic regions of these oligomers can then self-assemble into tube-like chains with the participation of cucurbit[8]uril. Second, we explore an alternate pathway to form functionalized chains. This second set of chains coupled amines with carboxylic acid groups attached to the ligands. This project hopes to avoid solubility problems experienced with the first project.
    [Show full text]
  • Synthesis and Characterization of Supramolecular Cucurbituril, Molybdenum 2,2'-Bipyridyl Complex
    International Journal of Scientific & Engineering Research Volume 8, Issue 10, October-2017 140 ISSN 2229-5518 SYNTHESIS AND CHARACTERIZATION OF SUPRAMOLECULAR CUCURBITURIL, MOLYBDENUM 2,2’-BIPYRIDYL COMPLEX Ms. Anitha. V1 , Dr. Nandagopal. J2, Ms. Ramanachiar.R3, Ms. Sasikala.S4, Ms. Ariyamala .R5 Department of chemistry, Velammal Engineering college, Chennai, Tamilnadu. Abstract Supra molecular Cucurbituril, Molybdenum2,2’-bipyridyl complex has been synthesized by precipitation followed by slow evaporation techniques. Changes in the physical properties of the ligand and the complex were characterized by melting point and solubility test . The absorption spectrum of the Cucurbituril, Molybdenum2,2’-bipyridyl complex were studied by decreasing and increasing concentrations by using UV – Visible spectrophotometer and IR spectrophotometer. The interaction between the metal and ligands were studied by UV- visible spectral analysis. The functional groups and modes of vibration were identified by IR spectral analysis. Key words: Cucurbituril, evaporation, precipitation, absorption, ligand, spectrophotometer. INTRODUCTION complex of Cucurbit[6]uril which incorporates the p-Xylene diammonium cation into the macrocyclic A Supramolecular assembly or “supramolecule” is a cavity. Researchers have shown that Cucurbit[6]uril well defined complex of molecules held together by acts as a catalyst in cyclo-addition reactions. noncovalent bonds. Cucurbiturils are macrocyclic Detailed examination has been done on the molecules consisting of glycouril repeating units. construction of supramolecular organic, inorganic These supramolecular compounds are particularly compounds from macrocyclic cavitand interesting to chemists because they are molecular cucurbit[6]Uril and mono and polynuclear aqua containers that are capable of binding other complexes. Cucurbit[6]uril is used in the molecules within their cavities.
    [Show full text]
  • Host-Guest Compounds Oligomeric Cucurbituril Complexes: from Peculiar Assemblies to Emerging Applications Xue Yang, Ruibing Wang, Anthony Kermagoret, David Bardelang
    Host-Guest Compounds Oligomeric Cucurbituril Complexes: from Peculiar Assemblies to Emerging Applications Xue Yang, Ruibing Wang, Anthony Kermagoret, David Bardelang To cite this version: Xue Yang, Ruibing Wang, Anthony Kermagoret, David Bardelang. Host-Guest Compounds Oligomeric Cucurbituril Complexes: from Peculiar Assemblies to Emerging Applications. Ange- wandte Chemie International Edition, Wiley-VCH Verlag, 2020, pp.2-15. 10.1002/anie.202004622. hal-02972332 HAL Id: hal-02972332 https://hal-amu.archives-ouvertes.fr/hal-02972332 Submitted on 23 Oct 2020 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Oligomeric Cucurbituril Complexes: from Peculiar Assemblies to Emerging Applications. Xue Yang,[a] Ruibing Wang,*[b] Anthony Kermagoret,*[a] and David Bardelang*[a] Abstract: Proteins are an endless source of inspiration. By carefully Xue Yang earned her Master’s degree from tuning the amino-acid sequence of proteins, nature made them evolve the University of Macau (China) in 2017. She from primary to quaternary structures, a property specific to protein is currently pursuing her PhD on the oligomers and often crucial to accomplish their function. On the other supramolecular chemistry of cucurbiturils at Aix- hand, the synthetic macrocycles cucurbiturils (CBs) have shown Marseille University.
    [Show full text]
  • Cucurbiturils As Molecular Containers: the Mechanism Of
    Cucurbiturils as Molecular Containers: The Mechanism of Complexation of Small Guests, the Effects of the Inclusion on their Photophysical Properties, and Potential Applications A thesis presented by César Augusto Márquez González to the School of Engineering and Science in fulfillment of the requirements for the degree of Doctor of Chemistry in the graduate program of Nanomolecular Sciences International University Bremen Bremen, 2003 Approved by the School of Engineering and Science by request of Prof. Dr. Hans-Jürgen Buschmann, Prof. Dr. Ulrich Kortz, Prof. Dr. Werner M. Nau, Prof. Dr. Thomas Nugent, and Prof. Dr. Ryan M. Richards Bremen, 17 December, 2003 Prof. Dr. Gerhard Haerendel Dean 2 Contents 1. Introduction 11 1.1. Supramolecular Chemistry 11 1.2. Cucurbiturils as Molecular Containers 16 1.3. Scope of Dissertation 22 2. Complexation Mechanism 26 2.1. Two Mechanisms of Slow Host-Guest Complexation between Cucurbit[6]uril and Cyclohexylmethylamine: pH-Responsive Supramolecular Kinetics 26 2.2. The Mechanism of Host-Guest Complexation by Cucurbit[6]uril 29 3. Fluorescent Host-Guest Systems 31 3.1. 2,3-Diazabicyclo[2.2.2]oct-2-ene in Supramolecular Chemistry 31 3.2. Polarizabilities Inside Molecular Containers 34 4. Potential Applications 37 4.1. Selective Fluorescence Quenching of 2,3-Diazabicyclo[2.2.2]oct-2-ene by Nucleotides 37 4.2. Cucurbiturils: Molecular Nanocapsules for Time-Resolved Fluorescence- based Assays 40 3 5. Ongoing Projects 44 5.1. The Cucurbit[7]uril•2,3-Diazabicyclo[2.2.2]oct-2-ene Host-Guest System. Influence of Associated Metal Ions on its Photophysical Properties 45 5.2.
    [Show full text]
  • Cucurbituril by Fabio Pichierri Tohoku University Sendai, Japan
    Cucurbituril by Fabio Pichierri Tohoku University Sendai, Japan Molecule of the Month - March 2006 Also available: Chime Enhanced, JMol, and VRML versions of this page. Cucurbituril (from cucurbita = pumpkin) is the fancy name given to the pumpkin-shaped macrocycle hexamer obtained from the condensation reaction between glycoluril and formaldehyde (in excess): The story of cucurbituril, hereafter referred to as CB or CB[6], starts in 1905 (Einstein's magic year!!!) when three German chemists, Behrend, Meyer, and Rusche, published a paper on the illustrious Liebigs Annalen der Chemie 339 (1905) 1. Their paper described the reaction between glycoluril and an excess of formaldehyde (see the above Scheme) which yielded a cross-linked polymer (Behrend's polymer) that upon treatment with concentrated sulfuric acid produced a crystalline precipitate. Behrend characterized the crystalline precipitate as C10H11N7O4x2H2O. At that time, however, chemists could not make use of analytical techniques such as x-ray crystallography that are nowadays routinely employed to identify the atomic structure of molecules (note that in 1912, seven years later the publication of Behrend's paper, Max von Laue observed the first diffraction pattern from crystals). The molecular structure of CB remained unknown for about 76 years up until 1981 when a team of three American chemists working at the University of Illinois, Chicago, decided to repeat the 1905 synthesis of Behrend et al. Treatment of the precipitate (Behrend's polymer) with H2SO4 (conc.) and subsequent dissolution in hot water afforded a crystalline solid which, after being subjected to a single-crystal x-ray structure analysis, revealed the beautiful pumpkin-shaped molecule shown in Figure 1.
    [Show full text]
  • Host-Guest Complexes of Cucurbit[7]Uril with Cationic Drugs
    HOST-GUEST COMPLEXES OF CUCURBIT[7]URIL WITH CATIONIC DRUGS AND AMINO ACID DERIVATIVES by Mona A. Gamal-Eldin A thesis submitted to the Department of Chemistry In conformity with the requirements for the degree of Doctor of Philosophy Queen’s University Kingston, Ontario, Canada September 2013 Copyright © Mona A. Gamal-Eldin, 2013 Abstract The host-guest chemistry between cucurbit[7]uril (CB[7]) and cationic organic guests of medicinal and biological interest are described in this thesis. In the first part, three cationic steroidal neuromuscular blockers (SNMBs) were studied, along with guests that model their monocationic N-alkyl-N-methylheterocyclic (morpholinium, pyrrolidinium and piperidinium) terminal groups of the SNMBs, and dicationic guests in which the two N-methylheterocyclic rings are linked by a decamethylene chain, modelling a variety of NMBs. Other cationic drugs related to acetylcholine processes in neuromuscular blockage were also studied. In the second part, the amino acids lysine, and its mono-, di- and trimethylated and acetylated N derivatives, and arginine, and mono- and (symmetric and asymmetric) dimethylarginine, were investigated as guests, along with analogs of arginine. The nature and strength of the complexation between CB[7] and these guests in aqueous solution were determined by 1H NMR spectroscopy and ESI mass spectrometry. 6 9 -1 The CB[7] showed high binding affinity (KCB[7] = 10 -10 M ) towards the N-alkyl-N- methylheterocyclic cations with a trend of piperidinium > pyrrolidinium > morpholinium, which reflects the relative hydrophobicities of the guests. The CB[7] forms 1:1 and 2:1 host-guest complexes with dicationic model guests, with the CB[7] initially encapsulating the decamethylene chain.
    [Show full text]
  • The State-Of-Play and Future of Platinum Drugs
    M G Apps et al. The state-of-play and future of 22:4 R219–R233 Review platinum drugs The state-of-play and future of platinum drugs Correspondence Michael G Apps, Eugene H Y Choi and Nial J Wheate should be addressed to N J Wheate Faculty of Pharmacy, The University of Sydney, Sydney, New South Wales 2006, Australia Email [email protected] Abstract The year 2015 marks the 50th anniversary since the discovery of the anticancer potential of Key Words cisplatin and it remains just as useful now as it did back then, especially for the treatment of " cancer some endocrine-related cancers like ovarian and testicular carcinomas. Since its discovery, " cisplatin five other platin drugs have received approval in various countries. While several new platin " formulation drugs are in preclinical development, in the last decade only two new platin drugs have " drug delivery entered clinical trials, LA-12 and dicycloplatin, reflecting a shift in research focus from new " functional genomics drug design to improved formulations of already approved platin drugs. These formulations include their encapsulation with macrocycles to slow and prevent their degradation by proteins and peptides; their attachment to nanoparticles to passively target solid tumours through the enhanced permeability and retention effect and their coordination to important nutrients, proteins, antibodies and aptamers for active tumour targeting. These formulation methods have all shown potential but none have yet yielded a new marketable medicine containing a platin drug. The reasons for this are problems of Endocrine-Related Cancer consistent drug loading, controlling the location and timing of drug release and the inherent toxicity of some of the drug delivery vehicles.
    [Show full text]
  • Synthetic Receptors for the Recognition and Discrimination of Post-Translationally Methylated Lysines
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by University of Lincoln Institutional Repository Synthetic receptors for the recognition and discrimination of post-translationally methylated lysines Dr. Tobias Gruber* School of Pharmacy, University of Lincoln, Joseph Banks Laboratories, Green Lane, Lincoln LN6 7DL, United Kingdom. *E-mail: [email protected] 1 Synthetic receptors for the recognition and discrimination of post-translationally methylated lysines Dr. Tobias Gruber, University of Lincoln Photo: Tobias Gruber; 50.495 N, 11.467 O 2 Abstract Post-translational modifications (PTMs) describe the chemical alteration of proteins after their biosynthesis in ribosomes. PTMs play important roles in cell biology including the regulation of gene expression, cell-cell interactions and the development of different diseases. A prominent class of PTMs is the side chain methylation of lysine. For the analysis and discrimination of differently methylated lysines antibodies are widely used, though, methylated peptide and protein targets are known to be particularly difficult to be differentiated by antibody-based affinity reagents; an additional challenge can be batch-to-batch reproducibility. The application of mass spectrometry techniques for methyllysine discrimination requires a complex sample preparation and is not suited for working in cells. The desire to overcome above-named challenges promoted the development of synthetic receptor molecules that recognize and bind methyllysines. Such ‘artificial antibodies’ are of interest for a number of applications, e.g. as reagents in biochemical assays, for the isolation and purification of post- translationally methylated proteins and for the tracking of signalling pathways. Moreover, they offer new approaches in diagnostics and therapy.
    [Show full text]
  • A Study of the Interaction Between Cucurbit[7]Uril and Alkyl Substituted 4-Pyrrolidinopyridinium Salts
    Article A Study of the Interaction between Cucurbit[7]uril and Alkyl Substituted 4-Pyrrolidinopyridinium Salts Weitao Xu 1, Xinyi Zhu 1, Bing Bian 2, Xin Xiao 1,*, Zhu Tao 1 and Carl Redshaw 3,* 1 Key Laboratory of Macrocyclic and Supramolecular Chemistry of Guizhou Province, Guizhou University, Guiyang 550025, China; [email protected] (W.X.); [email protected] (X.Z.); [email protected] (Z.T.) 2 College of Chemistry and Environmental Engineering, Shandong University of Science and Technology, Qingdao 266590, China; [email protected] 3 Department of Chemistry & Biochemistry, University of Hull, Hull HU6 7RX, UK * Correspondence: [email protected] (X.X.); [email protected] (C.R.); Tel.: +86-155-1908-9928 (X.X.); +44-148-246-5219 (C.R.) Received: 28 February 2020; Accepted: 8 April 2020; Published: 14 April 2020 Abstract: The interaction between cucurbit[7]uril (Q[7]) and a series of 4-pyrrolidinopyridinium salts bearing aliphatic substituents at the pyridinium nitrogen, namely 4-(C4H8N)C5H5NRBr, where R = H (C0), Et (C2), n-butyl (C4), n-hexyl (C6), has been studied in aqueous solution by 1H NMR spectroscopy, electronic absorption spectroscopy, and mass spectrometry. Keywords: host–guest interaction; cucurbit[7]uril; 4-pyrrolidinopyridinium 1. Introduction The behavior of a host toward a guest is typically controlled by non-covalent interactions, and this can impact greatly on the properties exhibited by the guest [1–3]. Given this, supramolecular approaches have been used extensively to construct functional materials, and these have seen applications in a number of areas, for example, in molecular electronics, drug-delivery, optical sensors, and for molecular machines [4–8].
    [Show full text]