Vibrational spectroscopic studies of the structure of di-amino acid peptides. Part II: cyclo(L-Asp-L-Asp) in the solid state and in aqueous solution

Solid-state protonated and N,O-deuterated Fourier transform infrared (IR) and Raman scattering spectra together with the protonated and deuterated Raman spectra in aqueous solution of the cyclic di-amino acid peptide cyclo(L-Asp-L-Asp) are reported. Vibrational band assignments have been made on the basis of comparisons with previously cited literature values for diketopiperazine (DKP) derivatives and normal coordinate analyses for both the protonated and deuterated species based upon DFT calculations at the B3-LYP/cc-pVDZ level of the isolated molecule in the gas phase. The calculated minimum energy structure for cyclo(L-Asp-L-Asp), assuming C-2 symmetry, predicts a boat conformation for the DKP ring with both the two L-aspartyl side chains being folded slightly above the ring. The C=O stretching vibrations have been assigned for the side-chain carboxylic acid group (e.g. at 1693 and 1670 cm(-1) in the Raman spectrum) and the cis amide I bands (e.g. at 1660 cm(-1) in the Raman spectrum). The presence of two bands for the carboxylic acid C=O stretching modes in the solid-state Raman spectrum can be accounted for by factor group splitting of the two nonequivalent molecules in a crystallographic unit cell. The cis amide II band is observed at 1489 cm(-1) in the solid-state Raman spectrum, which is in agreement with results for cyclic di-amino acid peptide molecules examined previously in the solid state, where the DKP ring adopts a boat conformation. Additionally, it also appears that as the molecular mass of the substituent on the C-alpha atom is increased, the amide II band wavenumber decreases to below 1500 cm(-1); this may be a consequence of increased strain on the DKP ring. The cis amide II Raman band is characterized by its relatively small deuterium shift (29 cm(-1)), which indicates that this band has a smaller N-H bending contribution than the trans amide II vibrational band observed for linear peptides.

IR/Raman spectroscopy and DFT calculations of cyclic di-amino acid peptides. Part III: comparison of solid state and solution structures of cyclo(L-Ser-L-Ser)

B3-LYP/cc-pVDZ calculations of the gas-phase structure and vibrational spectra of the isolated molecule cyclo(L-Ser-L-Ser), a cyclic di-amino acid peptide (CDAP), were carried out by assuming C-2 symmetry. It is predicted that the minimum-energy structure is a boat conformation for the diketopiperazine (DKP) ring with both L-Beryl side chains being folded slightly above the ring. An additional structure of higher energy (15.16 kJ mol(-1)) has been calculated for a DKP ring with a planar geometry, although in this case two fundamental vibrations have been calculated with imaginary wavenumbers. The reported X-ray crystallographic structure of cyclo(L-Ser-L-Ser), shows that the DKP ring displays a near-planar conformation, with both the two L-Beryl side chains being folded above the ring. It is hypothesized that the crystal packing forces constrain the DKP ring in a planar conformation and it is probable that the lower energy boat conformation may prevail in the aqueous environment. Raman scattering and Fourier-transform infrared (FT-IR) spectra of solid state and aqueous solution samples of cyclo(L-Ser-L-Ser) are reported and discussed. Vibrational band assignments have been made on the basis of comparisons with the calculated vibrational spectra and band wavenumber shifts upon deuteration of labile protons. The experimental Raman and IR results for solid-state samples show characteristic amide I vibrations which are split (Raman:1661 and 1687 cm(-1), IR:1666 and 1680 cm(-1)), possibly due to interactions between molecules in a crystallographic unit cell. The cis amide I band is differentiated by its deuterium shift of ~ 30 cm(-1), which is larger than that previously reported for trans amide I deuterium shifts. A cis amide II mode has been assigned to a Raman band located at 1520 cm(-1). The occurrence of this cis amide II mode at a wavenumber above 1500 cm(-1) concurs with results of previously examined CDAP molecules with low molecular weight substituents on the C-alpha atoms, and is also indicative of a relatively unstrained DKP ring.

Vibrational spectroscopy and crystal structure analysis of two polymorphs of the di-amino acid peptide cyclo(L-Glu-L-Glu)

Cyclo(L-Glu-L-Glu) has been crystallised in two different polymorphic forms. Both polymorphs are monoclinic, but form 1 is in space group P21 and form 2 is in space group C2. Raman scattering and FT-IR spectroscopic studies have been conducted for the N,O-protonated and deuterated derivatives. Raman spectra of orientated single crystals, solid-state and aqueous solution samples have also been recorded. The different hydrogen-bonding patterns for the two polymorphs have the greatest effect on vibrational modes with N&bond;H and C&dbond;O stretching character. DFT (B3-LYP/cc-pVDZ) calculations of the isolated cyclo(L-Glu-L-Glu) molecule predict that the minimum energy structure, assuming C2 symmetry, has a boat conformation for the diketopiperazine ring with the two L-Glu side chains being folded above the ring. The calculated geometry is in good agreement with the X-ray crystallographic structures for both polymorphs. Normal coordinate analysis has facilitated the band assignments for the experimental vibrational spectra. Copyright © 2009 John Wiley & Sons, Ltd.

Stochastic monotonicity and duality for continuous time Markov chains with general q-Matrix

The key problems in discussing stochastic monotonicity and duality for continuous time Markov chains are to give the criteria for existence and uniqueness and to construct the associated monotone processes in terms of their infinitesimal q -matrices. In their recent paper, Chen and Zhang [6] discussed these problems under the condition that the given q-matrix Q is conservative. The aim of this paper is to generalize their results to a more general case, i.e., the given q-matrix Q is not necessarily conservative. New problems arise 'in removing the conservative assumption. The existence and uniqueness criteria for this general case are given in this paper. Another important problem, the construction of all stochastically monotone Q-processes, is also considered.

Uniqueness criteria for continuous-time Markov chains with general transition structures

We derive necessary and sufficient conditions for the existence of bounded or summable solutions to systems of linear equations associated with Markov chains. This substantially extends a famous result of G. E. H. Reuter, which provides a convenient means of checking various uniqueness criteria for birth-death processes. Our result allows chains with much more general transition structures to be accommodated. One application is to give a new proof of an important result of M. F. Chen concerning upwardly skip-free processes. We then use our generalization of Reuter's lemma to prove new results for downwardly skip-free chains, such as the Markov branching process and several of its many generalizations. This permits us to establish uniqueness criteria for several models, including the general birth, death, and catastrophe process, extended branching processes, and asymptotic birth-death processes, the latter being neither upwardly skip-free nor downwardly skip-free.

Financing of SME's: an asset side story

The main sources of financing for small and medium sized enterprises (SMEs) are equity (internally generated cash), trade credit paid on time, long and short term bank credits, delayed payment on trade credit and other debt. The marginal costs of each financing instrument are driven by asymmetric information (cost of gathering and analysing information) and transactions costs associated with non-payment (costs of collecting and selling collateral). According to the Pecking Order Theory, firms will choose the cheapest source in terms of cost. In the case of the static trade-off theory, firms choose finance so that the marginal costs across financing sources are all equal, thus an additional Euro of financing is obtained from all the sources whereas under the Pecking Order Theory the source is determined by how far down the Pecking Order the firm is presently located. In this paper, we argue that both of these theories miss the point that the marginal costs are dependent of the use of the funds, and the asset side of the balance sheet primarily determines the financing source for an additional Euro. An empirical analysis on a unique dataset of Portuguese SME's confirms that the composition of the asset side of the balance sheet has an impact of the type of financing used and the Pecking Order Theory and the traditional Static Trade-off theory are rejected.

Managing the supply side for product development in China: a Guanxi network approach

Based on the IMP research tradition this paper regards relationships and networks as key issues in the product development and supply management agenda. Within business networks, co-development is only possible to be analysed when emphasis is placed on interdependences and interactive relationships. Co-development usually implies close relationships that allow companies to rely on each other's resources. Close relationships imply interdependences, which may improve companies' technical and product development. By looking at the actual interactions - between a UK company and its Chinese suppliers - that led to an innovative solution and a successful product launch, evolving relationship patterns are identified and analysed in a case study. Both the literature review and case study findings highlight the importance of the 'guanxi' concept (meaning interpersonal relationships in Mandarin) when analysing business-to-business networks in China. Hence, it is suggested that guanxi-based thinking and acting should be incorporated into the interaction model when considering business networking that embrace China. 'Guanxi' broadens the validity of the interaction model, in terms of geographical proximity, and deepens its theoretical base. The case study provides valuable insights for supply management under a product development context in China. In practice, the main point of interest is that Chinese suppliers are important 'resource' providers as well as 'network' providers. Hence, it is suggested that guanxi practice should be reflected into theoretical developments.