Model dipeptides incorporating the trans cyclohexane analogues of phenylalanine: further evidence of the relationship between side-chain orientation and β-turn type

In order to study the influence of the side-chain orientation on the peptide backbone conformation we have synthesised the model dipeptides t-BuCO-l-Pro-(1S,2R)-c₆Phe-NHMe and t-BuCO-l-Pro-(1R,2S)-c₆Phe-NHMe, incorporating each enantiomer of the trans cyclohexane analogue of phenylalanine (trans-1-amino-2-phenylcyclohexanecarboxylic acid). The orientation of the aromatic side-chain determines the β-turn type accommodated by these peptides to the point that the (1S,2R)-c₆Phe derivative retains the type I β-turn in the crystalline state, in contrast to the behaviour exhibited by the natural counterpart t-BuCO-l-Pro-l-Phe-NHMe.     

Optimisation of the connection between TA-MS systems together with improved data interpretation for TA-MS applications

TA-MS provides chemical and thermal response information. In order for this information to be meaningful sampling must be performed with minimum dead volume and without cold spots. Dead volume leads to response lag and peak broadening. Cold spots result in sample condensation, leading to inaccurate data and potentially inlet blockage. This paper describes a hot zone inlet system and 'in-situ' probe both of which provide fast response, zero dead volume sampling directly to the MS. The paper also discusses data interpretation methodologies and introduces 'soft ionisation' as a means of providing simplified analysis of complex mixtures. This revised version was published online in July 2006 with corrections to the Cover Date.     

Extrapolated Smoothing Descent Algorithm for Constrained Nonconvex and Nonsmooth Composite Problems*

In this paper, the authors propose a novel smoothing descent type algorithm with extrapolation for solving a class of constrained nonsmooth and nonconvex problems,where the nonconvex term is possibly nonsmooth. Their algorithm adopts the proximal gradient algorithm with extrapolation and a safe-guarding policy to minimize the smoothed objective function for better practical and theoretical performance. Moreover, the algorithm uses a easily checking rule to update the smoothing parameter to ensure that any accumulation point of the generated sequence is an (affine-scaled) Clarke stationary point of the original nonsmooth and nonconvex problem. Their experimental results indicate the effectiveness of the proposed algorithm.     

Data loci in algebraic optimization

We consider parametric optimization problems from an algebraic viewpoint. The idea is to find all of the critical points of an objective function thereby determining a global optimum. For generic parameters (data) in the objective function the number of critical points remains constant. This number is known as the algebraic degree of an optimization problem. In this article, we go further by considering the inverse problem of finding parameters of the objective function so it gives rise to critical points exhibiting a special structure. For example if the critical point is in the singular locus, has some symmetry, or satisfies some other algebraic property. Our main result is a theorem describing such parameters.     

Separation of chlamydosporol epimers by reversed-phase HPLC using commercial solvent optimisation software

Summary Two epimers of the mycotoxin chlamydosporol were separated by HPLC on an RP-18 column using a quaternary mobile phase consisting of water (79.1%), methanol (10.0%), acetonitrile (10.4%) and tetrahydrofuran (0.5%), with a flow rate of 1 ml min^–1. This optimal composition of mobile phase, with which the resolution value for the two epimers (1 and2) was 2.73 with retention times of 5.88 and 7.12 min, respectively, was achieved by the application of Philips Solvent Optimisation Software PU 6100. The presence of free silanols on the stationary phase was shown to be an essential requirement for the separation of the chlamydosporol epimers.     

Location of saddle points and minimum energy paths by a constrained simplex optimization procedure

Two methods are proposed, one for the location of saddle points and one for the calculation of steepest-descent paths on multidimensional surfaces. Both methods are based on a constrained simplex optimization technique that avoids the evaluation of gradients or second derivative matrices. Three chemical reactions of increasing structural complexity are studied within the PRDDO SCF approximation. Predicted properties of reaction hypersurfaces are in good overall agreement with those determined by gradient minimization and gradient following algorithms in connection with various ab initio SCF methods. Computational efforts required by the new procedures are discussed.     

An efficient and stereodivergent synthesis of threo- and erythro-β-methylphenylalanine. Resolution of each racemic pair by semipreparative HPLC

threo and erythro diastereoisomers of the constrained amino acid (βMe)Phe can be obtained separately on a multigram scale through a three-step synthesis from the corresponding Z and E isomers of 2-phenyl-4(α-phenylethylidene)-5(4H)-oxazolone. The 5(4H)-oxazolones are readily available from acetophenone and hippuric acid. The four enantiomerically pure isomers of β-methylphenylalanine, (2R,3R)-(βMe)Phe, (2S,3S)-(βMe)Phe, (2R,3S)-(βMe)Phe and (2S,3R)-(βMe)Phe, have been prepared by HPLC resolution of the racemic precursors methyl threo (or erythro)-2-benzamide-3-phenylbutanoates.     

Multivariate optimisation of the experimental conditions for determination of three methylxanthines by reversed-phase high-performance liquid chromatography

Caffeine (1,3,7-trimethylxanthine), theobromine (3,7-dimethylxanthine) and theophylline (1,3-dimethylxanthine) are the most important naturally occurring methylxanthines. Caffeine is a constituent of coffee and other beverage and included in many medicines. Theobromine and theophylline are formed as metabolites of caffeine in humans, and are also present in tea, cocoa and chocolate products.

In order to improve the chromatographic resolution (R_s) with a good analysis time, experimental designs were applied for multivariate optimisation of the experimental conditions of an isocratic reversed-phase high-performance liquid chromatographic (RP-HPLC) method used for the simultaneous determination of caffeine, theobromine and theophylline. The optimisation process was carried out in two steps using full three-level factorial designs. The factors optimised were: flow rate and mobile phase composition. Optimal conditions for the separation of the three methylxanthines were obtained using a mixture of water/ethanol/acetic acid (75:24:1%, v/v/v) as mobile phase and a flow rate of 1.0 mL min⁻¹. The RP-HPLC/UV method was validated in terms of limit of detection (LOD), limit of quantitation (LOQ), linearity, recovery and the precision, calculated as relative standard deviation (R.S.D.). In these conditions, the LOD was 0.10 μg L⁻¹ for caffeine, 0.07 μg L⁻¹ for theobromine and 0.06 μg L⁻¹ for theophylline. The proposed method is fast, requires no extraction step or derivatization and was suitable for quantification of these methylxanthines in coffee, tea and human urine samples.     

N-Alkylation of diethyl acetamidomalonate: synthesis of constrained amino acid derivatives by ring-closing metathesis

An efficient method for N-alkylation of diethyl acetamidomalonate (DEAM) is reported. C-Alkenylation was achieved by treating the N-alkenylated DEAM with various electrophiles in the presence of Cs₂CO₃. RCM reactions of C- and N-alkenylated products gave cyclic amino acid derivatives in good yields.     

Evaluation of the surface tension measurement of axisymmetric drop shape analysis (ADSA) using a shape parameter

A quantitative criterion called “shape parameter” to evaluate the quality of surface tension measurement of Axisymmetric Drop Shape Analysis (ADSA) is presented. ADSA is a powerful technique for the measurement of interfacial tensions and contact angles of pendant drops, sessile drops, and bubbles. Despite the general success of ADSA, deficient results may be obtained for drops close to spherical shape. Therefore, the “shape parameter” was used to determine the range of drop shapes in which ADSA succeeds or fails. The “shape parameter” is a dimensionless parameter that expresses quantitatively the difference in shape between a given experimental profile and an inscribed circle. The surface tension measurements of ADSA were evaluated for both pendant drop and constrained sessile drop configurations using the shape parameter. Different shapes of the pendant drop were studied using different sizes and materials of holders. For each drop configuration, a “critical shape parameter” was defined based on the minimum value of the shape parameter that guarantees an error of less than ±0.1 mJ/m². Furthermore, the effects of the type of liquid and constellation on the “critical shape parameter” were studied.