Abstract: (1E,3Z)-1-Aryl-4-methanesulfonyl-2-nitro-1,3-butadienes (8), derived from the initial ring-opening of 3-nitrothiophene (5), have been found to undergo a facile base-induced cyclization leading to thiopyran S,S-dioxides (9), thus furnishing a further example of effective ring-enlargement from 5- to 6-membered sulfur heterocycles. Compounds 9 are obtained as single racemic mixtures in satisfactory yields; they still contain a nitrovinylic moiety, which can be exploited for further modifications targeted to new derivatives endowed with either synthetic or pharmacological potentialities e.g., in the field of L-type Ca2+-channel blockers.
Abstract: Hybrid QM(CASPT2//CASSCF/6âËâ31G*)/MM(Amber) computations have been used to map the photoisomerization path of the retinal chromophore in Rhodopsin and explore the reasons behind the photoactivity efficiency and spectral control in the visual pigments. It is shown that while the electrostatic environment plays a central role in properly tuning the optical properties of the chromophore, it is also critical in biasing the ultrafast photochemical event: it controls the slope of the photoisomerization channel as well as the accessibility of the S1/S0 crossing space triggering the ultrafast decay. The roles of the E113 counterion, the E181 residue, and the other amino acids of the protein pocket are explicitly analyzed: it appears that counterion quenching by the protein environment plays a key role in setting up the chromophoreââ¬â¢s optical properties and its photochemical efficiency. A unified scenario is presented that discloses the relationship between spectroscopic and mechanistic properties in rhodopsins and allows us to draw a solid mechanism for spectral tuning in color vision pigments: a tunable counterion shielding appears as the elective mechanism for Lââ âM spectral modulation, while a retinal conformational control must dictate S absorption. Finally, it is suggested that this model may contribute to shed new light into mutations-related vision deficiencies that opens innovative perspectives for experimental biomolecular investigations in this field.
Abstract: The unusual behaviour of alpha-bromo vinylketenes in the cycloaddition reactions with imines is described. This class of vinylketenes behaves as dienophiles in [2+2] reactions, but also displays an unusual diene reactivity in [4+2] reactions. Interestingly, the reactivity of alpha-bromo vinylketenes can be modulated via a fine tuning of the substituents. For instance, a methyl group in the beta-position completely inhibits the [2+2] reaction and the [4+2] pathway is almost exclusively followed. A more hindered ketimine (instead of a simple imine) is enough to activate again the [2+2] mechanism. We have carried out a DFT theoretical investigation to rationalise these experimental observations. We have considered two pathways for the [2+2] reaction involving imine, that is, the endo and exo pathways. The former is favoured in the case of alpha-bromo vinylketenes, while the latter is preferred for non-substituted vinylketenes. Since the [4+2] cycloaddition becomes possible only when the s-Z-conformation of vinylketene is significantly populated, the presence of bromine substituents in this substrate is crucial in determining the [2+2] or [4+2] mechanisms. For unsubstituted vinylketenes, the barrier connecting the s-E- to the s-Z-conformation is too high to be easily overcome. Thus, the s-Z-structure has a low population and the [2+2] mechanism is favoured. In the case of alpha-bromo vinylketenes (especially the beta-methyl-substituted ones), this barrier can be surmounted and the [4+2] mechanism becomes available.
Abstract: Abstract Some aspects of the catalytic mechanism of HCA have been investigated. Either a zinc-bound water or a zinc-bound hydroxide has been considered as a nucleophile attacking CO 2. No reaction path exists in the former case, while a transition state for the nucleophilic attack has been located in the latter (barrier of 7.6 kcal molâ1). This activation energy is determined by the breaking of the hydrogen-bond network that shields the zinc-bound hydroxide when the CO 2 molecule approaches the reaction center. No ambiguity exists about the mechanism for the internal rearrangement of the zincâbicarbonate complex. The rotation pathway (Lindskog mechanism) proposed by many authors is too energy demanding since it causes the breaking of the hydrogen-bond network around the bicarbonate. The only possible rearrangement mechanism is a proton transfer (Lipscomb) that occurs in two steps (each step corresponding to a double proton transfer) and involves the Thr199 residue as a proton shuttle.
Abstract: Abstract In the last decade combined quantum mechanic/ molecular mechanic (QM/MM) methods have been applied to a large variety of chemical problems. This paper describes a new QM/MM implementation that acts as a flexible computational environment. Specifically, geometry optimizations, frequency calculations and molecular dynamics can be performed on the investigated system that can be split up to three different layers corresponding to different levels of accuracy. Here we report, together with a detailed description of the method and its implementation, some test examples on very different chemical problems, which span the wide and diversified area of chemistry (from ground to excited states topics) and show the flexibility, general applicability and accuracy of the presented hybrid approach. Biochemical, photobiological and supra/super-molecular applications are presented for this purpose: (a) the optimized geometry of a rotaxane is compared with its X-ray structure; (b) the computed absorption spectra of the green fluorescent protein and rhodopsin chromophores in different environments (namely solvent and protein) are compared to the corresponding experimental values and the role of the counter ion and ion pairs in tuning the geometrical and optical properties of charged organic chromophores in polar solvents is explored and discussed; (c) problems and open questions related to the model set-up of a protein are investigated in the framework of the TcPRAC-protein racemase; (d) similarities and differences between the QM and QM/MM reaction path for the HIV1-protease enzymatic mechanism are shown and discussed; (e) the delicate anomeric equilibrium of α- and β â D-glucopyranose in water is investigated via QM/MM optimizations and molecular dynamics to show the reliability of the actual implementation in the simulation of solvation effects and delicate balances. Finally, it will be shown that the current implementation (called COBRAMM: Computations at Bologna Relating Ab-initio and Molecular Mechanics Methods) is more than a simple QM/MM method, but a more general hybrid approach with a modular structure that is able to integrate some specialized programs, which may increase the flexibility/efficiency of QM, MM and QM/MM calculations.
Abstract: The Mukaiyama-Michael-type addition of various silyl ketene acetals or silyl enol ethers on some 1,2-diaza-1,3-butadienes proceeds at room temperature in the presence of catalytic amounts of Lewis acid affording by heterocyclization 1-aminopyrrol-2-ones and 1-aminopyrroles, respectively. 1-Aminoindoles have been also obtained by the same addition of 2-(trimethylsilyloxy)-1,3-cyclohexadiene on some 1,2-diaza-1,3-butadienes and subsequent aromatization. Mechanistic investigations indicate the coordination by Lewis acid of the enolsilyl derivative and its 1,4-addition on the azo-ene system of 1,2-diaza-1,3-butadienes. The migration of the silyl group from a hydrazonic to an amidic nitrogen, its acidic cleavage and the final internal heterocyclization give the final products. Based on NMR studies and ab initio calculations, a plausible explanation for the migration of the silyl protecting group is presented.
