Self-association of an indole based guanidinium-carboxylate-zwitterion: formation of stable dimers in solution and the solid state

Rether, Carolin; Sicking, Wilhelm; Boese, Roland; Schmuck, Carsten

doi:10.3762/bjoc.6.3

Cited by 14 publications

(13 citation statements)

References 31 publications

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“…The novel building block for GCI was synthesized in a 4-step synthesis adapted from a previous work [ 28 ] and then functionalized accordingly, yielding the GCI ethyl amide (for detailed synthesis routes, see Scheme S1 and Scheme S2 in Supporting Information File 1 ). The functionalization of the binding motifs GCP and GCI were performed since in the presence of the free guanidinium moiety the free carboxylic acid leads to a strong dimerization based on zwitterion formation at neutral pH, as described for GCP ( K dim >10 2 in water) [ 29 ] as well as for a GCI derivative [ 30 ], which would interfere with the anion binding. Solid benzoic acid and RGD were purchased from Fluka Analytical and Sigma-Aldrich, respectively.…”

Section: Methodsmentioning

confidence: 99%

UV resonance Raman spectroscopy of the supramolecular ligand guanidiniocarbonyl indole (GCI) with 244 nm laser excitation

Holtum

Kumar

Sebena

et al. 2020

Beilstein J. Org. Chem.

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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 <260 nm for spectrally separating the UVRR spectrum of the supramolecular ligand from the UV-excited autofluorescence of the peptide or protein. Here, we demonstrate the use of UVRR spectroscopy with 244 nm laser excitation for the characterization of GCP as well as guanidiniocarbonyl indole (GCI), 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.

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Section: Methodsmentioning

confidence: 99%

UV resonance Raman spectroscopy of the supramolecular ligand guanidiniocarbonyl indole (GCI) with 244 nm laser excitation

Holtum

Kumar

Sebena

et al. 2020

Beilstein J. Org. Chem.

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“…We used a series of knock-out analogues ( Figure 18) to evaluate the importance of individual interactions, such as the charges, the H-bond pattern, the size and geometry of the aromatic ring, or the acidity and electronic properties of Figure 17 Dimerization of the guanidiniocarbonyl pyrrole carboxylate zwitterion to form very stable dimers held together by hydrogenbond enforced ion pairs, even in aqueous solvents; the solid state structure (bottom left) as well as the calculated electrostatic surface potential (bottom right) underline the perfect self-complementarity of the zwitterion the guanidinium moiety. The experimental data 50,54 were backed up by high-level DFT calculations. 51 Over time, a consistent picture emerged: (a) the charge interaction is crucial, (b) the charge interaction is significantly re-enforced by the H-bond pattern, (c) the inner H-bonds (less solvent exposed) are more important than the outer ones, and (d) the pK a of the guanidinium cation also affects stability: the more acidic, the more stable the ion pair.…”

Section: Self-assembling Zwitterionsmentioning

confidence: 99%

“…We used a series of knock-out analogues (Figure 18) to evaluate the importance of individual interactions, such as the charges, the H-bond pattern, the size and geometry of the aromatic ring, or the acidity and electronic properties of the guanidinium moiety. The experimental data 50,54 were backed up by high-level DFT calculations. 51 Over time, a consistent picture emerged: (a) the charge interaction is crucial, (b) the charge interaction is significantly re-enforced by the H-bond pattern, (c) the inner H-bonds (less solvent exposed) are more important than the outer ones, and (d) the pK a of the guanidinium cation also affects stability: the more acidic, the more stable the ion pair.…”

Section: Nucleic Acids As Targetsmentioning

confidence: 99%

A Journey through 12 Years of Interacting Molecules: From Artificial Amino Acid Receptors to the Recognition of Biomolecules and Switchable [nl]Nanomaterials

Schmuck¹

2011

Synlett

Self Cite

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A J o u r n e y t h r o u g h 1 2 Y e a r s o f I n t e r a c t i n g M o l e c u l e s Abstract: Research in supramolecular chemistry has been carried out in my laboratory for the past 12 years. Intrigued by the fascinating power of supramolecular chemistry, as seen in biomolecular recognition events in nature, we started out by trying to mimic the basic principles of such recognition events in small artificial model systems. Our first targets were amino acids and oligopeptides. We then moved on to proteins and nucleic acids, and we started to develop supramolecular systems that, besides simple binding, also featured functions, e.g. shutting down enzymes or allowing gene delivery into cells. In recent years and in a completely different yet related field, we have begun to develop self-assembling nanomaterials. The basic idea for this derived from an accidental discovery of the interesting self-assembling properties of a simple zwitterion, which was a synthetic intermediate on the route to our amino acid receptors. This personal account summarizes this journey and is intended not only to present the most-important findings from our laboratory so far, but also to shed light on how all these projects developed over the years and how our journey took us to where we are now.

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“…In comparison with corresponding benzoylthioureas, N 1 , N 3 ‐disubstituted benzoylguanidines are expected to work better as sensors due to larger number of protons available for hydrogen bonding especially if protonated. Like benzoylthioureas, aroylguanidines possess co‐planar substructure due to intramolecular hydrogen bonding and larger orbital overlap between aroyl chromophore and guanidine moiety.…”

Section: Introductionmentioning

confidence: 99%

Benzoylguanidines as Anion‐Responsive Systems

et al. 2018

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A series of benzoylguanidinium salts was prepared and the changes in UV/Vis spectra, triggered by the presence of anions, were investigated. All compounds undergo deprotonation with basic anions like dihydrogenphosphate and acetate in acetonitrile. The most pronounced spectral changes were obtained by deprotonation of N1‐benzoyl‐N3‐(p‐nitrophenyl) guanidinium chloride which shows the naked‐eye visible color change from colorless to yellow. Measured pKa(BH+) in acetonitrile ranges from 12–16, which is comparable to the pyridinium cations. The proton transfer equilibria were also tested in acetonitrile/water mixture where all but the most acidic derivatives showed pKa(BH+) of 4–6 units which corresponds to apparent association constants of 104–106 dm3 mol−1. UV/Vis spectra of neutral and protonated forms were modelled by the TD‐DFT approach using CAM‐B3LYP and PBE0 functionals and compared to CC2 results. In the case of CAM‐B3LYP, a parameter ω, defining amount of long‐range exchange correction, was varied to achieve the best agreement with the experimental spectra. The optimized ω parameters are 0.10 a0−1 for neutral benzoylguanidines and 0.20 a0−1 for neutral nitrobenzoyl and protonated systems. The larger ω parameter in the latter is ascribed to more pronounced charge transfer character of the HOMO‐LUMO transition – the one responsible for the lowest energy absorption band.

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Self-association of an indole based guanidinium-carboxylate-zwitterion: formation of stable dimers in solution and the solid state

Cited by 14 publications

References 31 publications

UV resonance Raman spectroscopy of the supramolecular ligand guanidiniocarbonyl indole (GCI) with 244 nm laser excitation

UV resonance Raman spectroscopy of the supramolecular ligand guanidiniocarbonyl indole (GCI) with 244 nm laser excitation

A Journey through 12 Years of Interacting Molecules: From Artificial Amino Acid Receptors to the Recognition of Biomolecules and Switchable [nl]Nanomaterials

Benzoylguanidines as Anion‐Responsive Systems

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