Hydrogen-bond basicity of thioamides and thioureas

Laurence, Christian; Berthelot, M.; Questel, Jean‐Yves Le; Ghomari, Mohamed J. El

doi:10.1039/p29950002075

Cited by 49 publications

(33 citation statements)

References 18 publications

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“…Ϫ Ascaridole (38) and MeOCH(CF 3 ) 2 (20) have been generously given to us by D. G. Morris (Glasgow) and M. H. Abraham (London), respectively. Di-tert-butyl ether (8) was synthesized in the laboratory of Prof. C. Reichardt (Marburg) according to the method of Erickson and Ashton [28] . Diadamantyloxirane 21 and diadamantyldioxetane 39 have been synthetized by J.-Y.…”

Section: Methodsmentioning

confidence: 99%

“…The building of the pK HB scale contributes not only to the increasing efforts towards a quantitative description of the hydrogen bond, but also to the difficult and unachieved task of measuring quantitatively the strength of organic Lewis bases. We have already measured pK HB for nitrogen [7] , oxygen, sulfur [8] , and π [9] bases. In the case of oxygen bases, alcohols [10] , esters [11] , amides [12] , ketones [13] , nitro bases [14] , sulfonyl bases [15] , and amidates [16] have already Eur.…”

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confidence: 99%

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The Hydrogen-Bond Basicity pKHB Scale of Peroxides and Ethers

1998

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Using 4‐fluorophenol as a reference hydrogen‐bond donor, equilibrium constants, Kf, for the formation of 1:1 hydrogen‐bonded complexes have been obtained by FTIR spectrometry for 39 ethers of widely different structure (cyclic and acyclic ethers, crown ethers, glymes, acetals, orthoesters, and disiloxane) and 3 peroxides, in CCl4 at 298 K. The pKHB scale of monoethers extends from 1.44 for 2,3‐diadamant‐2‐yloxirane to –0.53 for hexamethyldisiloxane. The main effects explaining the variation of the hydrogen‐bond basicity of sp3 oxygen atoms are (i) the electron‐withdrawing field‐inductive effect [e.g. in (CF3)2CHOMe], (ii) the electron‐withdrawing resonance effect (e.g. in EtOCH=CH2) (iii) the steric effect (e.g. in tBu2O), (iv) the lone‐pair–lone‐pair repulsion (e.g. in cyclic peroxides), and (v) the cyclization giving the basicity order: oxetane > tetrahydrofuran > tetrahydropyran > oxirane. A spectroscopic scale of hydrogen‐bond basicity is constructed from the infrared frequency shift Δν(OH) of methanol hydrogen‐bonded to peroxides and ethers. The thermodynamic pKHB scale does not correlate with the ν(OH) scale because of (i) statistical effects in polyethers and peroxides (ii) secondary hydrogen‐bond acceptor sites (e.g. in benzyl ether), (iii) variations of the s character of oxygen lone pairs either by conjugation or cyclization, (iv) steric effects, (v) lone‐pair–lone‐pair repulsions, and (vi) anomeric effects. The ν(OH···O) band shape reveals two stereoisomeric complexes, the most stable being tetrahedral at the ether oxygen atom.

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Section: Methodsmentioning

confidence: 99%

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confidence: 99%

The Hydrogen-Bond Basicity pKHB Scale of Peroxides and Ethers

1998

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“…16–19 The thioamide NH is a stronger hydrogen bond donor than the oxoamide NH, while the sulfur is a slightly weaker hydrogen bond acceptor than the corresponding oxygen. 20–23 The thioamide sulfur is also more reactive as a nucleophile, reactivity commonly observed in cyclization during Edman degradation. 24,25 Despite these differences, the thioamide is generally stable at physiological pH and can be incorporated in an α-helix or a β-turn without grossly perturbing secondary structure.…”

Section: Introductionmentioning

confidence: 99%

Native Chemical Ligation of Thioamide-Containing Peptides: Development and Application to the Synthesis of Labeled α-Synuclein for Misfolding Studies

Batjargal

Wang²,

Goldberg³

et al. 2012

J. Am. Chem. Soc.

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Thioamide modifications of the peptide backbone are used to perturb secondary structure, to inhibit proteolysis, as photoswitches, and as spectroscopic labels. Thus far, their incorporation has been confined to single peptides synthesized on solid phase. We have generated thioamides in C-terminal thioesters or N-terminal Cys fragments and examined their compatibility with native chemical ligation conditions. Most sequence variants can be coupled in good yields with either TCEP or DTT as the reductant, though some byproducts are observed with prolonged TCEP incubations. Furthermore, we find that thioamides are compatible with thiazolidine protection of an N-terminal Cys, so that multiple ligations can be used to construct larger proteins. Since the acid-lability of the thioamide prohibits on-resin thioester synthesis using Boc chemistry, we devised a method for the synthesis of thioamide peptides with a masked C-terminal thioester that is revealed in situ. Finally, we have shown that thioamidous peptides can be coupled to expressed protein fragments to generate large proteins with backbone thioamide labels by synthesizing labeled versions of the amyloid protein α-synuclein for protein folding studies. In a proof-of-principle experiment, we demonstrated that quenching of fluorescence by thioamides can be used to track conformational changes during aggregation of labeled α-synuclein.

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“…In docking, no binding of sulfur to zinc is observed. This could be due to the lower basicity of the thioamide versus the thiourea [24]. In compound 50, the substituent of the thioimidazole mimicks the transetrans configuration of the thiourea.…”

Section: Structureeactivity Relationships For the Zinc-binding Groupmentioning

confidence: 99%