Jih Ru Hwu

The reagent Ca@SiO₂ was obtained by impregnation of silica gel with calcium metal. The presence of Ca@SiO₂ allowed aldehydes to condense with ketones in 2-MeTHF, which resulted in α,β-unsaturated cyclohexenones in 73–90% yields through a radical domino process. Furthermore, Ca@SiO₂ was used to induce a Darzens reaction for the efficient production of α-keto trans-epoxides from benzaldehydes and α-bromo ketones. Being a free-flowing powder, Ca@SiO₂ was easy to handle and facilitated chemoselectivity among many functional groups.

Single-walled carbon nanotubes (SWCNTs) are grafted with multiple phenoxy-triazole-(ethylene glycol) ligands, whose terminals are uniformly functionalized with DNA-binding moieties. Each binder contains one to three binding sites for imidazolidin-2-one, hydantoin, or urazole. Entwinement of these "artificial strands" with ss- and dsDNAs forms pseudoduplex or pseudotriplex DNA structures, respectively. The hybridization preference between the functionalized SWCNTs (i.e., f-SWCNTs 1a-c) and ssDNA is investigated using homo-oligomers ss-dA₂₅, ss-dT₂₅, and ss-dC₂₅. Results show that ss-dA₂₅ bound strongly to f-SWCNT 1c bearing urazoles, ss-dT₂₅ bound exclusively to 1c, and ss-dC₂₅ bound selectively to 1a (imidazolidin-2-one) and 1b (hydantoin). For the formation of pseudotriplets with duplex oligomers dA₂₅•dT₂₅ and dG₂₅•dC₂₅ at pH 7.4, d(A•T) pairs bound strongly to 1c but weakly to 1a and 1b. Conversely, d(G•C) pairs bound strongly to 1a and moderately to 1b and 1c. Under acidic conditions (pH 5.4), 1c exhibits the strongest binding, while 1a and 1b show moderate affinity. These findings highlight the potent binding capability and nucleobase selectivity of f-SWCNT 1c functionalized with urazoles. Biocompatibility is also assessed─touch responses and thrashing assays are performed to evaluate the ecotoxicity of shortened f-SWCNT 1c on the nervous system of C. elegans. No significant toxicity is observed up to concentrations of 250 μg/mL, with f-SWCNT 1c ∼2500-fold less toxic than simple SWCNT-COOH. These results suggest that the newly developed f-SWCNT 1c is not only highly biocompatible but also holds great promise for broad biological applications.

A novel codrug 1 is designed through the covalent conjugation of lenalidomide (2, an immunomodulatory agent) and paclitaxel (3, an anticancer drug) via...

There is a pressing need to develop fluorescent dyes with light emission peaks in the wavelength range of 650–950 nm for optical live‐cell imaging applications. The advancement of fluorescent dyes with a large Stokes shift is imperative for their biological applications. A novel domino reaction is developed with success for the synthesis of diverse 9a H ‐benzoquinolizines in 65–95% yields through reaction of α ‐silylaryl triflates, pyridine derivatives, and activated alkynes at room temperature. This single‐flask reaction involves completion of a 1,2‐elimination, a 1,2‐addition, and an intermolecular (4 + 2) cycloaddition in situ. Among 15 new products, diethyl 9a H ‐tribenzo[ c , f , h ]quinolizine‐1,2‐dicarboxylate with extension of π ‐conjugation is identified as the top‐performing dye. It shows near‐infrared fluorescent emission at 674 nm with the Stokes shift of 197 nm, ε _max = 5.62 × 10 ⁴ M ^–1 cm ^–1 , Φ _fl = 15.2%, and τ _av = 10.1 ns. It also exhibits excellent photostability with only 4.97% decomposed under irradiation with an Hg lamp for 60 min. With a remarkable 96 ± 2% viability, minimal toxicity toward CT‐26 cancer cells, and coupled with promising results from confocal microscopy, this 9a H ‐tribenzoquinolizine emerges as an ideal fluorescent dye for imaging live cells.

An innovative method was developed for the performance of aldol additions in an irreversible fashion by the use of calcium metal impregnated silica gel (Ca@SiO₂) as a remarkable reducing reagent. In this approach, Ca@SiO₂ drove the reaction forward, prevented reversibility, and ensured the formation of the desired products. Thus, in the presence of Ca@SiO₂ (3.0 equiv), aldehydes (1.0 equiv) condensed with ketones (1.0 equiv) in 2-MeTHF to yield α,β-unsaturated enones in 71-90% yields at 25 °C. Additionally, a domino reaction involving successive aldol addition, dehydration, and Michael addition was developed for the preparation of 1,5-diketones. Accordingly, when aldehydes (1.0 equiv) were allowed to react with ketones (2.2 equiv) and Ca@SiO₂(4.0 equiv), 1,5-diketones were produced in 67-88% yields. These reactions involved radical processes, where Ca@SiO₂ abstracted two α hydrogen atoms from ketones and the oxygen atom from aldehydes to form CaH₂@SiO₂ and CaO@SiO₂, respectively. These species were confirmed by powder X-ray diffraction analysis. The resultant impregnated silica gel species were solid and insoluble in the reaction mixtures, which made the addition reactions irreversible. This method represents a significant advancement in aldol condensation reactions and offers the advantages of both atom economy and atom efficiency.

On the basis of a “chemo-combination strategy”, (6-chloro)coumarin was incorporated to purines and pyrimidines, as well as their corresponding nucleosides, with a –SCH₂– linker at different positions under alkaline conditions. These conjugates were found to exert an antiviral effect on the 1b subgenomic replicon replication of the hepatitis C virus (HCV) in Huh 5-2 and Huh 9-13 cells. In this compound library containing 14 new compounds, 6-[(6′-chlorocoumarin-3′-yl)methylthio]purine, 6-(6′-chlorocoumarin-3′-yl)methylthio-9-(β-D-ribofuranos-1″-yl)purine, and 2-[(6′-chlorocoumarin-3′-yl)methylthio]uracil showed great inhibitory abilities, with EC₅₀ values between 6.6 and 9.4 μM and selectivity indexes >16–41. Moreover, the structure–activity relationship between purines and pyrimidines is elucidated, which reveals the critical factor of the attachment of the coumarin moiety at different positions in purines and pyrimidines.

This report presents our discoveries that include the successful hybridization of grafted single-walled carbon nanotubes (SWCNTs) with dsDNA to form pseudo triplex-DNA. These tubes are attached with distinctive five-membered N-containing heterocycles (i.e., imidazolidinone and triazolidindione) on their surface. In this study, the heterocycles play a crucial role as DNA binders. Consequently, three functionalized SWCNTs (f-SWCNTs) are synthesized, which are incorporated with multiple-phenoxy-triazole-(ethylene glycol)-(heterocycle) ligands. These f-SWCNTs are entwined with dsDNA to form "pseudo triplex". Notably, the dsDNA disengages from the f-SWCNTs at 85 °C and then is able to revert to triplex-DNA upon temperature reduction. Additionally, these f-SWCNTs act as a complementary strand for ssDNA to form pseudo duplex-DNA, in which the base pairings therein dissociate at 55 °C. Comprehensive analysis by use of CD spectrometer, SEM, TEM, and AFM microscopy provides substantive evidence for these phenomena. The demonstrated ability to manipulate DNA liberation from pseudo duplexes and triplexes indicates the potential versatility of f-SWCNTs as effective delivery vehicles for drugs and biomaterials in gene therapy and biotechnology.

A synthetic method was developed for the generation of a quaternary carbon center in carbonyl compounds. This innovative process involved the reaction of α-thiolate lactones and cycloalkanones with two equivalents of arynes in acetonitrile to give α,α-diarylated products in 63-85% yields at 25 °C. The reaction unfolds through an unconventional domino process, encompassing sequential 1,2-elimination, 1,2-nucleophilic addition, 1,4-proton transfer, the second 1,2-nucleophilic addition, interrupted Pummerer rearrangement, intramolecular spirocyclization, and sulfonium ring-opening. The potential of this "single-flask" reaction was systematically investigated and found well-suited to generate diarylated carbonyl compounds, incorporating naphthalene, pyridine, quinoline, or isoquinoline rings adorned with various substituents.

An ideal codrug design should be able to control drug release, offer selectivity during drug delivery, and break down into non-toxic fragments after biodegradation. Our design incorporates d-ribofuranose as the core, with carbamate and carbonate groups as linking joints, a phosphodiester moiety as an enzyme recognition site, and lenalidomide and paclitaxel as the constituent drugs. The codrug synthesis involves seven steps with a 33% overall yield. The target codrug increases its water solubility 685 times versus paclitaxel.

One of the primary concerns in the development of new chemical reactions pertains to the choice of solvents, many of which can have harmful ecological impacts. Additionally, a major portion of waste generated in the chemical and pharmaceutical industries comes from the solvents employed. The elimination of solvent usage is highly desirable for creation of environmentally friendly chemical processes as it leads to a substantial reduction in waste production. Accordingly, a novel neat reaction was developed for the synthesis of (β‐amino)nitriles as a prominent moiety through a domino process. It involved the use of silylphenyl triflates, Schiff bases, and acetonitrile (CH₃CN) in a 1 : 1 : 1 ratio, among which CH₃CN served as a starting material rather than a solvent. This reaction was initiated by caesium fluoride (CsF) to form an aryne through 1,2‐elimination followed by sequential 1,2‐addition, proton transfer, and a second 1,2‐addition. Complete conversion was carried out at 25 °C for 1.0 h to give (β‐amino)nitriles in 76–88 % yields. This solvent‐free reaction minimized waste production and reduced costs associated with extra reagents, solvents, and labour. It possesses a compelling E factor and impressive volume productivity. This reaction sets a new benchmark for solvent‐free aryne domino processes in green chemistry advancements.