A study of the conformations of valinomycin in solution phase

Abstract

Vibrational absorption and vibrational circular dichroism (VCD) spectra of valinomycin are measured, in different solvents, in the ester and amide carbonyl stretching regions. The influence of cations, namely Li(+), Na(+), K(+), and Cs(+), in methanol-d(4) solvent is also investigated. Ab initio quantum mechanical calculations using density functional theory and 6-31G* basis set are used to predict the absorption and VCD spectra. A bracelet-type structure for valinomycin that reproduces the experimental absorption and VCD spectra in inert solvents is identified. For the structure of valinomycin in polar solvents, a propeller-type structure was optimized, but further investigations are required to confirm this structure. A symmetric octahedral environment for the ester carbonyl groups in the valinomycin-K(+) complex is supported by the experimental VCD spectra. The results obtained in the present study demonstrate that even for large macrocyclic peptides, such as valinomycin, VCD can be used as an independent structural tool for the study of conformations in solution.

NMR evidence of a valinomycin–proton complex

“…[5][6][7][8][9][10][11][12][13][14][15][16] It should thus require a certain ion radius, ideally that of K þ (or larger). This idea has been supported by the known difference of three to four orders of magnitude between the stability constants of the K þ and Na þ complexes of valinomycin [17][18][19] and thus led to the conclusion that the structure of the latter complex must be different.…”

“…This idea has been supported by the known difference of three to four orders of magnitude between the stability constants of the K þ and Na þ complexes of valinomycin [17][18][19] and thus led to the conclusion that the structure of the latter complex must be different. 16 An even more different structure should thus be expected in the case of the proton complex (although, owing to the presence of small amounts of water, the proton is probably present in the form of hydroxonium ion H 3 O þ ). However, the shifts of the 1 H NMR signals and changes of the 3 J NHCH splitting constants observed by us under H þ coordination are quite analogous to those observed [5][6][7][8][9][10] with K þ , thus indicating that the conformation of valinomycin and thus the structure of the complex are virtually the same in both cases.…”

“…[1][2][3][4] The ability of valinomycin to carry ions is primarily due to the formation of a molecular complex. As revealed in particular for the K þ complex by NMR, [5][6][7][8][9][10][11] infrared spectra, 5-9 X-ray diffraction, [12][13][14][15] and other techniques (see reference 16 and references therein), the complex formation requires a change in the conformation of the depsipeptide ring, after which the six peptide units fortify a bracelet-like form of the molecule by intramolecular hydrogen bonds and the six carbonyls of the carboxylic ester groups adopt a hexadentate formation binding the metal cation by a polycentric dipolar bond. The change is more dramatic in polar media, in which valinomycin has a propeller-like conformation 16 due to intermolecular hydrogen bonds with the solvent.…”

“…It is believed 16 that a high stability of the complex requires a certain radius of the central ion thus giving a tight packing of the coordination cavity. In accord with this idea, valinomycin was found to be a selective K þ carrier, the stability of its complex with potassium ion being three to four orders of magnitude higher than that with sodium ion.…”

The early development and application of FTIR difference spectroscopy to membrane proteins: A personal perspective

“…Our Raman studies confirmed the existence of β-type hydrogen bonding when gramicidin A was solubilized in a hydrophobic solvent similar to the hydrophobic interior of lipid bilayers. Many subsequent vibrational studies have been made on both VM and Gramicin A [60,169,244,248].…”