RESUMO

The importance of electrostatic nonconventional hydrogen bonds (NCHBs) to the pseudo-anomeric effect of 4-substituted methoxycyclohexanes is evaluated using theory [natural bond orbital (NBO)] to deconvolute electrostatic from other contributing effects. There is an interesting interplay between σCH → σCX* hyperconjugation and the electropositive charge on 3,5-axial hydrogens (Hax). In essence, better σCX* (or πCO*) acceptors increase the charge on 3,5-CHax, which in turn strengthens Cδ+Hax···Î´-OMe NCHB interactions.

RESUMO

In this theory study we demonstrate the dominance of non-classical 1,3-diaxial CHaxOC hydrogen bonds (NCHBs) dictating a 'pseudo' anomeric effect in selectively fluorinated methoxycyclohexanes and also influencing the axial preference in the classical anomeric exhibitor 2-methoxytetrahydropyran, a phenomenon which is most often described as a consequence of hyperconjugation. Analogues of methoxycyclohexane where ring CH2's are replaced by CF2 can switch to an axial preference and theory methods (NBO, QTAIM, NCI) indicate the dominance of 1,3-CHaxOMe interactions over hyperconjugation. For 2-methoxytetrahydropyran, it is revealed that the global contribution to the anomeric effect is from electrostatic interactions including NCHBs, not hyperconjugation, although hyperconjugation (nO→σ*CO or nO→σ*CC) remains the main contributor to the exo-anomeric phenomenon. When two and three ether oxygens are introduced into the ring, then both the NCHB interactions and hyperconjugative contributions become weaker, not stronger as might have been anticipated, and the equatorial anomers progressively dominate.

RESUMO

We report counter-intuitive axial preferences in non-stereochemically biased, selectively fluorinated methoxycyclohexanes. These pseudo-anomeric effects are apparent when electronegative CF2 groups are placed at the C-2, C-4 and C-6 positions of the cyclohexane ring to render the C-3/5 axial hydrogen atoms electropositive. The electrostatic interaction between these axial hydrogen atoms and the -OMe oxygen is stabilising. The effect is explored using high-level ab initio and DFT calculations in the framework of NBO, QTAIM and NCI analysis across a range of derivatives, and experimentally (19 F{1 H}-NMR at -80 °C) for some illustrative examples. The effect is significant in energy terms for a weak interaction, and illustrates a new stereoelectronic aspect attributed to selective fluorine substitution in organic chemistry.

RESUMO

Hyperconjugative, steric, and electrostatic effects were evaluated as possible sources of the helicity in linear perfluorinated alkanes through analysis of natural bond orbitals and classical electrostatics. Contrary to previous rationalizations, which indicate dominating steric or electrostatic effects, this analysis indicates that hyperconjugative stabilization through σCC →σ*CF interactions are the underlying driving force for the origin of the observed helicity in perfluoroalkanes.

RESUMO

The fluorinase is an enzyme that catalyses the combination of S-adenosyl-L-methionine (SAM) and a fluoride ion to generate 5'-fluorodeoxy adenosine (FDA) and L-methionine through a nucleophilic substitution reaction with a fluoride ion as the nucleophile. It is the only native fluorination enzyme that has been characterised. The fluorinase was isolated in 2002 from Streptomyces cattleya, and, to date, this has been the only source of the fluorinase enzyme. Herein, we report three new fluorinase isolates that have been identified by genome mining. The novel fluorinases from Streptomyces sp. MA37, Nocardia brasiliensis, and an Actinoplanes sp. have high homology (80-87 % identity) to the original S. cattleya enzyme. They all possess a characteristic 21-residue loop. The three newly identified genes were overexpressed in E. coli and shown to be fluorination enzymes. An X-ray crystallographic study of the Streptomyces sp. MA37 enzyme demonstrated that it is almost identical in structure to the original fluorinase. Culturing of the Streptomyces sp. MA37 strain demonstrated that it not only also elaborates the fluorometabolites, fluoroacetate and 4-fluorothreonine, similar to S. cattleya, but this strain also produces a range of unidentified fluorometabolites. These are the first new fluorinases to be reported since the first isolate, over a decade ago, and their identification extends the range of fluorination genes available for fluorination biotechnology.

Assuntos

Proteínas de Bactérias/metabolismo , Genoma Bacteriano , Micromonosporaceae/genética , Nocardia/genética , Oxirredutases/metabolismo , Streptomyces/genética , Proteínas de Bactérias/genética , Sítios de Ligação , Cristalografia por Raios X , Escherichia coli/metabolismo , Fluoretação , Fluoretos/química , Fluoretos/metabolismo , Cinética , Micromonosporaceae/enzimologia , Família Multigênica , Nocardia/enzimologia , Oxirredutases/genética , Estrutura Terciária de Proteína , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , S-Adenosilmetionina/química , S-Adenosilmetionina/metabolismo , Streptomyces/enzimologia

RESUMO

The conformational preference of the widely utilized anesthetic fluoromethyl-1,1,1,3,3,3-hexafluoro-2-propyl ether (sevoflurane) has been investigated computationally and by NMR spectroscopy. Three conformational minima were located at the B3LYP/aug-cc-pVDZ level, but one is significantly more stable (by ca. 4 kcal/mol) than the other two. This is the case both for gas phase calculations and for solution NMR data. Although the main conformer is stabilized by electron delocalization (n(O) → σ*(C-F)), this type of hyperconjugation was not found to be the main driver for the conformer stabilization in the gas phase and, consequently, for the apparent anomeric effect in sevoflurane. Instead, more classical steric and electrostatic interactions appear to be responsible for the conformational energies. Also the (1)J(CF) coupling constants do not appear to be dominated by hyperconjugation; again, dipolar interactions are invoked instead.