Iron-57 NMR and Structural Study of [Fe(η⁵‑Cp)(SnPh₃)(CO)(PR₃)] (PR₃ = Phosphine, Phosphite). Separation of Steric and Electronic σ and π Effects

The complexes [Fe­(Cp)­(SnPh₃)­(CO)­(PR₃)] (PR₃ = PMe₃ (<b>1</b>), PⁿBu₃ (<b>2</b>), PCy₃ (<b>3</b>), PMe₂Ph (<b>4</b>), PMePh₂ (<b>5</b>), P­(CH₂Ph)₃ (<b>6</b>), PPh₃ (<b>7</b>), P­(4-MeC₆H₄)₃ (<b>8</b>), P­(4-MeOC₆H₄)₃ (<b>9</b>), P­(4-FC₆H₄)₃ (<b>10</b>), P­(4-CF₃C₆H₄)₃ (<b>11</b>), P­(NMe₂)₃ (<b>12</b>), P­(OMe)₃ (<b>13</b>), P­(OPh)₃ (<b>14</b>)), which have been characterized by X-ray crystallography (except for <b>1</b> and <b>4</b>), infrared spectroscopy (carbonyl stretching frequency, ν_CO), and NMR spectroscopy (¹³C, ³¹P, ⁵⁷Fe, ¹¹⁹Sn) offer some insight into the response of the iron nucleus to changes in the electronic and steric properties of the PR₃ ligand. A fairly good correlation is found between the ⁵⁷Fe chemical shift and the Tolman cone angle θ for PR₃ and a rather poorer correlation between δ­(⁵⁷Fe) and ν_CO. However, for the subseries of complexes <b>7</b>–<b>11</b> having PR₃ = P­(4-XC₆H₄)₃ (X = H, Me, MeO, F, CF₃), the correlation between δ­(⁵⁷Fe) and ν_CO is very good. Since the steric properties of these ligands, from the point of view of the metal, are identical (θ = 145°), this provides a means of separating the steric and electronic contributions of PR₃ to δ­(⁵⁷Fe). The electronic contribution of PR₃ to δ­(⁵⁷Fe) can be further separated into σ and π components by making use of the finding that the π component of the Fe–P bond has a negligible influence on δ­(⁵⁷Fe), unlike its influence on ν_CO. The ligands PMe_3, PⁿBu₃, PCy₃, PMe₂Ph, PMePh₂, and P­(NMe₂)₃ are found to be “pure” σ donors, P­(OMe)₃ and P­(OPh)₃ are found to be π acceptors of differing strength, and P­(4-XC₆H₄)₃ is found to show weak but clearly distinguishable π acceptor properties

Synthesis, Conformational Analysis and Evaluation of the 2-aryl-4-(4-bromo-2-hydroxyphenyl)benzo[1,5]thiazepines as Potential &alpha;-Glucosidase and/or &alpha;-Amylase Inhibitors

The ambident electrophilic character of the 5-bromo-2-hydroxychalcones and the binucleophilic nature of 2-aminothiophenol were exploited to construct the 2-aryl-4-(4-bromo-2-hydroxyphenyl)benzo[1,5]thiazepines. The structures and conformation of these 2-aryl-4-(4-bromo-2-hydroxyphenyl)benzo[1,5]thiazepines were established with the use of spectroscopic techniques complemented with a single crystal X-ray diffraction method. Both 1H-NMR and IR spectroscopic techniques confirmed participation of the hydroxyl group in the intramolecular hydrogen-bonding interaction with a nitrogen atom. SC-XRD confirmed the presence of a six-membered intramolecularly hydrogen-bonded pseudo-aromatic ring, which was corroborated by the DFT method on 2b as a representative example in the gas phase. Compounds 2a (Ar = -C6H5), 2c (Ar = -C6H4(4-Cl)) and 2f (Ar = -C6H4(4-CH(CH3)2) exhibited increased inhibitory activity against &alpha;-glucosidase compared to acarbose (IC50 = 7.56 &plusmn; 0.42 &micro;M), with IC50 values of 6.70 &plusmn; 0.15 &micro;M, 2.69 &plusmn; 0.27 &micro;M and 6.54 &plusmn; 0.11 &micro;M, respectively. Compound 2f, which exhibited increased activity against &alpha;-glucosidase, also exhibited a significant inhibitory effect against &alpha;-amylase (IC50 = 9.71 &plusmn; 0.50 &micro;M). The results of some computational approaches on aspects such as noncovalent interactions, calculated binding energies for &alpha;-glucosidase and &alpha;-amylase, ADME (absorption, distribution, metabolism and excretion) and bioavailability properties, gastrointestinal absorption and blood&ndash;brain barrier permeability are also presented