Silyliumylidene Ion Stabilized by Two σ-Donating Ni(0)- and Pd(0)-Fragments.

A silyliumylidene ion 2 stabilized by two σ-donating Ni(0)- and Pd(0)-fragments was successfully synthesized. Due to the σ-donation of M→Si interactions, 2 presents a pyramidalized cationic silicon center with a localized lone pair. The additional coordination of basic Pd(0) fragment to the mono-Ni(0)-stabilized silyliumylidene 1 results in a higher HOMO level and an unchanged HOMO-LUMO gap and thus, 2 remains highly reactive. Interestingly, the coordination mode at the Si center is closely related to the nature of M-ligands. Indeed, the donor/donor-stabilized silyliumylidene ion 2 has been transformed into a donor/acceptor-stabilized ion 13, featuring a trigonal planar Si center with a vacant orbital, just via a ligand exchange reaction from PCy3/NHC toward PMe3.

Ring-opening polymerization of cyclic oligosiloxanes without producing cyclic oligomers.

A long-standing problem associated with silicone synthesis is contamination of the polymer products with 10 to 15% cyclic oligosiloxanes that results from backbiting reactions at the polymer chain ends. This process, in competition with chain propagation through ring-opening polymerization (ROP) of cyclic monomers, was thought to be unavoidable and routinely leads to a thermodynamically controlled reaction mixture (polymer/cyclic oligosiloxanes = 85/15). Here, we report that simple alcohol coordination to the anionic chain ends prevents the backbiting process and that a well-designed phosphonium cation acts as a self-quenching system in response to loss of coordinating alcohols to stop the reaction before the backbiting process begins. The combination of both effects allows a thermodynamically controlled ROP of the eight-membered siloxane ring D4 without producing undesirable cyclic oligosiloxanes.

Base-Stabilized Cationic Silyne with a π-Accepting Phosphonio Substituent.

A base-stabilized C-phosphonio-Si-amino-silyne 3 was synthesized, using an original method, through a coupling reaction between two Lewis-base-stabilized low-valent species: a silyliumylidene ion 1 and a P,S-bis-ylide 2 [C(0)-complex]. This new isolable cationic silyne 3 displays remarkably high stability at room temperature [t1/2 = 7 days in tetrahydrofuran (THF)] and a unique silyne reactivity thanks to the effect of phosphonio substituent.

Reversible Isomerization Between Silacyclopropyl Cation and Cyclic (Alkyl)(Amino)Silylene.

A phosphine-stabilized silacyclopropyl cation 2 has been synthesized and fully characterized. Of particular interest, 2 reversibly isomerizes into the corresponding seven-membered cyclic (alkyl)(amino)silylene 3 at room temperature via a formal migratory ethylene insertion into the Si-P bond. Although silylene 3 has not been spectroscopically detected, its transient formation has been evidenced by the isolation of the corresponding disilene dimer 5 as well as by trapping reactions.

Labile Base-Stabilized Silyliumylidene Ions. Non-Metallic Species Capable of Activating Multiple Small Molecules.

Several base-stabilized silyliumylidene ions (2 and 3) with different ligands were synthesized. Their behaviour appeared strongly dependent on the nature of ligand. Indeed, in contrast to the poorly reactive silyliumylidene ions 3 c,d stabilized by strongly donating ligands (DMAP, NHC), the silylene- and sulfide-supported one (2-H and 3 a) exhibits higher reactivity toward various small molecules. Furthermore, their capability to successively activate multiple small molecules was clearly demonstrated by processes involving successive reactions with silane/formamide, CO2 and H2 . Moreover, HBPin adduct of 3 a (8-C) catalyzes the hydroboration of pyridine. Of particular interest, silylene-supported silyliumylidene complex 2-H is one of the rare species able to activate two H2 molecules.

Synthesis, Characterization and Reactivity of a σ-Donating Ni0 -Stabilized Silyliumylidene Ion.

The synthesis of a silyliumylidene cation complex 2 stabilized by a Ni0 -based donating ligand is reported. Experimental and theoretical studies demonstrate that the highly electrophilic SiII center is stabilized by a dative Ni→Si σ-interaction and π-donations from the amino- and Ni-moieties. Due to the energetically close frontier orbitals localized on the Si and Ni atoms, complex 2 presents a competitive reactivity at Si and Ni sites.

A Silylene Stabilized by a σ-Donating Nickel(0) Fragment.

A donor-stabilized silylene 4 featuring a Ni0 -based donating ligand was synthesized. Complex 4 exhibits a pyramidalized and nucleophilic SiII center and shows a peculiar behavior due to the cooperative reactivity of Si and Ni centers. Calculations indicate that the orientation of Ni-ligands with respect to the silylene moiety is crucial in determining the role of the Ni-fragment (Lewis acid or Lewis base) towards silylene. Indeed, a simple 90° rotation of the Si-Ni bond, reverses the role of Ni, and transforms a classical silylene→Ni0 complex into an unprecedented Ni0 →silylene complex.

Strained and Reactive Donor/Acceptor-Supported Metallasilanone.

A novel stable donor/acceptor-supported MnI -metallasilanone 3 was synthesized. The intramolecular silanone-MnI interaction induces a highly strained three-membered cyclic structure, leading to an exceptionally high reactivity of 3 as a donor/acceptor complex of silanone. Indeed, metallasilanone 3 readily reacts with various small molecules such as H2 or ethylene gas in mild conditions.

Efficient DNA Condensation Induced by Chiral ß-Amino Acid-Based Cationic Surfactants.

Four cationic chiral amino acid-based surfactants, cis- and trans-1 and cis- and trans-2, have been studied as DNA-condensing agents with enhanced properties and the absence of cell toxicity. The polar head of the surfactant is made of a cyclobutane ß-amino acid in which the amino group is a hydrochloride salt and the carboxyl group is involved in an amide bond, allowing the link with hydrophobic C12 (surfactant 1) or C16 (surfactant 2) chains. The ability of these surfactants to condense DNA was investigated using a dye exclusion assay, gel electrophoresis, and circular dichroism and compared with the well-studied dodecyltrimethylammonium bromide (DTAB) and cetyltrimethylammonium bromide (CTAB). The surfactant with the longest chain length and the trans stereochemistry (trans-2) was found to be the most efficient in condensing the DNA, including CTAB. Surfactant cis-2 was found to be less efficient, probably due to its poorer solubility. The ß-amino acid surfactants with the shorter chain length behaved similarly, such that the cis/trans stereochemistry does not seem to play a role in this case. Interestingly, these were also found to induce DNA condensation for the same concentration as trans-2 and CTAB but showed a lower binding cooperativity. Therefore, a longer alkyl chain only slightly improved the effectiveness of these surfactants. Further, atomic force microscopy revealed that they compact DNA into small complexes of about 55-110 nm in diameter.

Catalytic Effect of Electric Fields on the Kemp Elimination Reactions with Neutral Bases.

The effect of solvent reaction fields and oriented electric fields on the Kemp elimination reaction between methylamine or imidazole and 5-nitrobenzisoxazole has been theoretically studied. The Kemp reaction is the most widely used for the design of new enzymes. Our results, using the SMD continuous model for solvents, are in quite good agreement with the experimental fact that the rate of the analogous reaction with butylamine is one order of magnitude smaller in water than in acetonitrile. In the case of external electric fields, our results show that they can increase or decrease the energy barrier depending on the magnitude and orientation of the field. A duly oriented electric field may have a notable catalytic effect on the reaction. So, external electric fields and reaction fields due to the medium can contribute to the design of new enzymes. Several factors that must be taken into account to increase the catalytic effect are discussed.

Synthesis of a Stable N-Hetero-RhI -Metallacyclic Silanone.

A novel N-hetero-RhI -metallacyclic silanone 2 has been synthesized. The silanone 2, showing an extremely large dimerization energy (ΔG=+86.2 kcal mol-1 ), displays considerable stability and persists in solution up to 60 °C. Above 120 °C, an intramolecular Csp3 -H insertion occurs slowly over a period of two weeks leading to the bicyclic silanol 5. The exceptional stability of 2, related to the unusual electronic and steric effects of RhI -substituent, should allow for a more profound study and understanding of these new species. Furthermore, the metallacyclic silanone 2 presents two reactive centers (Si=O and Rh), which can be involved depending upon the nature of reagents. Of particular interest, the reaction with H2 starts with the hydrogenation of RhI center leading to the corresponding RhIII -dihydride complex 7 and it undergoes a cis/trans-isomerization via a particular mechanism, demonstrating that addition-elimination processes can also happen for silanones just like for their carbon analogues!

Kemp Elimination Reaction Catalyzed by Electric Fields.

The Kemp elimination reaction is the most widely used in the de novo design of new enzymes. The effect of two different kinds of electric fields in the reactions of acetate as a base with benzisoxazole and 5-nitrobenzisoxazole as substrates have been theoretically studied. The effect of the solvent reaction field has been calculated using the SMD continuum model for several solvents; we have shown that solvents inhibit both reactions, the decrease of the reaction rate being larger as far as the dielectric constant is increased. The diminution of the reaction rate is especially remarkable between aprotic organic solvents and protic solvents as water, the electrostatic term of the hydrogen bonds being the main factor for the large inhibitory effect of water. The presence of an external electric field oriented in the direction of the charge transfer (z axis) increases it and, so, the reaction rate. In the reaction of the nitro compound, if the electric field is oriented in an orthogonal direction (x axis) the charge transfer to the NO2 group is favored and there is a subsequent increase of the reaction rate. However, this increase is smaller than the one produced by the field in the z axis. It is worthwhile mentioning that one of the main effects of external electric fields of intermediate intensity is the reorientation of the reactants. Finally, the implications of our results in the de novo design of enzymes are discussed.

Unraveling the Modulation of the Activity in Drugs Based on Methylated Phenanthroline When Intercalating between DNA Base Pairs.

Phenanthroline derivatives intercalate between base pairs of DNA and produce cytotoxic effects against tumoral cells. Nevertheless, modulation of their efficiency by substitution remains unclear in bibliography. In this work, the effects of methylation of phenanthroline, in number and position, when it intercalates between guanine-cytosine base pairs (GC/CG), were studied with PM6-DH2 and DFT-D methods including dispersion corrections. An analysis of the geometries, electronic structure, and energetics in the interaction was carried out for the studied systems. Our results were compared to experimental works to gain insight on the relation structure-interaction for the intercalated system with cytotoxicity. The trends are explained including not only intrinsic contributions to energy, ΔEPauli, ΔEdisp, ΔEorb, and ΔEelstat, but also the solvation energy, ΔESolv. A subtle balance between the number of stabilizing weak interactions (CH/π, CH/n, etc.) and steric hindrance seems to be related to the efficiency of such drugs.

A Stable N-Hetero-Rh-Metallacyclic Silylene.

A cyclic (amino)metal-substituted dicoordinated silylene derivative has been synthesized and fully characterized. Of particular interest is that the N-hetero-RhI -metallacyclic silylene exhibits a distorted tetrahedral geometry around the rhodium atom and a considerably shortened Si-Rh bond (2.138 Å) compared to classical Si-Rh single bonds (ca. 2.30-2.35 Å). A theoretical investigation reveals that the geometrical deviation around the rhodium center from the classical square-planar to a tetrahedral geometry increases the π-donating and σ-accepting character of the rhodium atom, thereby efficiently stabilizing the silylene moiety.

Synthesis and Gelling Abilities of Polyfunctional Cyclohexane-1,2-dicarboxylic Acid Bisamides: Influence of the Hydroxyl Groups.

New enantiomerically pure C16-alkyl diamides derived from trihydroxy cyclohexane-1,2-dicarboxylic acid have been synthesized from (-)-shikimic acid. The hydroxyl groups in these compounds are free or, alternatively, they present full or partial protection. Their gelling abilities towards several solvents have been tested and rationalized by means of the combined use of Hansen solubility parameters, scanning electron microscopy (SEM), and circular dichroism (CD), as well as computational calculations. All the results allowed us to account for the capability of each type of organogelator to interact with different solvents and for the main mode of aggregation. Thus, compounds with fully protected hydroxyl groups are good organogelators for methanol and ethanol. In contrast, a related compound bearing three free hydroxyl groups is insoluble in water and polar solvents including alcohols but it is able to gelate some low-polarity solvents. This last behavior can be justified by strong hydrogen bonding between molecules of organogelator, which competes advantageously with polar solvent interactions. As an intermediate case, an organogelator with two free hydroxyl groups presents an ambivalent ability to gelate both apolar and polar solvents by means of two aggregation patterns. These involve hydrogen bonding interactions of the unprotected hydroxyl groups in apolar solvents and intermolecular interactions between amide groups in polar ones.

Cyclobutane Scaffold in Bolaamphiphiles: Effect of Diastereoisomerism and Regiochemistry on Their Surface Activity Aggregate Structure.

Cationic bolaamphiphiles have been synthesized starting from meso cis- or chiral trans-1,2-difunctionalized cyclobutane derivatives. They include cis/trans pairs of diastereoisomers, of N- or C-centered bisamides. The goal of this work was to investigate the influence of stereochemistry and regiochemistry on their abilities as surfactants and self-assembly. Very large differences in surface coverage (2-fold), critical micellar concentration (cmc, up to 2 orders of magnitude), and aggregate structure (from lamellae to fibers) for the four molecules are remarkable due to regio- and stereochemistry differences. Computational calculations were carried out to rationalize the experimental findings and a new methodology has been developed to calculate the structure of these bolaamphiphiles at the surface. Although the four surfactants adopt a wicket-like conformation, for N-centered trans, the distance between polar heads is much larger than that for the other three molecules, as suggested by calculations. We have shown that the interplay between the regiochemistry and stereoisomerism, enhanced by rigidity of the cyclobutane ring, affects different physicochemical properties quite differently. That is, the cmc value is mainly governed by stereochemistry, with regiochemistry only modulating this value. On the other hand, regiochemistry definitely governs the morphology of the supramolecular aggregates (i.e., long fibers versus plates or spherical assemblies), with stereochemistry finely modulating their structural parameters. All these results must help in the rational design of new bolaamphiphiles with predictable properties and useful potential applications.

Phosphoryl-Transfer Reaction in RNA under Alkaline Conditions.

The phosphoryl-transfer reaction in RNA under alkaline conditions by exploring the influence of several solvents theoretically was studied. The calculations were carried out by using the M06-2X functional and the solvents were taken as a continuum by using the solvent model density (SMD) method. The main findings show that the O2'-P-O5' angle in the reactants, the free activation energies, and the reaction mechanism are clearly dependent on the dielectric constant of the environment, thus showing that the electrostatic term is the determining factor for this chemical system with two negative charges. Our study seems to indicate that water, the solvent with the greatest dielectric constant, would be the solvent that increases the reaction rate the most. As this outcome was not the case in enzymatic catalysis, one has to conclude that, in the case of proteins as well as for ribozymes, the enzymatic catalysis is not mainly due to the solvent reaction field, but to local electrical fields as a result of enzyme preorganization.

Phosphine/Sulfoxide-Supported Carbon(0) Complex.

A new carbon(0) complex 2 with two different L ligands, a phosphine and a sulfoxide, was synthesized and fully characterized. This new type of carbone exhibits excellent coordination ability, in contrast to the related phosphine/sulfide-supported carbon(0) complexes. Several organometallic complexes were isolated and, of special interest, the νav (CO) value of RhI -dicarbonyl complex indicates that 2 has a donor capability superior to classical NHCs.

Reversible CO2 Addition to a Si=O Bond and Synthesis of a Persistent SiO2 -CO2 Cycloadduct Stabilized by a Lewis Donor-Acceptor Ligand.

The donor-stabilized sila-ß-lactone 1 reacts with CO2 via a remarkable reversible [2+2]-cycloaddition reaction to form the spiro-cyclic silicon carbonate derivative 2. Furthermore, photolysis of 2 under pressure of CO2 affords the first persistent SiO2 -CO2 cycloadduct 3, presenting a Si2 O4 -like structure, which is stabilized by a Lewis donor-acceptor type ligand. As predicted by theoretical calculations, in marked contrast to the thermodynamically stable SiO2 dimer, the SiO2 -CO2 mixed cycloadduct 3 is labile and readily releases CO2 .

Stereoselectivity of Proline/Cyclobutane Amino Acid-Containing Peptide Organocatalysts for Asymmetric Aldol Additions: A Rationale.

Several α,ß,α- or α,γ,α-tripeptides, consisting of a central cyclobutane ß- or γ-amino acid being flanked by two d- or l-proline residues, have been synthesized and tested as organocatalysts in asymmetric aldol additions. High yields and enantioselectivities have been achieved with α,γ,α-tripeptides, being superior to peptides containing a cyclobutane ß-amino acid residue. This is probably due to their high rigidity, which hinders some of the peptide catalysts to adopt the proper active conformation. This reasoning correlates with the major conformation of the peptides in the ground state, as suggested by 1H NMR and computational calculations. The configuration of the aldol products is controlled by the proline chirality, and consequently, the R/S configuration of aldol products can be tuned by the use of either commercially available d- or l-proline. The enantioselectivity in the aldol reactions is reversed if the reactions are carried out in the presence of water or other protic solvents such as methanol. Spectroscopic and theoretical investigations revealed that this effect is not the consequence of conformational changes in the catalyst but rather caused by the participation of a water molecule in the rate determining transition state, in such a way that the preferential nucleophilic attack is oriented to the opposite enantiotopic aldehyde face.