Solid state NMR, IR and X-ray diffraction studies of the structure and motion of L-leucinamide

Abstract

Crystalline L-leucinamide has been studied by 13 C CP/MAS NMR, FTIR spectroscopy and X-ray crystallography. The 13 C CP/MAS spectrum of crystalline L-leucinamide has been assigned using the depolarisation-repolarisation method. Two magnetically non-equivalent molecules in the unit cell have been found from the 13 C CP/MAS spectra. Non-equivalence is also observed in the FTIR spectrum. The molecular dynamics were studied by measuring 13 C spin-lattice relaxation in both laboratory and rotating frames. Results show that the mobilities of the two molecules are very different. Spin-lattice relaxation times for the two carbons differ by an order of magnitude. Determination of the crystal structure by Xray crystallography confirmed the existence of two distinct molecules in the unit cell; these differed in the orientation of the amide groups and in their involvement in the hydrogen bonding scheme, which may account for the observed NMR behaviour.

Rotational Spectra and Computational Analysis of Two Conformers of Leucinamide

“…The backbone structures of crystal-phase leucinamide are different from the gas-phase structures with Ψ = +103.06(49) and −50.04(63)° for conformers I and II, respectively, as compared to Ψ = −36.5 and −14.5° for conformers 1 and 2, respectively, of this work. These differences can be attributed to the differences between the intermolecular hydrogen bonding dominant in the crystal structures and the intramolecular hydrogen bonding controlling the gas-phase structures.…”

“…These differences can be attributed to the differences between the intermolecular hydrogen bonding dominant in the crystal structures and the intramolecular hydrogen bonding controlling the gas-phase structures. The X-ray crystal structures of leucinamide exhibit similar side chain configurations for both conformers with χ 1 = 58.72(79) and 61.47(75)° for conformers I and II, respectively, and χ 2 = −175.10(121) and −174.20(84)° for conformers I and II, respectively . The side chain configurations for the gas-phase structures in this work are markedly different with χ 1 = 53.7 and 175.7° for conformers 1 and 2, respectively, and χ 2 = −59.8 and 65.4° for conformers 1 and 2, respectively.…”

“…Two conformers of leucinamide were identified by X-ray crystallography and crystal-phase NMR and FTIR spectroscopies. 14,15 The two solid-phase structures have different backbone configurations resulting from different intermolecular hydrogen bonding interactions; the side chain configurations in the crystal structures are similar. 14,15 Because intermolecular hydrogen bonding is crucial to the conformational preferences in the crystal phase, we expect differences in the monomer gas-phase structures where these forces are absent.…”

“…14,15 The two solid-phase structures have different backbone configurations resulting from different intermolecular hydrogen bonding interactions; the side chain configurations in the crystal structures are similar. 14,15 Because intermolecular hydrogen bonding is crucial to the conformational preferences in the crystal phase, we expect differences in the monomer gas-phase structures where these forces are absent. Two conformers of the amino acid leucine were identified in the gas phase recently using Fourier transform microwave (FTMW) spectroscopy.…”

Solid-State Nuclear Magnetic Resonance Spectroscopy-Pharmaceutical Applications

“…As discussed earlier, a number of useful solid‐state NMR methods are now available to perform resonance assignments. The CPPI experiment and its variants have been used to analyze a wide range of compounds, including amorphous humic materials,204 crystalline calcipotriol monohydrate and vitamin D,205 crystalline and amorphous forms of delavirdine mesylate,206 and crystalline L ‐leucinamide 207. A series of editing spectra, obtained for lisinopril dihydrate, are compared with the conventional 13 C CP/MAS and TOSS spectra in Figure 1 136.…”