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The aminolysis of the hexachlorocyclotriphosphazene, N3P3Cl6 1, by the oxodiamines H2N-(CH2)3-O(CH2)2-O-(CH2)3 NH2 2 and H2N-(CH2)3-O-(CH2)6-O-(CH2)3-NH2 3 occurs immediately and regiospecifically in dry media leading to the corresponding spiranic cryptands 4 and 5, respectively. This process is an actual improvement (time, selectivity and workup) on the standard reactions.

The reaction of N3P3Cl6 with 4,11-dioxatetradecane-1,14-diamine (designated 3O6O3) in a heterogeneous medium (interface process) of toluene and saturated aqueous Na2CO3 leads stereoselectively to a trans monocyclophosphazene 19-crown-ether species (trans MACRO-ANSA 3O6O3) which crystallizes in the monoclinic system, P21/n a=8.539(2), b=8.997(3), c=30.123(4) A, β=91.65(2)°, V=2313(2) A3, Z=4, Dx=1.456 Mg m−3, R=0.054 for 2826 unique reflections and 236 variable parameters. The structure exhibits a spatial arrangement with one [HN-(CH2)3-O-(CH2)6-O-(CH2)3-NH] as an arch, grafted in a trans configuration onto two different phosphorus atoms (trans non-gem disubstitution) of one N3P3Cl4 moiety. This fortuitously discovered trans-19-crown-ether-shaped macrocyclic structure defies the well-established description of the electronic structure of six-membered cyclophosphazene rings.

The aminolysis of the hexachlorocyclotriphosphazene, N3P3Cl6 1, by the oxodiamines H2N-(CH2)3-O(CH2)2-O-(CH2)3 NH2 2 and H2N-(CH2)3-O-(CH2)6-O-(CH2)3-NH2 3 occurs immediately and regiospecifically in dry media leading to the corresponding spiranic cryptands 4 and 5, respectively. This process is an actual improvement (time, selectivity and workup) on the standard reactions.

The reaction of N3P3Cl6 with 4,11-dioxatetradecane-1,14-diamine (designated 3O6O3) in a heterogeneous medium (interface process) of toluene and saturated aqueous Na2CO3 leads stereoselectively to a trans monocyclophosphazene 19-crown-ether species (trans MACRO-ANSA 3O6O3) which crystallizes in the monoclinic system, P21/n a=8.539(2), b=8.997(3), c=30.123(4) A, β=91.65(2)°, V=2313(2) A3, Z=4, Dx=1.456 Mg m−3, R=0.054 for 2826 unique reflections and 236 variable parameters. The structure exhibits a spatial arrangement with one [HN-(CH2)3-O-(CH2)6-O-(CH2)3-NH] as an arch, grafted in a trans configuration onto two different phosphorus atoms (trans non-gem disubstitution) of one N3P3Cl4 moiety. This fortuitously discovered trans-19-crown-ether-shaped macrocyclic structure defies the well-established description of the electronic structure of six-membered cyclophosphazene rings.

Aminolysis of hexachlorocyrocyclotriphosphazene, N3P3Cl6, by the spermine-like derivative coded as SPM (323), namely N,N′-bis-(3-aminopropyl)-ethylendiamin H2N-(CH2)3-NH--(CH2)2-NH-(CH2)3-NH2, yields regiospecifically either to the DISPIRANSA or to the DISPIRBINO moiety depending on which chemical is used as the yin reactant. Indeed, if N3P3Cl6 is added as the yang active reactant to the tetramine as the yin passive receptor, the former configuration is obtained whereas the the latter proceeds from an addition of the tetraamine as the yang active reactant on the N3P3Cl6 as the yin receptor.

Since the polyamine metabolism system is very active in proliferative glioma cells, polyamine linked drugs are to be considered as potential antineoplastic agents against malignant gliomas. This study reports the trial of a new compound lineage, the Polyamine Linked Cyclophosphazenes, on human glioblastoma heterografts in nu-nu mice. Two agents are tested: DIAM 3 and DIAM 4. Both show an important antineoplastic action either on a chronic treatment schedule or as single dose. Systemic tolerance is satisfactory.

MRL-lpr/lpr mice develop T cell lymphadenopathy, polyclonal activation of B lymphocytes, autoantibodies and lupus nephritis. B and T cell populations, the dysfunctions of which play a role in the pathophysiology of the mouse disease, represent potential targets for lupus treatment. MRL-lpr/lpr mice are treated from the age of 19 weeks, i.e. after the onset of renal disease and lymphoproliferation, with Cyclosporin A which acts at the T cell level, or with DIAM4 which can down modulate polyclonal activation of B lymphocytes. DIAM4 induces the disappearance of the lymphoproliferation, the increase in C3 levels and the decrease in anti-DNA antibody, immunoglobulin and urea levels, and proteinuria. Cyclosporin A reduces lymph node hyperplasia, but has no effect on other parameters of the disease.

Singly, doubly and triply bridged polyazaheterophanes (1,2,3) have been synthesized from hexachlorocyclotriphosphazene, N3P3Cl6. 31P NMR spectra indicate that the molecules 2 exist in a single conformation when there are three differently populated conformations A, B and C, in molecules 3 at ambient temperature, A and (B + C) being separated by a high interconversion barrier (about 22 Kcal mole−1) whereas the barrier between B and C is much lower (about 4 Kcal mol−1).

The semi-empirical CNDO and INDO methods are applied to a theoretical conformational analysis of biaziridyl. In agreement with infrared and electron diffraction data, this molecule is found to be in its s-trans conformation. The origins of such a conformation are discussed in terms of Fourier developments. The prediction that some alterations of angles occur when going from the s-trans to the s-cis form, arises from these calculations.

The electronic structures of the various conformations and allotropic species of two promising anticancer drugs, namely MYKO 63 and SOAz, have been calculated using the CNDO/2 approximation. The results allow prediction of the acidity (in the Lewis sense) of the aziridinyl-bearing atoms of the drugs which corresponds to the optimum anticancer activity possible upon coordination to DNA, as the Lewis-base target.

Resume The conformational analysis and the electronic structure of t-butyl cyclopropyl ketones are investigated within the framework of the CNDO/2 approximation; in every case, the cis isomer is found to be preferred with an unusual conformation of the substituent with respect to the cyclopropane ring. Interaction between the oxygen of OH or OCH 3 substituents and the carbonyl oxygen atom is observed.

Cet article passe en revue l'ensemble complet de preuves structurales concluantes obtenues recemment en faveur de la configuration SPIRO lorsque N 3 P 3 Cl 6 reagit avec des diamines naturelles (propanediamine-1,3 et putrescine) et autres derives biogenes tels que la spermidine et la spermine sous conditions stoechiometriques

Etude, a l'aide de facteurs geometriques ou electroniques, de l'existence des 3 conformations SPIRO observees pour obtenir des antitumoraux plus selectifs a partir des structures RX

A quantitative evaluation of the Cossee mechanism is performed on the TiMeCl 3 · C 2 H 4 system. Differential electron density contours maps are found to be more reliable than HOMO electron density maps for the description of ethylene insertion into the TiC bond. Cossee's “φ RM ” assumption appears to be valid in this case while the “π-back bonding” formulation seems improbable. The existence of a “four centre intermediate” is related to the magnitude of the activation barrier to insertion.

(Theoretical conformational analysis and anti-depressive effectiveness of new bifunctional cyclopropanic derivatives: Midalcipran and relatives) The conformational analysis of Midalcipran, a novel anti-depressor agent, was achieved through a concerted use of the CNDO/2 quantum technique and of some new specific software for micro-computers, such as APPLE ///, which are able to design and sort preferred conformations. The anti-depressive activity is then attributed to the existence in the molecule of a “double-locked” rigid lactamic pattern highly suitable for receptor recognition.

An overall survey of 31 P NMR data for more than twenty B.A.S.I.C. ( B INO A NSA S PIRO i n C yclophosphazenes) systems reveals transferable chemical shift moduli characterizing basic bricks, i.e. BINO bridge, ANSA arch and SPIRO loop. These moduli are linearly related to the plus or minus T d -character of corresponding phosphorus atoms and such linear relationships allow some predictions about geometries of new B.A.S.I.C. systems X-ray structures of which are still unknown.

The spermine-linked innate DISPIRBINO configuration is commonly obtained by adding spermine to hexachlorocyclotriphosphazene, N 3 P 3 Cl 6 . Conversely, addition of N 3 P 3 Cl 6 to spermine in 1:2 stoichiometry and high dilution conditions in CHCl 3 yields a new merged DISPIRANSA structure cleanly, in a few hours at room temperature. The same architecture is also obtained when the spermine-like compound, i.e. H 2 N(CH 2 ) 3 NH(CH 2 ) 2 NH(CH 2 ) 3 NH 2 , is reacting on N 3 P 3 Cl 6 in the same conditions.

The electronic structure and preferred conformations of F3P·BH3 and F2HP·BH3 are investigated in the framework of the CNDO/2 approximation. In complete agreement with microwave data, the staggered conformations are predicted to be the most stable ones. The barriers to internal rotation are in good agreement with experimental values (F3P·BH3: calc. = 3.03 kcal/mole, exp. = 3.24 ± 0.15 kcal/mole; F2HP·BH3: calc. = 3.63 kcal/mole, exp. = 4.05 ± 0.45 kcal/mole) and a bicentric energy partitioning shows that the variations of the total energy are completely reflected by the only variation of the interaction energy between phosphorus and H atoms bonded to boron. The analysis of the electron densities reveals the importance of the 3s(P) → 2px(B) transfer in the formation of the co-ordination. Finally, the computed dipole moment value and direction agree with corresponding experimental data.

The magneto-optical behaviour of some strobilic compounds in solution in different solvents is described. The strobilic character vanishes when the electric polarisabilities of solute and solvent are equal, and in such cases the magnetic properties of the strobilic compounds are independent of concentration. An “equi-polarisable solvents” technique is proposed.

Resume L'etude, au moyen de la methode CNDO/2, de la molecule H 3 P·BH 3 et de ses derives perfluores permet de proposer pour chacun de cesedifices une geometrie moleculaire optimisee. Celle-ci s'avere, dans le cas de la molecule F 3 P·BH 3 , en parfait accord avec les donnees de la spectroscopie micro-ondes, et cet accord se poursuit au niveau de tous les parametres conformationnels etelectroniques caracteristiques de cette molecule. Par contre, dans le cas de H 3 P·BH 3 , on montre que la geometrie theorique optimisee differe notablement des modeles construits anterieurement sur des bases essentiellement intuitives. Toutes les moleculesetudiees se caracterisent par une conformation privilegiee decalee . L'amplitude des barrieresala rotation est discutee el leur origine interpretee. Les transferts de charge accompagnant l'edification du complexe sont calcules et s'averent en bon accord avec ceux provenant de travaux non empiriques recents. L'existence chimique des quatre molecules de la serie est enfin discutee.

Resume Le formalisme semi-empirique de la methode CNDO/2 est appliqueal'analyse de la structureelectronique et de la conformation de la molecule S2F10. Sur le plan conformationnel, un excellent accord est obtenu entre theorie et experience, le calcul permettant en outre de degager les facteurselectroniques qui definissent la courbe de potentiel caracterisant le systeme lors de la mise en rotation mutuelle des deux motifs SF5 autour de la liaison (S-S). Par ailleurs sont discutes le probleme de la nonequivalenceelectronique des atomes de fluor axiaux etequatoriaux, la signification des indices de Wiberg, la force des liaisons chimiques et la longueur ≪anormale≫ de la liaison (S-S) dans S2F10.

CONTENTS I. Introduction 346 II. What is the Faraday effect? 346 III. Experimental arrangement and accuracy of measurements 347 IV. The Faraday effect and the additive properties of matter 348 V. Magneto-optical investigation of conjugation phenomena 351 VI. The Faraday effect and three-dimensional conjugation 356 VII. Donor–acceptor σ bonds 357 VIII. Donor–acceptor (σ + π) bonds 359 IX. The Faraday effect and conformational analysis 362 X. The Faraday effect and the study of non-isolated complexes in solution 363 XI. The Faraday effect and Van Vleck ferromagnetism 363

The conformational analysis of methylcyclopropane, cyclopropylamine and cyclopropylphosphine is investigated within the framework of the CNDO/2 and INDO approximations. The preferred conformations-experimentally detected by microwave spectroscopy-are correctly predicted. Good agreement is obtained between the calculated and the measured values of rotational barriers, torsional potentials and dipole moments.

A SCF-LCAO-MO calculation, carried out on cyclopropylcarboxaldehyde (I), cyclopropyl-methylketone (II) and cis and trans-2-methylcyclopropylmethylketones (III and IV) (Chart 1) shows that (a) I, II and IV are only in s-cis and s-trans conformations, the s-cis form being favoured over the s-trans by 0-8 kcal/mole for I and by 1·6 kcal/mole for II and IV; (b) molecule III, of cis configuration, exists in s-cis and gauche conformations (Chart 10) with the former very predominant.

C 4 H 10 Cl 4 N 5 OP 3 cristallise dans Pnma avec affinement jusqu'a 0,039. HN-(CH 2 ) 2 -O-(CH 2 ) 2 -NH est porte sur deux atomes de phosphore de l'heterocycle mineral

Quantum mechanical calculations for a number of cyclophosphazenes reveal that transannular bonding and antibonding interactions contribute considerably to the stability and conformation of these PN ring systems. Charge distributions are only in agreement with the island theory; the latter is confirmed by Faraday effect measurements.

Die Ansa-Verbindung (I) reagiert mit IJ-Diaminopropan zu dem Spiroansacyclotriphosphazen (II), dessen verbliebener labiler Chloridsubstituent mit Diaminohexan zu dem neuen Verbindungstyp Dispirodiansabino-cyclotriphosphazen (III) reagiert.

The importance of d-orbital participation and of π-back-donation in phosphorus oxyfluoride is discussed through the results of ab initio SCF–MO calculations.

The electronic structures of the various conformations and allotropic species of two promising anticancer drugs, namely MYKO 63 and SOAz, have been calculated using the CNDO/2 approximation. The results allow prediction of the acidity (in the Lewis sense) of the aziridinyl-bearing atoms of the drugs which corresponds to the optimum anticancer activity possible upon coordination to DNA, as the Lewis-base target.

The influence of an antitumoral drug, the pentaziridinocyclodiphosphatiazene (SOAZ), on the right----left-handed helix conformational transition of Poly (dG-dC). Poly (dG-dC) induced by carcinogenic or mutagenic Nickel compounds has been studied by ultraviolet absorbance and circular dichroïsm measurements. The B----Z transition of the polynucleotide is induced in two steps, in a similar way whatever the origin of the Nickel ions (NiCl2, NiSO4, Ni3S2, NiCO3). The midpoint of the second step (right----left-transition) is located around 0.4 mM Ni2+. The addition of SOAZ to the Poly (dG-dC). Poly (dG-dC) modifies this transition which is shifted to 2 mM Ni2+ for a 1 SOAZ/10 DNA phosphates ratio. The right-handed helix is stabilized and for a 1.5 SOAZ/phosphate ratio no B----Z transition is observed even for a tenfold amount of added Nickel (4 mM Ni2+). The addition of SOAZ to the DNA initially converted to a Z conformation by the presence of Nickel inhibits the return to the B form.

The antineoplastic activity of hexaziridinocyclotriphosphazene (Myko 63) has been investigated in a panel of murine ascitic and solid tumors. Myko 63 was found to significantly retard primary and secondary tumor growth and to prolong the survival rates in each of the nine models employed. These included the L1210 and P388 leukemias, P815 mastocytoma, the 3LL and Madison 109 carcinomas, M5076 reticulum cell sarcoma, the line 26 colon and line 16 mammary carcinomas, and an intracranially implanted ependymoblastoma. The possible modes of action of this compound and the potentials of cyclophosphazenes, a chemical class largely unexplored as antitumor agents are discussed.

Mass spectrometry has been used for testing the chemical purity of some new antitumor cyclophosphazene compounds. the spectrum of N3P3Az6 (code name MYKO 63)--which exhibits noticeable activity on murine P 388, L 1210 and B 16 tumors--appeared to be remarkably simple, as most of the fragmentations arose from successive losses of the aziridino radicals. Traces of the pentaziridinomonochloro impurity formed by an incomplete substitution of N3P3Cl6 chlorine atoms under aziridinolysis could be detected in an impure and toxic sample by spectral subtraction. Quantification of this impurity was performed by selected ion monitoring in the direct inlet mode of sample introduction. The mass spectra of other derivatives of this class of compounds are slightly more complex, since the decomposition pathways showed more intense H-transfers associated with the loss of substituents.

In 196 cases of gastro-oesophageal reflux, simple or connected to a hiatal hernia or to a cardio-tuberous misplacement, the respiratory signs that are found in 1 patient out of 4, are analyzed. The nocturnal fits of coughing (39 cases, 20% of the reflux) is the most frequent sign of laryngo-tracheal aspiration of stomach content. This symptom of great diagnostic value, though neglected, should be looked for systematically. Other troubles are less frequent: bouts of recurring broncho-pulmonary infections, asthma attack, Mendelson's syndrome, pulmonary fibrosis. In absence of a patent cause, the symptoms should lead to suspect a reflux of stomach content in the airways. Similarly to oesophagitis, respiratory signs represent a complication sometimes serious, of gastro-oesophageal reflux, needing more frequently a surgical treatment of hiatal herniae or of the cardiac inefficiency.

Singly, doubly and triply bridged polyazaheterophanes (1,2,3) have been synthesized from hexachlorocyclotriphosphazene, N3P3Cl6. 31P NMR spectra indicate that the molecules 2 exist in a single conformation when there are three differently populated conformations A, B and C, in molecules 3 at ambient temperature, A and (B + C) being separated by a high interconversion barrier (about 22 Kcal mole−1) whereas the barrier between B and C is much lower (about 4 Kcal mol−1).