- Janus Cross-links in Supramolecular Networks
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Thermosets composed of cross-linked polymers demonstrate enhanced thermal, solvent, chemical, and dimensional stability as compared to their non-cross-linked counterparts. However, these often-desirable material properties typically come at the expense of reprocessability, recyclability, and healability. One solution to this challenge comes from the construction of polymers that are reversibly cross-linked. We relied on lessons from Nature to present supramolecular polymer networks comprised of cooperative Janus-faced hydrogen bonded cross-links. A triazine-based guanine-cytosine base (GCB) with two complementary faces capable of self-assembly through three hydrogen bonding sites was incorporated into poly(butyl acrylate) to create a reprocessable and recyclable network. Rheological experiments and dynamic mechanical analysis (DMA) were employed to investigate the flow behavior of copolymers with randomly distributed GCB units of varying incorporation. Our studies revealed that the cooperativity of multiple hydrogen bonding faces yields excellent network integrity evidenced by a rubbery plateau that spanned the widest temperature range yet reported for any supramolecular network. To verify that each Janus-faced motif engages in multiple cross-links, we studied the effects of local concentration of the incorporated GCB units within the polymer chain. Mechanical strength improved by colocalizing the GCB within a block copolymer morphology. This enhanced performance revealed that the number of effective cross-links in the network increased with the local concentration of hydrogen bonding units. Overall, this study demonstrates that cooperative noncovalent interactions introduced through Janus-faced hydrogen bonding moieties confers excellent network stability and predictable viscoelastic flow behavior in supramolecular networks.
- Lessard, Jacob J.,Meena, Chhuttan L.,Mondal, Swagata,Sanjayan, Gangadhar J.,Sumerlin, Brent S.
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supporting information
p. 845 - 853
(2022/01/19)
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- Triazine-Based Janus G-C Nucleobase as a Building Block for Self-Assembly, Peptide Nucleic Acids, and Smart Polymers
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This communication reports on the utility of a triazine-based self-assembling system, reminiscent of a Janus G-C nucleobase, as a building block for developing (1) supramolecular polymers, (2) peptide nucleic acids (PNAs), and (3) smart polymers. The strategically positioned self-complementary triple H-bonding arrays DDA and AAD facilitate efficient self-assembly, leading to a linear supramolecular polymer.
- Meena, Chhuttan L.,Singh, Dharmendra,Kizhakeetil, Bhavya,Prasad, Manasa,George, Malini,Tothadi, Srinu,Sanjayan, Gangadhar J.
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p. 3186 - 3195
(2021/02/16)
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- UV resonance Raman spectroscopy of the supramolecular ligand guanidiniocarbonyl indole (GCI) with 244 nm laser excitation
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Ultraviolet resonance Raman (UVRR) spectroscopy is a powerful vibrational spectroscopic technique for the label-free monitoring of molecular recognition of peptides or proteins with supramolecular ligands such as guanidiniocarbonyl pyrroles (GCPs). The use of UV laser excitation enables Raman binding studies of this class of supramolecular ligands at submillimolar concentrations in aqueous solution and provides a selective signal enhancement of the carboxylate binding site (CBS). A current limitation for the extension of this promising UVRR approach from peptides to proteins as binding partners for GCPs is the UV-excited autofluorescence from aromatic amino acids observed for laser excitation wavelengths >260 nm. These excitation wavelengths are in the electronic resonance with the GCP for achieving both a signal enhancement and the selectivity for monitoring the CBS, but the resulting UVRR spectrum overlaps with the UV-excited autofluorescence from the aromatic binding partners. This necessitates the use of a laser excitation a next generation supramolecular ligand for the recognition of carboxylates. For demonstrating the feasibility of the UVRR binding studies without an interference from the disturbing UV-excited autofluorescence, benzoic acid (BA) was chosen as an aromatic binding partner for GCI. We also present the UVRR results from the binding of GCI to the ubiquitous RGD sequence (arginylglycylaspartic acid) as a biologically relevant peptide. In the case of RGD, the more pronounced differences between the UVRR spectra of the free and complexed GCI (1:1 mixture) clearly indicate a stronger binding of GCI to RGD compared with BA. A tentative assignment of the experimentally observed changes upon molecular recognition is based on the results from density functional theory (DFT) calculations.
- Holtum, Tim,Kumar, Vikas,Schlücker, Sebastian,Sebena, Daniel,Voskuhl, Jens
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supporting information
p. 2911 - 2919
(2020/12/22)
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- Supramolecular Self-Sorting Networks using Hydrogen-Bonding Motifs
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A current objective in supramolecular chemistry is to mimic the transitions between complex self-sorted systems that represent a hallmark of regulatory function in nature. In this work, a self-sorting network, comprising linear hydrogen motifs, was created. Selecting six hydrogen-bonding motifs capable of both high-fidelity and promiscuous molecular recognition gave rise to a complex self-sorting system, which included motifs capable of both narcissistic and social self-sorting. Examination of the interactions between individual components, experimentally and computationally, provided a rationale for the product distribution during each phase of a cascade. This reasoning holds through up to five sequential additions of six building blocks, resulting in the construction of a biomimetic network in which the presence or absence of different components provides multiple unique pathways to distinct self-sorted configurations.
- Coubrough, Heather M.,van der Lubbe, Stephanie C. C.,Hetherington, Kristina,Minard, Aisling,Pask, Christopher,Howard, Mark J.,Fonseca Guerra, Célia,Wilson, Andrew J.
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supporting information
p. 785 - 795
(2019/01/04)
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- ACYLGUANIDINES FOR TREATING OSTEOARTHRITIS
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The present invention relates to compounds of the formula (I) and in particular to medicaments comprising at least one compound of the formula I for use in the treatment and/or prophylaxis of physiological and/or pathophysiological conditions in the trigg
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Paragraph 0232; 0233
(2015/12/30)
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- Axinellamines as broad-spectrum antibacterial agents: Scalable synthesis and biology
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Antibiotic-resistant bacteria present an ongoing challenge to both chemists and biologists as they seek novel compounds and modes of action to out-maneuver continually evolving resistance pathways, especially against Gram-negative strains. The dimeric pyrrole-imidazole alkaloids represent a unique marine natural product class with diverse primary biological activity and chemical architecture. This full account traces the strategy used to develop a second-generation route to key spirocycle 9, culminating in a practical synthesis of the axinellamines and enabling their discovery as broad-spectrum antibacterial agents, with promising activity against both Gram-positive and Gram-negative bacteria. While their detailed mode of antibacterial action remains unclear, the axinellamines appear to cause secondary membrane destabilization and impart an aberrant cellular morphology consistent with the inhibition of normal septum formation. This study serves as a rare example of a natural product initially reported to be devoid of biological activity surfacing as an active antibacterial agent with an intriguing mode of action.
- Rodriguez, Rodrigo A.,Barrios Steed, Danielle,Kawamata, Yu,Su, Shun,Smith, Peter A.,Steed, Tyler C.,Romesberg, Floyd E.,Baran, Phil S.
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p. 15403 - 15413
(2015/01/09)
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- INHIBITORS OF CYTOMEGALOVIRUS
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Compounds of Formula (I) wherein n, R1, R1A, R2, R3, Y and Z are defined herein, are useful for the treatment of cytomegalovirus disease and/or infection.
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Page/Page column 52
(2015/03/06)
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- Design, synthesis and binding studies of a novel quadruple ADDA hydrogen-bond array
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The design and synthesis of a novel ADDA hydrogen-bond array is described. The ureidodiimidazole motif (UDIM) 2 engages in interactions with complementary diamidonaphthyridine (DAN) 3 motifs with an association constant Ka = 825 ± 16 M-1 in chloroform. 1H NMR and molecular modelling studies were carried out in order to explain the unexpected behaviour of this new supramolecular motif. These revealed that a combination of effects including; an energetic bias for the folded conformer, subtle differences in shape complementarity between the two components and the potential for self-association of UDIM 2 disfavour higher affinity interactions between the two components.
- Pellizzaro, Maria L.,Barrett, Simon A.,Fisher, Julie,Wilson, Andrew J.
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scheme or table
p. 4899 - 4906
(2012/07/28)
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- Conformer-independent ureidoimidazole motifs-tools to probe conformational and tautomeric effects on the molecular recognition of triply hydrogen-bonded heterodimers
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Linear arrays of hydrogen bonds are useful for the reversible assembly of "stimuli-responsive" supramolecular materials. There is thus an ongoing requirement for easy-to-synthesise motifs that are capable of presenting hydrogen-bonding functionality in a
- Pellizzaro, Maria L.,McGhee, Andrea M.,Renton, Lisa C.,Nix, Michael G.,Fisher, Julie,Turnbull, W. Bruce,Wilson, Andrew J.
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scheme or table
p. 14508 - 14517
(2012/01/15)
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- Solid-state structures of ureidoimidazoles
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This work outlines the synthesis and solid-state structures of a series of ureidoimidazole derivatives. The ureidoimidazoles all adopt a common tautomeric configuration and possess remarkably consistent features of supramolecular organisation that are aff
- McGhee, Andrea M.,Plante, Jeffrey P.,Kilner, Colin A.,Wilson, Andrew J.
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experimental part
p. 470 - 479
(2012/02/01)
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- A novel synthesis of the 2-amino-1H-imidazol-4-carbaldehyde derivatives and its application to the efficient synthesis of 2-aminoimidazole alkaloids, oroidin, hymenidin, dispacamide, monobromodispacamide, and ageladine A
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A novel synthesis of 2-amino-1H-imidazol-4-carbaldehyde derivatives was achieved by the reaction of tert-butoxycarbonylguanidine with 3-bromo-1,1-dimethoxypropan-2-one as a key step. The usefulness of the derivatives as building blocks was proved by accomplishing the efficient synthesis of the representative 2-aminoimidazole alkaloids, oroidin, hymenidin, dispacamide, monobromodispacamide, and ageladine A.
- Ando, Naoki,Terashima, Shiro
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experimental part
p. 6224 - 6237
(2010/09/11)
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- Process for the preparation of substituted pyrimidine derivatives
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The present invention is directed to processes for the preparation of substituted pyrimidine derivatives, useful as intermediates in the synthesis of histamine H4 receptor modulators, and to intermediates in H4 modulator synthesis.
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Page/Page column 16
(2010/02/16)
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- Ng-acylated imidazolylpropylguanidines as potent histamine H4 receptor agonists: selectivity by variation of the n g-substituent?
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3-(1H-Imidazol-4-yl)propylguanidine (SK&F 91486, 4) was identified as a potent partial agonist at the human histamine H3 receptor (hH3R) and human histamine H4 receptor (hH4R). With the aim to increase selectivity for the
- Igel, Patrick,Schneider, Erich,Schnell, David,Elz, Sigurd,Seifert, Roland,Buschauer, Armin
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supporting information; experimental part
p. 2623 - 2627
(2010/03/24)
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- DERIVATIVES OF QUINOLINES AND QUINOXALINES AS PROTEIN TYROSINE KINASE INHIBITORS
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The invention relates to compounds of Formula (I), wherein the substituens are as defined in the specification, in free form or in the form of a pharmaceutically acceptable salt, solvate, ester, N-oxide thereof; processes for the preparation thereof; to p
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Page/Page column 176
(2009/12/27)
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- A facile and efficient multi-gram synthesis of N-protected 5-(guanidinocarbonyl)-1H-pyrrole-2-carboxylic acids
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The synthesis of two versatile building blocks for supramolecular anion binding motifs, 5-(N-Boc-guanidinocarbonyl)-1H-pyrrole-2-carboxylic acid (1) and 5-(N-Cbz-guanidinocarbonyl)-1H-pyrrole-2-carboxylic acid (2) is reported. Using these building blocks, a guanidiniocarbonyl-pyrrole anion binding site can easily be introduced into more complex molecules by using standard amide coupling conditions. Both syntheses can be performed on a multi-gram scale. The products are obtained in pure form and can be stored as solids without decomposition. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.
- Schmuck, Carsten,Bickert, Volker,Merschky, Michael,Geiger, Lars,Rupprecht, Daniel,Dudaczek, Juergen,Wich, Peter,Rehm, Thomas,Machon, Uwe
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p. 324 - 329
(2008/09/18)
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- Conformer independent heterodimerisation of linear arrays using three hydrogen bonds
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5-Membered heterocycles are employed to give a conformer independent DDA array of hydrogen bonds, resulting in enhanced binding affinity to a complementary AAD array in comparison to a DDA array employing a 6-membered ring. The Royal Society of Chemistry.
- McGhee, Andrea M.,Kilner, Colin,Wilson, Andrew J.
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p. 344 - 346
(2008/09/19)
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- Decomposition of 1-(ω-aminoalkanoyl)guanidines under alkaline conditions
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The decomposition of some NG-(ω-aminoalkanoyl)argininamides, which are key intermediates for the preparation of radiolabeled and fluorescent neuropeptide Y receptor ligands, prompted us to synthesize a small series of simple 1-(ω-aminoalkanoyl)guanidines, and to investigate these model compounds for stability in alkaline buffers. The degradation of acylguanidines was monitored by time resolved UV spectroscopy. The most labile compound, 1-(5-aminopentanoyl)guanidine, decomposed with a half life of 19 s to yield piperidin-2-one (pH 10.4 at 25 °C). In contrast the half life of 1-(6-aminohexanoyl)guanidine is 7.7 h, which is comparable to the hydrolysis of acetylguanidine (t1/2 = 9.6 h) in alkaline solution.
- Brennauer, Albert,Keller, Max,Freund, Matthias,Bernhardt, Günther,Buschauer, Armin
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p. 6996 - 6999
(2008/03/12)
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- PEPTIDOMIMETICS SELECTIVE FOR THE SOMATOSTATIN RECEPTOR SUBTYPES 1 AND/OR 4
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The invention relates to (hetero)arylsulfonylamino based peptidomimetics of formula (I), wherein A, D, E, J, Q1 R1 , R2, R3, p and j are defined as disclosed, or a pharmaceutically acceptable salt or ester thereof. Compounds of formula (I) possess high affinity and selectivity for the somatostatin receptor subtypes sst1 and/or sst4 and can be used for the treatment or diagnosis of diseases or conditions wherein sst1 and/or sst4 agonists or antagonists are indicated to be useful.
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Page/Page column 87-88
(2010/11/24)
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- Biogenetically inspired synthesis of marine C6N4 2-aminoimidazole alkaloids: Ab initio calculations, tautomerism, and reactivity
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(Chemical Equation Presented) A simple synthesis of the fused tetrahydro-imidazopyridine 13 was accomplished via selective addition of protected guanidine to N-carbomethoxy-1,2-dihydropyridine in the presence of bromine. Base-mediated semicleavage of the aminal gave 4-substituted 2-aminoimidazole 14. With this new method, natural marine metabolite 3-amino-1-(2-aminoimidazol-4-yl)-prop-1-ene (1) and derivatives may now be prepared from pyridine. Ab initio calculations of the energies of tautomers I-IV and deuteration experiments have provided insight into their reactivity.
- Abou-Jneid, Robert,Ghoulami, Said,Martin, Marie-Therese,Dau, Elise Tran Huu,Travert, Nathalie,Al-Mourabit, Ali
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p. 3933 - 3936
(2007/10/03)
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- A novel traceless resin-bound guanidinylating reagent for secondary amines to prepare N,N-disubstituted guanidines
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Matrix presented We report the development of a solid support-linked guanidinylating reagent. This reagent consists of a urethane-protected triflyl guanidine attached to the resin via a carbamate linker. It allows for rapid synthesis of guanidines from a variety of amines. It provides access to N-alkyl/aryl-or N,N-dialkylguanidines under mild conditions. Cleavage with 50% TFA produces target molecules in high yields and purity. The ability to guanidinylate secondary amines is a significant feature of this guanidinylating reagent.
- Zapf, Christoph W.,Creighton, Christopher J.,Tomioka, Mika,Goodman, Murray
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p. 1133 - 1136
(2007/10/03)
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- Guanidinylation reagents
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Trisubstituted N-protected guanidines and methods for use as guanidinylating reagents to yield N-protected guanidine derivatives.
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- Triurethane-protected guanidines and triflyldiurethane-protected guanidines: New reagents for guanidinylation reactions
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New guanidinylation reagents are reported. These reagents consist of N,N',N''-tri-Boc-guanidine (1) and N,N',N''-tri-Cbz-guanidine (2), which allow for the facile conversion of alcohols to substituted guanidines. A series of arginine analogues were synthesized via condensation of a primary or secondary alcohol with the guanidinylation reagents 1 or 2, under Mitsunobu conditions, to produce protected alkylated guanidines. In addition, an extended study of the previously reported reagents N,N'-di-Boc-N''- triflylguanidine (3) and N,N'-di-Cbz-N''-triflylguanidine (4) is presented. The triflyldiurethane-protected guanidine 3 was utilized to guanidinylate primary and secondary amines under mild conditions with high yield in both solution and on solid phase.
- Feichtinger, Konrad,Sings, Heather L.,Baker, Tracy J.,Matthews, Kenneth,Goodman, Murray
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p. 8432 - 8439
(2007/10/03)
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