Gerasimos M. Tsivgoulis

1,2-DIHYDROXYPROPYL-3-ARSONIC ACID: A KEY INTERMEDIATE FOR ARSONOLIPIDS

Abstract The synthesis and properties of a key intermediate for arsonolipids, rac-1,2-dihydroxypropyl-3-arsonic acid and its salts, are described. The mechanism of the Meyer reaction with β-hydroxy alkyl halides is discussed.

SYNTHESIS OF (R)- AND (S)-1,2-DIACYLOXYPROPYL-3-ARSONIC ACIDS: OPTICALLY ACTIVE ARSONOLIPIDS

Abstract Reaction of trisodium arsenite with (R)- and (S)-glycidol affords in good yields the (R)- and (S)-1,2-dihydroxypropyl-3-arsonic acid, the tetrabutylammonium salt of which upon acylation with myristic, palmitic and stearic anhydrides in the presence of pyridine gives, in moderate to low yields, optically active arsonolipids, i.e., (R)- and (S)-1,2-diacyloxypropyl-3-arsonic acids. The thermotropic phase transitions of these arsonolipids are characterized. Results show that the transition temperatures and enthalpies of fusion of the racemates are lower than those of the enantiomers in the powder form presumably because of conglomerate formation. The thermotropic transition characteristics of the aqueous dispersions of the arsonolipids change with the acyl chain lengths, and the overall behaviour is similar to that of the aqueous dispersions of phospholipids.

rac-1,2-diacyloxypropyl-3-arsonic acids arsonolipid analogues of phosphonolipids

Abstract A new class of lipids, arsonolipids or rac-1,2-diacyloxypropyl-3-arsonic acids, have been synthesized by acylating tetrabutyl ammonium hydrogen rac-1,2-dihydroxypropyl-3-arsonate with myristic, palmitic and stearic anhydrides in the presence of pyridine. The yields are moderate to low due to decomposition of rac-1,2-dihydroxypropyl-3-arsonic acid and its salts by acylating agents. Acid salts of arsonolipids were prepared by neutralization but neutral salts could not be made.

The Oxidation of Trialkyl Trithioarsenites, (RS)3As, by Octasulfur/Triethylamine and Dioxygen

Trialkyl trithioarsenites, (RS) 3 As, bearing terminal carboxy (─COOH) or carboxylate (─COO−Na+) or zwitterionic (─CH(NH 3 +)COO−) groups were studied for their ability to be oxidized by octasulfur, S 8 , and by dioxygen. The carboxy-bearing trithioarsenites are not oxidized by S 8 to the corresponding As(V) esters, (RS) 3 As=S, probably because they cannot open the octasulfur ring, but they react with S 8 in the presence of triethylamine, which acts as an activator of S8. The carboxylate-bearing trithioarsenites, however, do react under drastic conditions with S 8 . In both cases colored insoluble solids were obtained which could not be characterized. The carboxy-bearing trithioarsenites are oxidized by air in a hydrocarbon chain-length depended manner, while the carboxylate-bearing trithioarsenites are not, if at all, oxidized by air to arsenic(III) oxide, As 2 O 3 , and disulfide, RSSR. The zwitterion-bearing tris(penicillamine), tris(cysteine), and tris(glutathione) trithioarsenites are air oxidized slower than their corresponding parent thiols and this may be of biochemical significance.

Synthesis and characterization of soluble, blue-fluorescent polyamides and polyimides containing substituted p-terphenyl as well as long aliphatic segments in the main chain

A novel class of semiflexible polyamides and polyimides bearing substituted p-terphenyl as well as long aliphatic segments in the main chain were synthesized through pyrylium salts. Characterization of polymers was accomplished by inherent viscosity, elemental analysis, FT-IR, NMR, UV-vis luminescence spectroscopy, X-ray analysis, differential scanning calorimetry, thermomechanical analysis, thermogravimetric analysis, isothermal gravimetric analysis, and water uptake measurements. Polyamides displayed a degree of crystallinity and dissolved in polar aprotic solvents containing lithium chloride, as well as in trichloroacetic acid. Polyimides were amorphous and showed an excellent solubility, being soluble in various common solvents. The solutions of polyamides in DMF were blue-fluorescent with maxima at 362-370 nm. The emission maxims were not influenced appreciably upon the structure of the pendent groups and the length of the aliphatic spacers of backbone. The polymers possessed T(g)s at 98-131 degrees C and exhibited a satisfactory thermal stability

ON THE BEHAVIOUR OF SULFONATES TOWARDS AS(III) NUCLEOPHILES

Abstract Mesylates and hydrophilic amsylates and [3]betylates were tried as substrates in an effort to create a C-As bond. In no case did we detect the formation of arsonic acids. With Na3AsO3 as nucleophile the product was the parent alcohol due to exclusive attack of the HO present in the aqueous Na3AsO3. With (PhS)3As as the nucleophile in the absence of Lewis acid catalyst the products were diphenyl disulfide and As2O3 while in the presence of catalyst alkyl phenyl sulfide was obtained, implying that the electron pair on As was chemically inactive. As2O3 did not react with these electrophiles, and potassium di-O-phenylenedioxyasenate(III) was unreactive towards alkyl bromides but it gave the monoalkyl ether of catechol with amsylates and [3]betylates, again implying that the stereochemically active electron pair of As was not chemically active.

Photochromism of Dithienylethene Derivatives Trapped in Sol-Gel Matrices

Abstract Solid-state materials containing photochromic dithienylethene derivatives were prepared by the sol-gel process in the form of thin films of a few μm-thick. The effect of substituents (pyridyl or methoxyphenyl) of the optically active molecules on photochromic properties was investigated. Thicknesses and refractive indices either at 633 nm or 785 nm were determined in the colored and in the discolored state by using the Attenuated Total Reflexion method. Sol-gel films containing methoxphenyl substituted molecules show a large refractive index change, Δn=3.10−3 at 785 nm. This variation is important considering the low doping level (0.7 wt%).

DECOMPOSITION OF ALKYLARSONIC ACIDS BY ACYLATING AGENTS

Abstract Benzylarsonic acid is decomposed by palmitoyl chloride. slowly in the absence and rapidly in the presence of pyridine, giving benzyl chloride. Benzylarsonic acid is decomposed by palmitic anhydride in the presence, but not in the absence, of pyridine giving benzyl palmitate and benzyl pyridinium cation.

Design and synthesis of multifunctional phospholipids

Abstract The synthesis of a bifunctionalized phosholipid capable of binding streptavidin or poly-histidine-tagged proteins is reported for the first time. The head group containing both a biotin and an NTA chelator is synthesized via a new approach using solid phase synthesis.

A novel synthetic luteinizing hormone-releasing hormone (LHRH) analogue coupled with modified β-cyclodextrin: insight into its intramolecular interactions.

BACKGROUND Cyclodextrins (CDs) in combination with therapeutic proteins and other bioactive compounds have been proposed as candidates that show enhanced chemical and enzymatic stability, better absorption, slower plasma clearance and improved dose-response curves or immunogenicity. As a result, an important number of therapeutic complexes between cyclodextrins and bioactive compounds capable to control several diseases have been developed. RESULTS In this article, the synthesis and the structural study of a conjugate between a luteinizing hormone-releasing hormone (LHRH) analogue, related to the treatment of hormone dependent cancer and fertility, and modified β-cyclodextrin residue are presented. The results show that both the phenyl group of tyrosine (Tyr) as well as the indole group of tryptophan (Trp) can be encapsulated inside the cyclodextrin cavity. Solution NMR experiments provide evidence that these interactions take place intramolecularly and not intermolecularly. CONCLUSIONS The study of a LHRH analogue conjugated with modified β-cyclodextrin via high field NMR and MD experiments revealed the existence of intramolecular interactions that could lead to an improved drug delivery. GENERAL SIGNIFICANCE NMR in combination with MD simulation is of great value for a successful rational design of peptide-cyclodextrin conjugates showing stability against enzymatic proteolysis and a better pharmacological profile.