Temperature-dependent changes in the folding pattern of a simple triamide

Abstract

We describe the conformational behavior of triamide 1' in methylene chloride solution. Triamide 1 has several alternative folding patterns available to it, but at low temperatures in this relatively non-interactive solvent, one highly ordered conformation predominates. The non-covalent forces at work in 1 include amide-amide hydrogen bonding, one of the principal conformation-specifying factors in proteins. The examination of oligoamides under conditions in which conformation is determined by a relatively small number of internal non-covalent interactions is the basis of our effort to understand the interplay of the non-covalent forces that influence protein secondary and tertiary structural stability.2 R R CH, n. 0 1 Insight on the conformational behavior of triamide 1 in CD2C12 is provided by the temperature dependences of the amide proton NMR chemical shifts ( Figure 1). The data for 1 are juxtaposed with the data for diamides 2 and 3,' which model respectively the six-and seven-membered-ring hydrogen bonds available to the triamide. Also shown are the data for a 1:l mixture of Nmethylacetamide and N,N-dimethylacetamide, indicating the inherent chemical shift temperature dependence for a non-hydrogen bonded amide proton (intermolecular hydrogen bonding is minimal under these conditions)). It is immediately clear that the folding patterns experienced by 1 in CD2C12 include conformations other than those involving the six-and seven-membered-ring amide-amide hydrogen bonds.In a very weakly hydrogen bonding solvent, both the absolute value and the temperature dependence of the amide proton chemical shift provide structural i n f~r m a t i o n .~,~ Under these conditions, the rate at which an amide proton exchanges among its various hydrogen bonded and non-hydrogen bonded states is usually rapid on the NMR time scale. Therefore, the lone signal observed for a given amide proton represents a weighted average of the signals for that proton in its alternative environments, with more time in a hydrogen bonded state moving the signal further downfield.5 The substantial difference between the observed amide proton chemical shifts for diamides 2 and 3 at all temperatures indicates that much more intramolecular hydrogen bonding occurs in 2 than in 3. This qualitative conclusion is confirmed by the infrared spectra of these two diamides in dilute CH2C12 solution at room temperature: the N-H stretch region for diamide 2 is dominated by a broad hydrogen bonded N-H (1) All new amides were prepared by standard methods, which will be presented in a full paper. The NMR, IR, and high-resolution mass spectroscopic data for each new compound are consistent with the proposed structure.(2) Gellman, S. H.; Adams, B. R. Tetrahedron Leu. 1989, 30, 3381.(3) The chemical shift temperature dependence data shown in Figure 1 were obtained with 1 mM amide solutions. When a 5 mM solution of 1 was examined, little variation was observed in the behavior of Hb, relative to the I mM sample, over the entire temperature range. Below 253 K, however, t...

The nucleation of monomeric parallel β-sheet-like structures and their self-assembly in aqueous solution

“…9,52,56 The temperature dependence of the chemical shift is less reliable than the FT-IR data, e.g. in cyclic systems and in rare acyclic systems where the enthalpies of the equilibrating conformations are similar, the temperature dependencies of the amide NH chemical shift show opposite trends to those discussed directly above.…”

Structural studies of spiroarsoranes derived from 2-aminophenols

“…It has been accepted that the 1 H NMR chemical shifts dependence on the temperature ( δ/ T) is a diagnostic tool to elucidate, if the hydrogen atom has intra-intermolecular or solvent interactions. Accordingly, when the values ( δ/ T) are higher than 4 × 10 −3 ppm/K, solvated X-H groups are present; on the other hand, values lower than 3 × 10 −3 ppm/K are attributed to X-H groups with intramolecular hydrogen bonding [8][9][10]. We studied the nature of hydrogen bonding by variable temperature 1 H NMR ( δ/ T) in compounds 5-7.…”

Estudio estructural de interacciones intra- e intermoleculares basadas en puentes de hidrógeno en piridin-2,6-dicarboxamidas

“…Los espectros de infrarrojo de las amidas 15 mostraron dos bandas para las vibraciones de tensión () del grupo NH; la primera en el intervalo de 3407 a 3323 cm −1 y la segunda entre 3297 y 3231 cm −1 . Las vibraciones de tensión del grupo NH a frecuencias menores (3297 y 3231 cm −1 ) y su comparación con las del grupo NH en amidas que presentan interacciones por enlace por puente de hidrógeno (Gellman et al, 1990), sugieren la presencia de este tipo de interacciones en los compuestos 15. Estas interacciones pueden ser intermoleculares y/o intramoleculares del tipo O···HN y N···HN respectivamente, como las descritas en las estructuras cristalinas para 1 y 2 (Marlin et al, 2000), en donde el rotámero Z,Z es el contribuyente principal en estado sólido para 2, figura 5.…”

“…Puentes de hidrógeno intra-e intermoleculares reportados en las estructuras cristalinas de 1 y 2 (Marlin, et al, 2000) La primera NH en 3407 cm −1 para la amida 1, se asignó a un NH libre por comparación con valores previamente reportados en el intervalo de 3521 a 3400 cm -1 (Gellman et al, 1990), mientras que la segunda observada hacia frecuencias menores en 3231 cm −1 se atribuyó a un puente de hidrógeno intramolecular N···HN (figura 6), los cuales han sido reportados en estado sólido en el intervalo de 3295 a 3230 cm -1 (Alvarez-Hernández et al, 2017); lo anterior es acorde a la interacción intramolecular N···HN descrita por difracción de rayos X de monocristal para esta amida (Marlin et al, 2000). Para las amidas 25, la primera banda de vibración de tensión del grupo NH en el intervalo de 3362 a 3323 cm −1 , se atribuyó a asociaciones intermoleculares CO···HN por comparación con amidas análogas ( = 3373 a 3292 cm −1 ) reportadas por Marlin et al La segunda NH se observó en el intervalo de 3297 a 3243 cm −1 y por comparación con las descritas por Alvarez et al, se atribuyeron a puentes de hidrógeno intramoleculares del tipo N···HN como se muestra en la figura 7.…”