We have used experimental studies and DFT calculations to investigate the IrIII‐catalyzed isomerization of allylic alcohols into carbonyl compounds, and the regiospecific isomerization–chlorination ...of allylic alcohols into α‐chlorinated carbonyl compounds. The mechanism involves a hydride elimination followed by a migratory insertion step that may take place at Cβ but also at Cα with a small energy‐barrier difference of 1.8 kcal mol−1. After a protonation step, calculations show that the final tautomerization can take place both at the Ir center and outside the catalytic cycle. For the isomerization–chlorination reaction, calculations show that the chlorination step takes place outside the cycle with an energy barrier much lower than that for the tautomerization to yield the saturated ketone. All the energies in the proposed mechanism are plausible, and the cycle accounts for the experimental observations.
Experimental and DFT calculations have been used to understand the mechanism of the IrIII‐catalyzed isomerization of allylic alcohols into carbonyl compounds, and the regiospecific isomerization–chlorination of allylic alcohols into α‐chlorinated carbonyl compounds. The results presented, point to the importance of using an experimental–computational approach to comprehend the mechanisms of complex reactions (see scheme).
The first method to access unsymmetrical aliphatic acyloins is presented. The method relies on a fast 1,3‐hydride shift mediated by an IrIII complex in allylic alcohols followed by oxidation with ...TEMPO+. The direct conversion of allylic alcohols into acyloins is achieved in a one‐pot procedure. Further functionalization of the Cα′ of the α‐amino‐oxylated ketone products gives access to highly functionalized unsymmetrical aliphatic ketones, which further highlights the utility of this transformation.
Selective oxidation: A selective method to synthesize unsymmetrical acyloins as single constitutional isomers is presented. From allylic alcohols, a fast iridium‐catalyzed 1,3‐hydride followed by an oxidation affords α‐hydroxy carbonyls with outstanding selectivity.
An efficient method for the synthesis of α‐iodoketones from allylic alcohols and elemental iodine is reported. We show in this paper that the isomerization of allylic alcohols catalyzed by ...iridium(III) complexes can be combined with an aerobic oxidative iodination protocol, resulting in a straightforward method for the synthesis of a wide range of α‐iodoketones as single constitutional isomers and in high yields under mild reaction conditions.
Chemotherapy, the mainstay treatment for metastatic cancer, presents serious side effects due to off-target exposure. In addition to the negative impact on patients' quality of life, side effects ...limit the dose that can be administered and thus the efficacy of the drug. Encapsulation of chemotherapeutic drugs in nanocarriers is a promising strategy to mitigate these issues. However, avoiding premature drug release from the nanocarriers and selectively targeting the tumour remains a challenge.
In this study, we present a pioneering method for drug integration into nanoparticles known as mesoporous organosilica drugs (MODs), a distinctive variant of periodic mesoporous organosilica nanoparticles (PMOs) in which the drug is an inherent component of the silica nanoparticle structure. This groundbreaking approach involves the chemical modification of drugs to produce bis-organosilane prodrugs, which act as silica precursors for MOD synthesis. Mitoxantrone (MTO), a drug used to treat metastatic breast cancer, was selected for the development of MTO@MOD nanomedicines, which demonstrated a significant reduction in breast cancer cell viability. Several MODs with different amounts of MTO were synthesised and found to be efficient nanoplatforms for the sustained delivery of MTO after biodegradation. In addition, Fe
O
NPs were incorporated into the MODs to generate magnetic MODs to actively target the tumour and further enhance drug efficacy. Importantly, magnetic MTO@MODs underwent a Fenton reaction, which increased cancer cell death twofold compared to non-magnetic MODs.
A new PMO-based material, MOD nanomedicines, was synthesised using the chemotherapeutic drug MTO as a silica precursor. MTO@MOD nanomedicines demonstrated their efficacy in significantly reducing the viability of breast cancer cells. In addition, we incorporated Fe
O
into MODs to generate magnetic MODs for active tumour targeting and enhanced drug efficacy by ROS generation. These findings pave the way for the designing of silica-based multitherapeutic nanomedicines for cancer treatment with improved drug delivery, reduced side effects and enhanced efficacy.
We have used experimental studies and DFT calculations to investigate the Ir
-catalyzed isomerization of allylic alcohols into carbonyl compounds, and the regiospecific isomerization-chlorination of ...allylic alcohols into α-chlorinated carbonyl compounds. The mechanism involves a hydride elimination followed by a migratory insertion step that may take place at Cβ but also at Cα with a small energy-barrier difference of 1.8 kcal mol
. After a protonation step, calculations show that the final tautomerization can take place both at the Ir center and outside the catalytic cycle. For the isomerization-chlorination reaction, calculations show that the chlorination step takes place outside the cycle with an energy barrier much lower than that for the tautomerization to yield the saturated ketone. All the energies in the proposed mechanism are plausible, and the cycle accounts for the experimental observations.
Dental caries is the major biofilm-mediated oral disease in the world. The main treatment to restore caries lesions consists of the use of adhesive resin composites due to their good properties. ...However, the progressive degradation of the adhesive in the medium term makes possible the proliferation of cariogenic bacteria allowing secondary caries to emerge. In this study, a dental adhesive incorporating a drug delivery system based on L-arginine-containing mesoporous silica nanoparticles (MSNs) was used to release this essential amino acid as a source of basicity to neutralize the harmful acidic conditions that mediate the development of dental secondary caries. The in vitro and bacterial culture experiments proved that L-arginine was released in a sustained way from MSNs and diffused out from the dental adhesive, effectively contributing to the reduction of the bacterial strains Streptococcus mutans and Lactobacillus casei. Furthermore, the mechanical and bonding properties of the dental adhesive did not change significantly after the incorporation of L-arginine-containing MSNs. These results are yielding glimmers of promise for the cost-effective prevention of secondary caries.
A mild base-catalyzed strategy for the isomerization of allylic alcohols and allylic ethers has been developed. Experimental and computational investigations indicate that transition metal catalysts ...are not required when basic additives are present. As in the case of using transition metals under basic conditions, the isomerization catalyzed solely by base also follows a stereospecific pathway. The reaction is initiated by a rate-limiting deprotonation. Formation of an intimate ion pair between an allylic anion and the conjugate acid of the base results in efficient transfer of chirality. Through this mechanism, stereochemical information contained in the allylic alcohols is transferred to the ketone products. The stereospecific isomerization is also applicable for the first time to allylic ethers, yielding synthetically valuable enantioenriched (up to 97% ee) enol ethers.
The selective synthesis of α-functionalized ketones with two similar enolizable positions can be accomplished using allylic alcohols and iridium(III) catalysts. A formal 1,3-hydrogen shift on allylic ...alcohols generates catalytic iridium-enolates in a stereospecific manner, which are able to react with electrophiles to yield α-functionalized ketones as single constitutional isomers. However, the employment of nucleophiles to react with the nucleophilic catalytic enolates in this chemistry is still unknown. Herein, we report an umpolung strategy for the selective synthesis of α-alkoxy carbonyl compounds by the reaction of iridium enolates and alcohols promoted by an iodine(III) reagent. Moreover, the protocol also works in an intramolecular fashion to synthesize 3(2H)-furanones from γ-keto allylic alcohols. Experimental and computational investigations have been carried out, and mechanisms are proposed for both the inter- and intramolecular reactions, explaining the key role of the iodine(III) reagent in this umpolung approach.
Mesoporous silica nanomaterials have emerged as promising vehicles in controlled drug delivery systems due to their ability to selectively transport, protect, and release pharmaceuticals in a ...controlled and sustained manner. One drawback of these drug delivery systems is their preparation procedure that usually requires several steps including the removal of the structure-directing agent (surfactant) and the later loading of the drug into the porous structure. Herein, we describe the preparation of mesoporous silica nanoparticles, as drug delivery systems from structure-directing agents based on the kidney-protector drug cilastatin in a simple, fast, and one-step process. The concept of drug-structure-directing agent (DSDA) allows the use of lipidic derivatives of cilastatin to direct the successful formation of mesoporous silica nanoparticles (MSNs). The inherent pharmacological activity of the surfactant DSDA cilastatin-based template permits that the MSNs can be directly employed as drug delivery nanocarriers, without the need of extra steps. MSNs thus synthesized have shown good sphericity and remarkable textural properties. The size of the nanoparticles can be adjusted by simply selecting the stirring speed, time, and aging temperature during the synthesis procedure. Moreover, the release experiments performed on these materials afforded a slow and sustained drug release over several days, which illustrates the MSNs potential utility as drug delivery system for the cilastatin cargo kidney protector. While most nanotechnology strategies focused on combating the different illnesses this methodology emphasizes on reducing the kidney toxicity associated to cancer chemotherapy.
A regioselective protocol for the synthesis of substituted allylic chlorides, bromides, and fluorides has been established. Remarkably, the method can be applied to the enantioselective synthesis of ...challenging chiral allylic chlorides. When the allylic halides are treated with the base triazabicyclodecene as the catalyst, a 1,3-proton shift takes place, giving the corresponding vinyl halides in excellent yields with excellent
:
ratios. Furthermore, the 1,3-proton shift takes place with an outstanding level of chirality transfer from chiral allylic alcohols (≤98%) to give chiral trifluoromethylated vinyl chlorides.
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