Khan, Ahsan Ali (2017) Experimental and theoretical vibrational spectroscopic studies of diketopiperazines. PhD thesis, University of Greenwich.

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Abstract

The diketopiperazine (DKP) cyclo(L-homoCySH-L-homoCySH) (C-CySH) has been synthesised by a method reported in the literature. DFT calculations of molecular structures and their associated vibrational modes were conducted at the B3LYP/aug-cc-pVTZ level. The two calculated minimum energy structures of C-CySH display boat conformations, with C1 and C2 symmetry. The solid state Raman and IR spectra for C-CySH and its deuterated isotopomer are reported. The strong band at 1662 cm-1 observed in IR and at 1663 cm-1 in the Raman spectrum is assigned to the C=O stretching mode (cis amide I mode). On deuteration the cis amide I band shows a downward shift of around 54 cm-1 in the Raman spectrum; this can be attributed to stronger coupling and high N-H character compared with other DKPs. The cis amide II mode is found at 1506 cm-1 (Raman). This band is found at a significantly higher wavenumber than that of other DKPs where the ring, essentially, adopts a boat conformation.

The degradation of D-cycloserine was examined by 1H-NMR spectroscopy. The resulting degradation products, 3,6-bis(aminoxymethyl)-piperazine-2,5-dione (AMDKP) and 3,6-dimethylene-piperazine-2,5-dione (DMDKP), were synthesised and their Raman and IR spectra obtained in both the solid and aqueous solution state (AMDKP) and in the solid state only (DMDKP). DFT calculations of molecular structures and their associated vibrational modes were conducted at the B3LYP/aug-cc-pVTZ level. The calculated minimum energy structures of AMDKP (C2) and DMDKP (C2h) have boat and planar conformations, respectively. Due to intermolecular hydrogen bonding with neighbouring molecules it is suggested that in AMDKP, the N-H bonds of the DKP appear at lower wavenumbers (between 3165 cm-1 and 3182 cm-1) compared with the aminoxymethyl side-chain NH2 vibrations (between ∼3204 cm−1 and 3342 cm−1) in both solid state IR and Raman spectra. The strong bands located at 1659 cm-1 and 1655 cm-1 in the IR and Raman spectra are assigned to the C=O stretching mode (cis amide I mode) in AMDKP. The cis amide II vibration is detected at 1502 cm-1 in AMDKP. In DMDKP, the cis amide II mode is located at 1499 cm-1 and shifts to lower wavenumbers on N-deuteration (by ∼50 cm-1). It is hypothesised that due to the resonance effect associated with the dimethylene side-chain in DMDKP, the cis amide II mode may have a dramatic effect on its location compared to planar or near-planar DKPs.

Investigations of the Raman and IR spectra, of the DKPs N,N'-diacetyl-cyclo(Gly-Gly) (DAGG) and N,N'-dimethyl-cyclo(Gly-Gly) (DMGG) are reported and compared/contrasted with the parent DKP cyclo(Gly-Gly) in both the solid (powdered) and aqueous states. DFT calculations of the structures of the isolated molecules, in the gas phase, and their associated vibrational modes were conducted using the hybrid SCF-DFT B3LYP method in conjunction with the aug-cc-pVTZ basis set. The calculated minimum energy structures of DAGG and DMGG both display boat conformations with C2 symmetry. The Raman and IR spectra for DAGG show a significant decrease in wavenumber of the ring amide C-N stretching vibration compared to the parent DKP, resulting from a shortening of the ring C=O and lengthening of the C-N bonds. Unlike DAGG, there is no significant difference in C-N bond lengths for DMGG.

IR and Raman spectra of histidine containing DKPs, cyclo(L-His-L-Pro) (CHP), cyclo(D-His-L-Pro) (CDHP) and cyclo(L-Ala-L-His) (CAH), are reported in both the solid and solution state. Conformational analyses were carried out for the two tautomers of each molecule. DFT calculations of molecular structures and their associated vibrational modes were conducted at the B3LYP/aug-cc-pVTZ level. The experimental vibrational spectroscopic results are discussed together with the calculated data obtained for the lowest energy conformers of the two tautomers. The strong bands at 1645 and 1648 cm-1 (infra-red) and at 1649 and 1650 cm-1 in the Raman spectra of CHP and CDHP are assigned to the (C=O) stretch mode (cis amide 1 mode). In the case of CAH, this mode appears at 1671 cm-1 in the IR spectrum and at 1662 cm-1 in the Raman spectrum. The cis amide II mode is found at 1495, 1498 and 1496 cm-1 in the solid-state Raman spectra of CHP, CDHP and CAH, respectively. In the solution state this band is found at 1518, 1512 and 1523 cm-1 in the Raman spectra of CHP, CDHP and CAH, respectively. This mode shows a downward shift of ∼10-20 cm-1 in the Raman spectra of CHP, CDHP and CAH in D2O.

Investigations of the IR and Raman spectra of 2,3-DKP, 2,6-DKP and hexahydropyrimidine-4,5-dione (4,5-HHP) are reported and compared/contrasted with the 2,5-DKP regioisomer in both the solid (powdered) and aqueous states. DFT calculations at the B3LYP/aug-cc-pVTZ level, were employed in order to obtain the minimum energy structures of the three compounds. Due to intermolecular hydrogen bonding with neighbouring molecules it is suggested that in the case of 2,6-DKP, two N-H stretching bands are observed at different wavenumbers owing to the presence of N-H groups in different locations. Compared to the amide I mode of 2,5-DKP (located at ~1655 cm-1) in the solid state Raman spectrum, it is apparent that the vibrational bands for the ring C=O stretch of 2,3-DKP and 2,6-DKP appear at a significantly higher wavenumber (~40-50 cm-1). The decrease in wavenumbers (cm-1) of the C-N stretching vibrations (cis amide II) in 2,3-DKP, 2,6-DKP and 4,5-HHP can be attributed to the strong coupling of C-N vibrations with N-H in-plane-bending and CH2 bending vibrations.

Item Type:	Thesis (PhD)
Uncontrolled Keywords:	Chemistry; diketopiperazines (DKPs); vibrational spectroscopy; computational chemistry;
Subjects:	Q Science > QC Physics Q Science > QD Chemistry
Faculty / School / Research Centre / Research Group:	Faculty of Engineering & Science Faculty of Engineering & Science > School of Science (SCI)
Last Modified:	24 Apr 2019 12:07
URI:	http://gala.gre.ac.uk/id/eprint/23698

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