Benchtop NMR analysis of piperazine-based drugs hyperpolarised by SABRE

Piperazine-based drugs, such as N-benzylpiperazine (BZP), became attractive in the 2000s due to possessing effects similar to amphetamines. Herein, BZP, in addition to its pyridyl analogues, 2-, 3-, and 4-pyridylmethylpiperidine (2-PMP, 3-PMP, and 4-PMP respectively) was subjected to the hyperpolarisation technique Signal Amplification By Reversible Exchange (SABRE) in order to demonstrate the use of this technique to detect these piperazine-based drugs. Although BZP was not hyperpolarised via SABRE, 2-PMP, 3-PMP, and 4-PMP were, with the ortho- and meta-pyridyl protons of 4-PMP showing the largest enhancement of 313-fold and 267-fold, respectively, in a 1.4-T detection field, following polarisation transfer at Earth's magnetic field. In addition to the freebase, 4-PMP.3HCl was also appraised by SABRE and was found not to polarise, however, the addition of increasing equivalents of triethylamine (TEA) produced the freebase, with a maximum enhancement observed upon the addition of 3 equivalents of TEA. Further addition of TEA led to a reduction in the observed enhancement. SABRE was also employed to polarise 4-PMP.3HCl (~20% w/w) in a simulated tablet to demonstrate the forensic application of the technique (138-fold enhancement for the ortho-pyridyl protons). The amount of 4-PMP.3HCl present in the simulated tablet was quantified via NMR using D₂O as a solvent and compared well to complimentary gas chromatography–mass spectrometry data. Exchanging D₂O for CD₃OD as the solvent utilised for analysis resulted in a significantly lower amount of 4-PMP.3HCl being determined, thus highlighting safeguarding issues linked to drug abuse in relation to determining the amount of active pharmaceutical ingredient present.     

On sums of powers of inverse complete quotients

For an irrational number , let denote its -th continued fraction inverse complete quotient, obtained by deleting the first partial quotients. For any positive real number , we establish the optimal linear bound on the sum of the -th powers of the first complete quotients. That is, we find the smallest constants such that for all and all irrationals .

     

Rational approximation of vertical segments

In many applications, observations are prone to imprecise measurements. When constructing a model based on such data, an approximation rather than an interpolation approach is needed. Very often a least squares approximation is used. Here we follow a different approach. A natural way for dealing with uncertainty in the data is by means of an uncertainty interval. We assume that the uncertainty in the independent variables is negligible and that for each observation an uncertainty interval can be given which contains the (unknown) exact value. To approximate such data we look for functions which intersect all uncertainty intervals. In the past this problem has been studied for polynomials, or more generally for functions which are linear in the unknown coefficients. Here we study the problem for a particular class of functions which are nonlinear in the unknown coefficients, namely rational functions. We show how to reduce the problem to a quadratic programming problem with a strictly convex objective function, yielding a unique rational function which intersects all uncertainty intervals and satisfies some additional properties. Compared to rational least squares approximation which reduces to a nonlinear optimization problem where the objective function may have many local minima, this makes the new approach attractive.     

On groups with conjugacy classes of distinct sizes

A finite group G is called an ah-group if any two distinct conjugacy classes of G have distinct cardinality. We show that if G is an ah-group, then the non-abelian socle of G is isomorphic to one of the following:

1. , for 1a5, a≠2.

2. A₈.

3. PSL(3,4)^e, for 1e10.

4. A₅×PSL(3,4)^e, for 1e10.

Based on this result, we virtually show that if G is an ah-group with π(G) 2,3,5,7 , then F(G)≠1, or equivalently, that G has an abelian normal subgroup.In addition, we show that if G is an ah-group of minimal size which is not isomorphic to S₃, then the non-abelian socle of G is either trivial or isomorphic to one of the following:

1. , for 3a5.

2. PSL(3,4)^e, for 1e10.

Our research lead us to interesting results related to transitivity and homogeneousity in permutation groups, and to subgroups of wreath products of form Z₂S_n. These results are of independent interest and are located in appendices for greater autonomy.     

Anomalous dispersion in the Belousov-Zhabotinsky reaction: Experiments and modeling

We report results on dispersion relations and instabilities of traveling waves in excitable systems. Experiments employ solutions of the 1,4-cyclohexanedione Belousov-Zhabotinsky reaction confined to thin capillary tubes which create a pseudo-one-dimensional system. Theoretical analyses focus on a three-variable reaction-diffusion model that is known to reproduce qualitatively many of the experimentally observed dynamics. Using continuation methods, we show that the transition from normal, monotonic to anomalous, single-overshoot dispersion curves is due to an orbit flip bifurcation of the solitary pulse homoclinics. In the case of “wave stacking”, this anomaly induces attractive pulse interaction, slow solitary pulses, and faster wave trains. For “wave merging”, wave trains break up in the wake of the slow solitary pulse due to an instability of wave trains at small wavelength. A third case, “wave tracking” is characterized by the non-existence of solitary waves but existence of periodic wave trains. The corresponding dispersion curve is a closed curve covering a finite band of wavelengths.     

Cortical disinhibition occurs in chronic neuropathic,but not in chronic nociceptive pain

Background  

The aim of this study was to examine the relationship between chronic neuropathic pain after incomplete peripheral nerve lesion, chronic nociceptive pain due to osteoarthritis, and the excitability of the motor cortex assessed by transcranial magnetic stimulation (TMS). Hence in 26 patients with neuropathic pain resulting from an isolated incomplete lesion of the median or ulnar nerve (neuralgia), 20 patients with painful osteoarthritis of the hand, and 14 healthy control subjects, the excitability of the motor cortex was tested using paired-pulse TMS to assess intracortical inhibition and facilitation. These excitability parameters were compared between groups, and the relationship between excitability parameters and clinical parameters was examined.     

Analytic Continuation of Dirichlet Series with Almost Periodic Coefficients

We consider Dirichlet series z_g,a(s)=?_n=1^￥ g(na) e^{-l_n s}{\zeta_{g,\alpha}(s)=\sum_{n=1}^\infty g(n\alpha) e^{-\lambda_n s}} for fixed irrational α and periodic functions g. We demonstrate that for Diophantine α and smooth g, the line Re(s) = 0 is a natural boundary in the Taylor series case λ _n  = n, so that the unit circle is the maximal domain of holomorphy for the almost periodic Taylor series ?_n=1^￥ g(na) zⁿ{\sum_{n=1}^{\infty} g(n\alpha) z^n}. We prove that a Dirichlet series z_g,a(s) = ?_n=1^￥ g(n a)/n^s{\zeta_{g,\alpha}(s) = \sum_{n=1}^{\infty} g(n \alpha)/n^s} has an abscissa of convergence σ ₀ = 0 if g is odd and real analytic and α is Diophantine. We show that if g is odd and has bounded variation and α is of bounded Diophantine type r, the abscissa of convergence σ ₀ satisfies σ ₀ ≤ 1 − 1/r. Using a polylogarithm expansion, we prove that if g is odd and real analytic and α is Diophantine, then the Dirichlet series ζ _g,α (s) has an analytic continuation to the entire complex plane.