New designer drug 1-(3-trifluoromethylphenyl) piperazine (TFMPP): gas chromatography/mass spectrometry and liquid chromatography/mass spectrometry studies on its phase I and II metabolism and on its toxicological detection in rat urine

Studies are described on the phase I and II metabolism and the toxicological analysis of the piperazine-derived designer drug 1-(3-trifluoromethylphenyl)piperazine (TFMPP) in rat urine using gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS). The identified metabolites indicated that TFMPP was extensively metabolized, mainly by hydroxylation of the aromatic ring and by degradation of the piperazine moiety to N-(3-trifluoromethylphenyl)ethylenediamine, N-(hydroxy-3-trifluoromethylphenyl)ethylenediamine, 3-trifluoromethylaniline, and hydroxy-3-trifluoromethylaniline. Phase II reactions included glucuronidation, sulfatation and acetylation of phase I metabolites. The authors' systematic toxicological analysis (STA) procedure using full-scan GC/MS after acid hydrolysis, liquid-liquid extraction and microwave-assisted acetylation allowed the detection of TFMPP and its above-mentioned metabolites in rat urine after single administration of a dose calculated from the doses commonly taken by drug users. Assuming similar metabolism, the described STA procedure should be suitable for proof of an intake of TFMPP in human urine.     

5-(N-Arylnortropan-3-yl)- and 5-(N-Arylpiperidin-4-yl)-2,4-diaminopyrimidines. Novel Inhibitors of Dihydrofolate Reductase

Based on a computer-assisted analysis of the three-dimensional structure of the binary complex of E.coli dihydrofolate reductase (DHFR) with methotrexate, 5-(N-arylnortropan-3-yl)- and 5-(N-arylpiperidin-4-yl)-2,4-diaminopyrimidines 2 and 4 were designed as inhibitors of DHFR. Syntheses of the designed compounds have been carried out. The most potent compound 2a inhibited E. coli DHFR with K_i = 0.49.10^?9M. The activities within the series of compounds synthesized could be rationalized by molecular-modelling experiments which served as the basis of this work. Several compounds within the presented series exhibit antimalarial activities in vitro and in vivo.     

Fundamental Aspects of Ionic Dissociations: The Fragmentation Pathways of Excited Bicyclobutane Cations

A most recently developed method to quantify the fragmentation pathways of excited radical cations is presented. Using bicyclobutane cation as an illustrative example, the RRKM analysis of the breakdown diagram determined by He-Iα photoelectron-photoion coincidence spectroscopy is outlined. The results imply complete isomerization to 1,3-butadiene cation preceding the dissociative processes. The rate-energy functions of four competitive primary fragmentation reactions, leading to C₃H, C₄H, C₄H and C₂H are established. There is compelling evidence that the production of C₂H fragment ions does not compete effectively with these four reactions. The extent of kinetic and competitive shift effects is determined. The derived enthalpies of formation are in excellent accord with the available high quality reference data. The relative importance of different fragmentation pathways which ultimately lead to fragment ions of identical mass to charge ratio is assessed.     

Die Strommer-Zykliden des Flaggenraumes

According to H. BRAUNER a flag space is a three-dimensional affine space with an absolute {,f,F}, wheref is a line in the plane of infinity andF a point onf. A cyclide is a surface of order 4 that intersects only atf. A STROMMER-cyclide is a cyclide generated by translation of a circle in an isotropic plane. In this paper we proof that all STROMMER-cyclides can be generated by translation of an isotropic circle along a divergent Newton-parabola or a conic in a full isotropic plane. We give normal-forms and CAD-pictures of these surfaces. Finaly some geometrical results about STROMMER-cyclides are developed.

---

---

Herrn o.Prof. Dr. Gy. Strommer zum 70. Geburtstag gewidmet.     

Concrete quantum logics with covering properties

LetL be a concrete (=set-representable) quantum logic. Letn be a natural number (or, more generally, a cardinal). We say thatL admits intrinsic coverings of the ordern, and writeL C _n , if for any pairA, BL we can find a collection {C _i iI}, where cardI<n andC _i L for anyiI, such thatA B= _il C _i . Thus, in a certain sense, ifLC _n , then the rate of noncompatibility of an arbitrary pairA,BL is less than a given numbern. In this paper we first consider general and combinatorial properties of logics ofC _n and exhibit typical examples. In particular, for a givenn we construct examples ofL C _n+1\C _n . Further, we discuss the relation of the classesC _n to other classes of logics important within the quantum theories (e.g., we discover the interesting relation to the class of logics which have an abundance of Jauch-Piron states). We then consider conditions on which a class of concrete logics reduce to Boolean algebras. We conclude with some open questions.     

Discrepancies in the distribution of prime numbers

Chebyshev has noticed a certain predominance of primes of the form 4n + 3 over those of the form 4n + 1. He asserted that $\text{lim}{}_{\mathrm{x\to \infty }}\text{∑}\text{p > 2}\text{(?1)}{}^{\mathrm{<mtext>(p\; ?\; 1)</mtext><mtext>2</mtext>}}\text{e}{}^{\mathrm{<mtext>?p</mtext><mtext>x</mtext>}}\text{= ?∞}$. This was unproven until today. G. H. Hardy, J. E. Littlewood and E. Landau have shown its equivalence with an analogue to the famous Riemann hypothesis, namely, L(s, χ₁mod 4) ≠ 0, $\text{Re}\text{(s) >}\text{1}\text{2}$. S. Knapowski and P. Turán have given some similar (unproven) relations, e.g., , which are also equivalent to the above. Using Explixit Formulas the author shows that

$\text{lim}{}_{\mathrm{x\to \infty }}\text{∑}\text{p > 2}\text{(?1)}{}^{\mathrm{<mtext>(p\; ?\; 1)</mtext><mtext>2</mtext>}}\text{log}\text{pp}{}^{\mathrm{<mtext>?1</mtext><mtext>2</mtext>}}\text{e}{}^{\mathrm{<mtext>?</mtext><mtext>(</mtext><mtext>log</mtext><mtext>2p)</mtext><mtext>x</mtext>}}\text{= ?∞ (1)}$

holds without any conjecture. (In addition, the order of magnitude of divergence is calculated.) It turns out that (1) is only a special case (in several respects). At first, it may be enlarged into

$\text{lim}{}_{\mathrm{x\to \infty }}\text{∑}\text{p > 2}\text{(?1)}{}^{\mathrm{<mtext>(p\; ?\; 1)</mtext><mtext>2</mtext>}}\text{log}\text{pp}{}^{\mathrm{?\alpha }}\text{e}{}^{\mathrm{<mtext>?</mtext><mtext>(</mtext><mtext>log</mtext><mtext>2p)</mtext><mtext>x</mtext><mtext>)</mtext>}}\text{= ?∞, 0?α?}\text{1}\text{2}\text{.}$

Then, it can be generalised to a wider class of progressions. For example, the same is true if one sums over the primes in the classes 3n + 2 and 3n + 1, with a “?” and a “+” sign, respectively. All results of this type depend on the location of the first nontrivial zero of the corresponding L-series. D. Shanks has given some arguments for the predominance of primes in residue classes of nonquadratic type. He conjectured “If m₁ mod k is a quadratic residue and m₂ mod k a non-residue, then there are “more” primes congruent m₂ than congruent m₁ mod k.” This indeed turns out to be true in the sense of (1), not only for k = 3, 4, but for some higher moduli as well. Finally, numerical calculations were made to investigate the behaviour of Δ₃(X) ? π(X, 2 mod 3) ? π(X, 1 mod 3) in the interval 2 ≤ X ≤ 18, 633, 261. No zero was found in this range. In the analogue case of Δ₄(X) ? π(X, 3 mod 4) ? π(X, 1 mod 4) the first sign change occurs at X = 26, 861.     

Zur Kennzeichnung von Lorentztransformationen in Endlichen Ebenen

Given a commutative field K we define d(A,B):= (a₁–b₁)²–(a₂–b₂)² for A=(a₁,a₂), B=(b₁,b₂) K². Given moreover a fixed k K^O, W. Benz has asked for all mappings : K²K² such that d(A,B)=k implies. This paper gives an answer if K=GF(p), p=5,7,11: must be a bijective collineation in case p = 7,11; there are non-injective mappings in case p=5. To obtain some of these results we have mads use of a computer.

---

---

Prof. R. Artzy zum 70. Geburtstag gewidmet.     

On strong summability of multiple Fourier series and smoothness properties of functions

_n —n- — ƒ()L _v (T _n ), 1f, - -. -.     

Configurationally and conformationally homogeneous cyclic n-aryl sulfimides—IV : Synthesis,configuration and stereochemistry of the rearrangement of 1,3-di-thiane-1-N-p-chlorophenylimides

1,3-Dithiane-1-N-p-chlorophenylimides (1,4-9) were prepared and their configuration and conformation was determined by ¹H and ¹³C NMR. The compounds were rearranged to the corresponding 2-(2'-amino-5'-chlorophenyl)-1, 3-dithianes (1U,4U,9U). The rearrangement reactions took place with ?95% stereospecifity. The mechanism of the reaction was investigated with the aid of analogs specifically deuterated at C-2.