Halogen bonding: a paradigm in supramolecular chemistry.

The term halogen bonding describes the tendency of halogen atoms to interact with lone pair possessing atoms. The binding features and structural properties of halogen bonding are discussed and applied to drive the intermolecular self-assembly of hydrocarbons and perfluorocarbons in chemo-, site-, and enantioselective supramolecular synthesis. The halogen bonding is thus an effective and reliable tool in crystal engineering at the disposal of the supramolecular chemist.

Interactions at the outside faces of calix

Attractive pi-pi interactions between two of the four outside cavity faces of 1,3-bis-pyridylmethylcalix[4]arene (1) and both faces of 1,4-diiodotetrafluorobenzene (2a) form infinite one-dimensional non-covalent ribbons where the two modules alternate. These ribbons are cross-linked by electron donor-acceptor interactions between picolyl nitrogen atoms of calixarene 1 in one chain and iodine atoms of perfluoroarene 2a in another chain and the two-dimensional supramolecular network 3a is formed. A similar behaviour is also shown by 1,4-dibromotetrafluorobenzene (2b). The halogen bonding and the attractive pi-pi interactions occur in directions which are nearly orthogonal each other. Diiodotetrafluorobenzene, being involved in both these interactions, appears to be a particularly interesting tecton. The ability of electron-poor arenes to elicit the exo-receptor potential of calixarene module by connecting their outside faces through pi-pi interactions may be developed as a new and general binding protocol in calixarene self-assembly processes.

Resolution of Racemic 1,2-Dibromohexafluoropropane through Halogen-Bonded Supramolecular Helices.

Halogen bonds, attractive intermolecular interactions between perfluoroalkyl bromides and bromide ions, are present in cocrystals of (-)-sparteinium hydrobromide (1) and (S)-1,2-dibromohexafluoropropane (2; shown schematically), and result in enantiopure and infinite supramolecular helices. The perfluorocarbon-hydrocarbon self-assembly allows the resolution of racemic 2.

Synthesis and evaluation of the antiviral activity of acyclic nucleosides carrying fluorine and sulfur substituents.

-2',3'-Seco nucleosides 5 carrying fluorine and sulfur substituents at C-3' and C-5', respectively, of acyclic sugar moiety were synthesized in enantiomerically and diastereoisomerically pure form. These products and some structurally similar 1',2'-seco-2'-nor-and 1',2'-seco-nucleosides 3 and 4 were tested in vitro for cytotoxicity and antiviral activity. At non-cytotoxic concentrations the compounds were inactive against human immunodeficiency virus and herpes simplex virus type-1.

Synthesis and pharmacological evaluation of enantiomerically pure 4-deoxy-4-fluoromuscarines.

Four isomers of [(4-fluoro-5-methyl-tetrahydrofuran-2-yl)methyl]trimethylammonium iodide (4-deoxy-4-fluoro-muscarines) were prepared in enantiomerically and diastereomerically pure form from (S)-(-)-methyl 4-methylphenyl sulfoxide, ethyl fluoroacetate, and allyl bromide. Their absolute configurations were assigned by 1H NMR analyses. The four optically pure compounds were tested in vitro on guinea pig and their muscarinic potency was evaluated at M3 (ileum and bladder) and M2 (heart) muscarinic receptor subtypes. Compound 1a, the most potent isomer of the series, was also tested in vivo on pithed rat and its muscarinic activity at the M1 receptor subtype was compared with that of muscarine. Moreover, affinity and relative efficacy were calculated in vitro for this compound at M2 (heart force and rate) and M3 (ileum and bladder) receptors in order to investigate muscarinic receptor heterogeneity. The 4-deoxy-4-fluoromuscarines display a similar trend of potency as the corresponding muscarines and compound 1a shows differences in the affinity constants among the studied tissues. Replacement of a hydroxyl group for a fluorine atom in the 4 position of muscarine produces 1 order of magnitude increase in affinity for cardiac M2 muscarinic receptors controlling rate, while the affinity at cardiac M2 muscarinic receptors controlling force is unchanged, opening the possibility of a further classification of cardiac muscarinic receptors.

Fast-atom bombardment mass spectrometry and metastable-ion studies for the characterization of isomeric fluorosugars.

Characterization of stereoisomeric 3,4-dideoxy-3-fluoro-hexoses has been carried out using fast-atom bombardment. Diagnostic fragments were observed in the daughter-ion spectra of the [M - H]- and [M + H]+ ionic species. Notable differences were also observed in the relative abundances of ionic species corresponding to [M - H]-, [M - H - HF]- and [C11H11O2]- ions.

Novel pyrimidine and 1,3,5-triazine hypolipidemic agents.

New compounds were synthesized by changing the substituents of a trisubstituted pyrimidine, i.e., [[4-chloro-6-[(2,3-dimethylphenyl)amino]-2-pyrimidinyl]thio] acetic acid, a potent hypolipidemic agent, impaired, however, by a marked hepatomegaly-inducing effect. The structural variations led to the subsidence (14b, i.e., 4-chloro-2-(dimethylamino)-6-[(2,3-dimethylphenyl)amino]pyrimidine) or to the reduction (18b, [[4-chloro-6-[(2,3-dimethylphenyl)amino]-2-pyrimidinyl]amino] acetic acid) of said untoward effect but still maintained the hypolipidemic effect that, although markedly decreased, still proves significant for serum cholesterol and triglycerides (18b) or for serum triglycerides only (14b).

Synthesis of new 2-(2-phenylethenyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine-7-carboxylic acids.

New 2-(2-phenylethenyl)-4-oxo-4H-pyrido[1,2-a]pyrimidine-7-carboxylic acids with a hydroxy or alkoxy substituent in the 3-position were synthesized as potential antiallergic agents. None of them was effective in passive cutaneous anaphylactic reaction test in the rat.

Synthesis of 2-carboxy-11 beta, 17 beta-dihydroxy-17-methyl-1, 4-androstadien-3-one and related compounds.

A series of 2-carboxy-1, 4-androstadien-3-one derivatives and their alkyl esters, were prepared by high-yield syntheses. The compounds were structurally identified by physical methods. All these steroids are characterized by a marked antiglucocorticoid activity that proved long-acting in the case of the ester derivatives. 2-Carboxy-11 beta, 17 beta-dihydroxy-17-methyl-1, 4-androstadien-3-one or roxibolone, and its n-decylester or decylroxibolone, are the most promising derivatives in consideration of their pharmacological properties.