Norberto Farfán

New macrocyclic oligoboronates

Abstract Two new macrocyclic oligoboronates were prepared in easy one step syntheses from aminodialcohols and phenylboronic acid. Reaction of 2,6-pyridinedimethanol gives a tetrameric species, while 2-(salicylideneamino)-1-hydroxyethane provides a cyclobisboronate. Both compounds are characterized by using X-ray structural analyses. Possible applications in the supramolecular host-guest chemistry are discussed.

Phospholipid Membranes Form Specific Nonbilayer Molecular Arrangements That Are Antigenic

Hexagonal phase (HII)-preferring lipids such as phosphatidate, cardiolipin, and phosphatidylserine form nonbilayer molecular arrangements in lipid bilayers. While their presence in biological membranes has not been established, in vitro studies suggest that alterations in membrane properties modify their function. In this study, antiphospholipid monoclonal antibodies were developed against nonbilayer structures. One of the monoclonal antibodies identifies nonplanar surfaces in liposomes and in membranes of cultured cells. These results are the first evidence that natural membranes maintain a fragile balance between bilayer and nonbilayer lipid arrangements. Therefore, these antibodies can be used to evaluate the role of HII-preferring lipids in the modulation of membrane activities. Our studies demonstrated that nonplanar surfaces are highly immunogenic. Although these structures are normally transient, their formation can be stabilized by temperature variations, drugs, antibiotics, apolar peptides, and divalent cations. Our studies demonstrated that abnormal exposure of nonbilayer arrangements may induce autoimmune responses as found in the antiphospholipid syndrome.

NMR and X-ray diffraction studies of two bicyclic borates containing chiral boron and nitrogen atoms

Abstract Ring closure between the nitrogen and boron atoms during the syntheses of bicyclic organoboron compounds occurs under asymmetric induction, since reactions of optically active N-methyl-N-(1-methyl-2-phenyl-2-hydroxyethyl)glycines with 4-bromophenylboronic acid or with 1,4-phenylenediboronic acid provides the corresponding bicyclic boron derivatives (N → B)-4-bromophenyl[N-methyl-N- (1-(S)-methyl-2-(R)-phenyl-2-oxyethyl)aminoacetate-O,O′,N]boron (3a–3b), (N → B)-4-bromophenyl[N-methyl-N-(1-(S)-methyl-2-(S)-phenyl-2-oxyethyl)aminoacetate-O,O′,N]boron (4a–4b), (N → B)(N′ → B′)-1,4-phenylenebis[N-methyl- N-(1-(S)-methyl-2-(R)-phenyl-2-oxyethyl)aminoacetate-O,O′,N]bis-boron (5) and (N → B)(N′ → B′)-1,4-phenylenebis[N-methyl-N-(1-(S)-methyl-2-(S)-phenyl-2-oxyethyl)aminoacetate-O,O′,N]bisboron (6) in high stereochemical yields. The configuration of the nitrogen and boron atoms in 6 and in (N → B) phenyl[N-methyl-N-(1-(S)-phenyl-2-oxyethyl)aminoacetate-O,O′,N]boron (2) is established by single crystal X-ray diffraction studies.

Boron-nitrogen macrocycles: a new generation of calix[3]arenes.

The simple condensation reaction of 3,5-di-tert-butyl salicylaldehyde and 3-aminophenylboronic acid leads to a trimeric macrocyclic compound. The ability of this molecule to include small organic molecules was in a first approximation analyzed by (1)H NMR spectroscopy and X-ray crystallography.

NMR study of the effect of nitrogen-borane coordination on the conformational equilibrium of six membered ring heterocycles.

Abstract The syntheses, conformational and spectroscopic studies of N-borane adducts of 14 nitrogen containing six-membered ring heterocycles are reported. It was found that borane can act as a conformational and configurational locking agent. In addition, it can be very helpful for the assignment of the chemical shifts of other atoms or groups in the molecule as well as to ascertain the configuration at substituted carbons.

Study of cyclic borinates obtained from piperidine- and piperazine alcohols by spectroscopic methods and X-ray crystallography

Abstract A series of eleven new 2-aminoethyl- and 3-aminopropyl borinate derivatives with a coordinative N→B bond has been synthesized by condensation reactions between piperidine- as well as piperazine alcohols and diphenylborinic acid. The products obtained are analogous to N-spiro compounds and bicyclic systems and have been characterized by spectroscopic methods and X-ray crystallography. Thereby the N→B bond and the geometry of this new heterocyclic systems have been studied in more detail.

Reversible and irreversible inhibitory activity of succinic and maleic acid derivatives on acetylcholinesterase

Aryl succinic and maleic acid derivatives are potent inhibitors of bovine acetylcholinesterase in vitro. Succinic acid aminophenol derivatives 1b-e and 2b-d act as reversible inhibitors of acetylcholinesterase, while maleic acid aminophenol derivatives 3b-d and 4c-e act as choline subsite-directed irreversible inhibitors, detected by dialysis in the presence of edrophonium. Linear relationships between the logarithm of the velocity of hydrolysis of acetylcholine plotted against the time of incubation at several different inhibitor concentrations were determined. The K(i) for reversible competitive inhibitors was determined. For irreversible inhibitors the K(i) for the dissociation constant of the enzyme-inhibitor complex at the beginning of the recognition process was also determined as well as the inactivation constant of the enzyme-inhibitor adduct formation k(+2) and the bimolecular inhibition constant k(i) for the inhibition of acetylcholinesterase by aminophenol derivatives 3b-d and 4c-e. The conclusions of this study can be summarized as follows for both families: (a) the aromatic moiety played a critical role in the recognition of the active site; (b) in case of the reversible inhibitor, when the ester function took the place of the hydroxyl fragment, there was an important increase in the affinity; and (c) the distance between phenolic hydroxyl and nitrogen was critical because the inhibition is ortho<<meta

Transbilayer diffusion of divalent cations into liposomes mediated by lipidic particles of phosphatidate

Liposomes formed from egg-yolk phosphatidylcholine:egg-yolk phosphatidate (molar ratio 2:1) containing pBR322 DNA and DNase I were induced to form, with divalent cations, bilayer/nonbilayer phase transitions of phosphatidate which allowed cation diffusion into liposomes; then cation diffusion was measured by the activation of the hydrolysis of DNase I on DNA. The formation of phosphatidate transitions on liposomes was demonstrated by freeze-fracture and 31P NMR, and a direct correlation between the formation of phosphatidate transitions and the transbilayer diffusion of cations was found: only Ca2+ and Mn2+, which induce phase transitions, were able to penetrate liposomes and triggered the DNase I activity; in addition, Ca2+ at higher concentrations (10 mM) caused fusion of liposomes, whereas Mn2+ did not, suggesting that transitions induced by Mn2+ participated only in the diffusion of this ion; furthermore, Mg2+ neither formed phase transitions nor triggered the enzymatic activity. The liposomes studied represent more dynamic structures that can form phosphatidate structures involved in both (1) the interchange of divalent cations with the surroundings, thereby modulating encapsulated enzymes, and (2) the fusion of lipid vesicles probably implicated in the enrichment of liposomal content in the early Precambian Earth.

X-ray analysis and structural characterization of 2-phenyl-6-aza-1,3- dioxa-2-borabenzocyclononenones

Nine new monomeric boronates of the type 2-phenyl-6-aza-1,3-dioxa-2-borabenzocyclononen-4-ones (3a � /3i) were prepared from N -(2-hydroxybenzyl)-a-aminoacids 1a � /1i and phenylboronic acid 2 using 20:1 benzene � /DMSO mixtures. The compounds were characterized by 1 H-, 13 C-, 11 B-, 15 N- and 2D-NMR (HETCOR, NOESY and COLOC) experiments, FT infrared, mass spectra and elemental analysis. Suitable monocrystals of cis -2-phenyl-6-aza-1,3-dioxa-2-borabenzocyclononen-4-one (3a), (2S ,5S ,6R )-2phenyl-6-aza-1,3-dioxa-5-sec butyl-2-borabenzocyclononen-4-one (3e) and 2,5-diphenyl-6-aza-1,3-dioxa-2-borabenzocyclononen-4one (3h) were obtained and their structures are discussed. The X-ray structures, as well as the NMR data established that the configurations at the nitrogen and boron atoms are ‘R ’ and ‘S ’, respectively and the transannular fusion is cis . A semi-empirical (SAM1) study allowed calculation of the energy for all possible stereoisomers, showing that the stabilization increases as the THC (TetraHedral Character of the boron atom) increases and also as the N 0/B bond distance decreases, in agreement with the experimental results. # 2002 Elsevier Science B.V. All rights reserved.

X-ray crystallographic study of neutral boron chelates with ?-diketones and tropolone

A series of six new boron β-diketonates and tropolonates has been synthesized, each compound being crystallized and characterized by spectroscopic methods as well as by X-ray crystallography. A comparative study of the NMR and X-ray data with similar structures from the literature permitted us to develop a detailed evaluation of the bonding in these chelates that lead to several interesting correlations. The present compounds have important physical properties that justify this study.