Labelling of Carbaboranyl Compounds with a Selenium Atom with a View to Applications in Boron‐Neutron‐Capture Therapy (BNCT) and Positron‐Emission Tomography (PET)

We synthesized 2′‐carbaboranyl‐2,5′‐bi‐1H‐benzimidazoles containing 10 B‐atoms and labeled with Se or the positron‐emitting radionuclide ⁷³Se (t_1/2=7.1 h), with a view to their application to cancer treatment by boron‐neutron‐capture therapy (BNCT) and to compound‐distribution measurements in vivo by positron‐emission tomography (PET). Thus, 2,2′‐{{2′‐{4‐[1,2‐dicarba‐closo‐dodecaboran(12)‐2‐ylmethoxy]phenyl}‐[2,5′‐bi‐1H‐benzimidazol]‐5‐yl}imino}bis[ethanol] ( 26c ) was obtained by the reaction of 2,2′‐[(3,4‐diaminophenyl)imino]bis[ethanol] ( 19 ) with ethyl 2‐{4‐[1,2‐dicarba‐closo‐dodecaboran(12)‐2‐ylmethoxy]phenyl}‐1H‐benzimidazole‐5‐carboximidate hydrochloride ( 25 ), as well as the analogues 26a and 26b (Scheme 6). Tosylation of compound 26c gave 4 regioisomers 27a – d , which, after selenation, produced 2′‐{4‐[1,2‐dicarba‐closo‐dodecaboran(12)‐2‐ylmethoxy]phenyl}‐5‐(tetrahydro‐2H‐1,4‐selenazin‐4‐yl)‐2,5′‐bi‐1H‐benzimidazole ( 29 ) in 42% yield (Scheme 7).     

Electrostatic medium effects and formal quantum structure–activity relationships in apomorphines interacting with D1 and D2 dopamine receptors

The binding of apomorphines (AM) to D₁ and D₂ dopamine receptors is analyzed through a formal quantum structure–activity relationship method. The calculations were carried out at the CNDO/2 level of the molecular orbital theory with a continuum representation of environmental effects. The results show that the D₁ receptor affinity variation is related to the variation of the electron-donating capacity of a C atom of the hydroxylic region of apomorphines in a low-polarity medium. The N-chain probably interacts with a hydrophobic region of the receptor. It is also concluded that the poor results for the D₂ binding affinity are explained by errors in the experimental measurements. Finally, it is proposed that future structure–activity relationship studies must be carried out for media of different polarities. © 1997 John Wiley & Sons, Inc.     

Thiolate-Bridged Diiron(III) Complex with Spin-Crossover Behaviour

The reaction of the ligand HL · (HCl)₂ (HL = 2,6-di(aminomethyl)-4-tert-butyl-thiophenol) with MCl₂ in methanol in the presence of sodium methanolate and air affords the dinuclear complexes [L₃M₂][ClO₄]₃ (M = Fe: 2 , Co: 3 ) in 85% and 68% yield, respectively. Both complexes were characterized by infrared spectroscopy, magnetic susceptibility measurements, and ¹H NMR spectroscopy. By temperature-variable ⁵⁷Fe Mössbauer spectroscopy diamagnetic 2 is shown to exhibit a gradual spin transition between the species [L₃(low-spin-Fe)₂]³⁺ ((ls,ls)- 2 ) and [L₃(high-spin-Fe)₂]³⁺ ((hs,hs)- 2 ). At room temperature the relative concentrations of both species are nearly equal. Well resolved quadrupole doublets at all temperatures for both (ls,ls)- 2 (γ in the range 0.22(1)–0.28(1) mm s^–1) and (hs,hs)- 2 (γ in the range 0.48(1)–0.53(2) mm s^–1) are indicative of a spin conversion time longer than the half-life of the I = ³/₂ state of ⁵⁷Fe. Cyclic voltammetry and square wave voltammetry of 2 in CH₃CN solution reveal four quasi-reversible one-electron transfer processes. The first two processes were assigned to metal-centered reductions of (hs,hs)- 2 and (ls,ls)- 2 , respectively, to yield the mixed-valent species [L₃Fe^IIFe^III]³⁺.     

Effects of Tributyltin(IV) Chloride Exposure on Larvae of Ciona intestinalis (Urochordata): An Ultrastructural Study

The effects of tributyltin(IV) chloride (TBT chloride) have been tested on embryos of the ascidian Ciona intestinalis , at two different stages of development: (1) before hatching (coiled larval stage) and (2) 2 h after hatching (swimming larval stage). In vivo observations carried out with a light microscope showed that embryos at the coiled larval stage did not hatch following exposure to TBT chloride. Severe anomalies in the swimming larva, mainly concerning the morphology of the tail, which appeared twisted and squatter than in the controls, were observed. Such anomalies were also found at a functional level, i.e. contractile movements were poor so that the larvae appeared motionless. Ultrastructural investigations carried out using a transmission electron microscope (TEM) evidenced that the muscle cells were damaged. Modifications mainly occurred in mitochondria and myofibrils, i.e. the energetic and enzymic centres. This fact is probably the main cause of the loss of mobility of the larvae.     

N‐(o‐Chloro­phenyl)‐2,5‐di­methyl­pyrrole‐3‐carb­aldehyde

Crystal structure analysis of the title compound, C₁₃H₁₂ClNO, reveals three crystallographically independent mol­ecules in the asymmetric unit. The main conformational difference between these mol­ecules is the orientation of the phenyl rings with respect to the pyrrole rings. The coplanar arrangement of the aldehyde groups attached to the pyrrole rings influences the pyrrole‐ring geometry. The C2—C3 and N1—C5 bonds are noticeably longer than the C4—C5 and N1—C2 bonds. Two independent mol­ecules of the title compound form dimers via intermolecular C—H⃛O hydrogen bonds [D⃛A = 3.400 (3) Å and D—H⃛A = 157°]. The perpendicular orientation of the phenyl and pyrrole rings of one independent mol­ecule and its symmetry‐related mol­ecule allows C—H⃛π interactions, with an H⃛centroid distance of 2.85 Å and a C—H⃛π angle of 155°. The distances between the H atom and the pyrrole‐ring atoms indicate that the C—H bond points towards one of the bonds in the pyrrole ring.     

Cyclophosphazenes as polymer modifiers

The utilization of Cyclophosphazenes as polymer modifiers is reviewed, with particular concern to their exploitation as versatile chain extenders, possibly for recycle problems, crosslinkers, to enhance mechanical properties of polymeric materials, branchers, to selectively introduce ramifications in linear polymers, and compatibilizers, to favor the formation of blends between originally incompatible organic macromolecules. The great versatility of the synthetic methods put forward for these substrates, together with the ease of controlling their modification, functionalization and reactivity are important parameters for the evaluation of which type of use is more feasible for these trimers. The importance of cyclophosphazenes bearing organic polymeric chains, azide groups, 2-oxazoline derivatives and oxirane rings in connection with organic conventional macromolecules is critically highlighted.     

Synthesis,Kinetics, and Molecular Docking of Novel 9‐(2‐Hydroxypropyl)purine Nucleoside Analogs as Ligands of Herpesviral Thymidine Kinases

In the context of broadening the knowledge on substrate specificity of Herpes simplex virus type 1 thymidine kinase (HSV‐1 TK) and Varicella‐Zoster virus thymidine kinase (VZV TK), new derivatives of 9‐(2‐hydroxypropyl)‐substituted adenine, chloropurine, hypoxanthine, guanine, thiopurine, and (methylsulfanyl)purine were synthesized and subjected to in vitro phosphorylation and binding affinity assays. The interactions between the compounds and the crystallographically determined active site residues of HSV‐1 TK have been studied by molecular modeling with the Lamarckian genetic algorithm of docking program AutoDock 3.0. All compounds mentioned bind to both enzymes in the low mM to sub‐mM range, comparable to binding affinities of existing prodrugs. Findings from the docking procedure indicate multiple binding modes for all of the compounds and are in accordance with the results of phosphorylation and binding‐affinity studies. Furthermore, the studies reveal that hypoxanthine derivatives represent a new class of TK substrates and thiopurine derivatives a new class of TK inhibitors.     

Dependence of flow behaviour of nematics in shear on the form of the mean-field potential

The dynamic transition of nematics in (slow) shear from flow-aligning to tumbling behaviour is here predicted by using the rigid rod-like molecular model together with an extension of the Maier-Saupe mean-field potential. Such an extension, already available in the literature with reference to equilibrium data, includes interactions of rank higher than the basic quadrupolar one considered by Maier and Saupe. The theoretical predictions are then compared with the few existing sets of dynamic data. Although an acceptable qualitative agreement is found, the theory generally overpredicts the value of the relevant ratio α₃/α₂ of Leslie coefficients.