The Leaving Group Strongly Affects H₂O₂‑Induced DNA Cross-Linking by Arylboronates

We evaluated the effects of the benzylic leaving group and core structure of arylboronates on H₂O₂-induced formation of bisquinone methides for DNA interstrand cross-linking. The mechanism of DNA cross-linking induced by these arylboronates involves generation of phenol intermediates followed by departure of benzylic leaving groups leading to QMs which directly cross-link DNA via alkylation. The QM formation is the rate-determining step for DNA cross-linking. A better leaving group (Br) and stepwise bisquinone methide formation increased interstrand cross-linking efficiency. These findings provide essential guidelines for designing novel anticancer prodrugs

The Leaving Group Strongly Affects H₂O₂‑Induced DNA Cross-Linking by Arylboronates

We evaluated the effects of the benzylic leaving group and core structure of arylboronates on H₂O₂-induced formation of bisquinone methides for DNA interstrand cross-linking. The mechanism of DNA cross-linking induced by these arylboronates involves generation of phenol intermediates followed by departure of benzylic leaving groups leading to QMs which directly cross-link DNA via alkylation. The QM formation is the rate-determining step for DNA cross-linking. A better leaving group (Br) and stepwise bisquinone methide formation increased interstrand cross-linking efficiency. These findings provide essential guidelines for designing novel anticancer prodrugs

The Leaving Group Strongly Affects H₂O₂‑Induced DNA Cross-Linking by Arylboronates

We evaluated the effects of the benzylic leaving group and core structure of arylboronates on H₂O₂-induced formation of bisquinone methides for DNA interstrand cross-linking. The mechanism of DNA cross-linking induced by these arylboronates involves generation of phenol intermediates followed by departure of benzylic leaving groups leading to QMs which directly cross-link DNA via alkylation. The QM formation is the rate-determining step for DNA cross-linking. A better leaving group (Br) and stepwise bisquinone methide formation increased interstrand cross-linking efficiency. These findings provide essential guidelines for designing novel anticancer prodrugs

The Leaving Group Strongly Affects H₂O₂‑Induced DNA Cross-Linking by Arylboronates

We evaluated the effects of the benzylic leaving group and core structure of arylboronates on H₂O₂-induced formation of bisquinone methides for DNA interstrand cross-linking. The mechanism of DNA cross-linking induced by these arylboronates involves generation of phenol intermediates followed by departure of benzylic leaving groups leading to QMs which directly cross-link DNA via alkylation. The QM formation is the rate-determining step for DNA cross-linking. A better leaving group (Br) and stepwise bisquinone methide formation increased interstrand cross-linking efficiency. These findings provide essential guidelines for designing novel anticancer prodrugs

The Leaving Group Strongly Affects H₂O₂‑Induced DNA Cross-Linking by Arylboronates

We evaluated the effects of the benzylic leaving group and core structure of arylboronates on H₂O₂-induced formation of bisquinone methides for DNA interstrand cross-linking. The mechanism of DNA cross-linking induced by these arylboronates involves generation of phenol intermediates followed by departure of benzylic leaving groups leading to QMs which directly cross-link DNA via alkylation. The QM formation is the rate-determining step for DNA cross-linking. A better leaving group (Br) and stepwise bisquinone methide formation increased interstrand cross-linking efficiency. These findings provide essential guidelines for designing novel anticancer prodrugs

Unusual Si–H Bond Activation and Formation of Cationic Scandium Amide Complexes from a Mono(amidinate)-Ligated Scandium Bis(silylamide) Complex and Their Performance in Isoprene Polymerization

Amine elimination of scandium tris­(silylamide) complex Sc­[N­(SiHMe₂)₂]₃(THF) with 1 equiv of the amidine [PhC­(N-2,6-^<i>i</i>Pr₂C₆H₃)₂]H in toluene afforded the neutral mono­(amidinate) scandium bis­(silylamide) complex [PhC­(N-2,6-^<i>i</i>Pr₂C₆H₃)₂]­Sc­[N­(SiHMe₂)₂]₂ (<b>1</b>) in 93% isolated yield. When <b>1</b> was activated with 1 equiv of [Ph₃C]­[B­(C₆F₅)₄] in the presence of THF, the unexpected cationic amidinate scandium amide complex [{PhC­(N-2,6-^<i>i</i>Pr₂C₆H₃)₂}­ScN­{SiHMe₂}­{SiMe₂N­(SiHMe₂)₂}­(THF)₂]­[B­(C₆F₅)₄] (<b>2</b>) was generated. Treatment of <b>1</b> with excess AlMe₃ gave the Sc/Al heterometallic methyl complex [PhC­(N-2,6-^<i>i</i>Pr₂C₆H₃)₂]­Sc­[(μ-Me)₂AlMe₂]₂ (<b>3</b>). All these complexes were well-characterized by elemental analysis, NMR spectroscopy, and X-ray crystallography. The combination <b>1</b>/[Ph₃C]­[B­(C₆F₅)₄] in toluene showed activity toward isoprene polymerization. Addition of excess AlMe₃ to the <b>1</b>/[Ph₃C]­[B­(C₆F₅)₄] catalyst system switched the regioselectivity of isoprene polymerization from 3,4-specific to cis-1,4-selective

Unusual Si–H Bond Activation and Formation of Cationic Scandium Amide Complexes from a Mono(amidinate)-Ligated Scandium Bis(silylamide) Complex and Their Performance in Isoprene Polymerization

Amine elimination of scandium tris­(silylamide) complex Sc­[N­(SiHMe₂)₂]₃(THF) with 1 equiv of the amidine [PhC­(N-2,6-^<i>i</i>Pr₂C₆H₃)₂]H in toluene afforded the neutral mono­(amidinate) scandium bis­(silylamide) complex [PhC­(N-2,6-^<i>i</i>Pr₂C₆H₃)₂]­Sc­[N­(SiHMe₂)₂]₂ (<b>1</b>) in 93% isolated yield. When <b>1</b> was activated with 1 equiv of [Ph₃C]­[B­(C₆F₅)₄] in the presence of THF, the unexpected cationic amidinate scandium amide complex [{PhC­(N-2,6-^<i>i</i>Pr₂C₆H₃)₂}­ScN­{SiHMe₂}­{SiMe₂N­(SiHMe₂)₂}­(THF)₂]­[B­(C₆F₅)₄] (<b>2</b>) was generated. Treatment of <b>1</b> with excess AlMe₃ gave the Sc/Al heterometallic methyl complex [PhC­(N-2,6-^<i>i</i>Pr₂C₆H₃)₂]­Sc­[(μ-Me)₂AlMe₂]₂ (<b>3</b>). All these complexes were well-characterized by elemental analysis, NMR spectroscopy, and X-ray crystallography. The combination <b>1</b>/[Ph₃C]­[B­(C₆F₅)₄] in toluene showed activity toward isoprene polymerization. Addition of excess AlMe₃ to the <b>1</b>/[Ph₃C]­[B­(C₆F₅)₄] catalyst system switched the regioselectivity of isoprene polymerization from 3,4-specific to cis-1,4-selective

Photochemical Generation of Benzyl Cations That Selectively Cross-Link Guanine and Cytosine in DNA

UV irradiation of several aryl boronates efficiently produced bifunctional benzyl cations that selectively form guanine-cytosine cross-links in DNA. Photoinduced homolysis of the C–Br bond took place with the aryl boronate bromides <b>3a</b> and <b>4a</b>, generating free radicals that were oxidized to benzyl cations via electron transfer. However, photoirradiation of the quaternary ammonium salts <b>3b</b> and <b>4b</b> led to heterolysis of C–N bond, directly producing benzyl cations. The electron-donating group in the aromatic ring greatly enhanced cross-linking efficiency

Identification of Rabbit Annulus Fibrosus-Derived Stem Cells

<div><p>Annulus fibrosus (AF) injuries can lead to substantial deterioration of intervertebral disc (IVD) which characterizes degenerative disc disease (DDD). However, treatments for AF repair/regeneration remain challenging due to the intrinsic heterogeneity of AF tissue at cellular, biochemical, and biomechanical levels. In this study, we isolated and characterized a sub-population of cells from rabbit AF tissue which formed colonies <i>in vitro</i> and could self-renew. These cells showed gene expression of typical surface antigen molecules characterizing mesenchymal stem cells (MSCs), including CD29, CD44, and CD166. Meanwhile, they did not express negative markers of MSCs such as CD4, CD8, and CD14. They also expressed Oct-4, nucleostemin, and SSEA-4 proteins. Upon induced differentiation they showed typical osteogenesis, chondrogenesis, and adipogenesis potential. Together, these AF-derived colony-forming cells possessed clonogenicity, self-renewal, and multi-potential differentiation capability, the three criteria characterizing MSCs. Such AF-derived stem cells may potentially be an ideal candidate for DDD treatments using cell therapies or tissue engineering approaches.</p></div

Induced differentiation of AF-derived colony forming cells.

<p>(<b>A</b>–<b>B</b>) Osteogenic differentiation at 3 weeks. Mineralization was stained with Alizarin red S (<b>A</b>). Expression of osteocyte-specific genes, including <i>Runx-2</i> and <i>Col I</i>, were up-regulated in induced cells as analyzed by RT-PCR (<b>B</b>). (<b>C</b>–<b>D</b>) Chondrogenic differentiation at 3 weeks. Cells were stained with Safranin O (<b>C</b>). Expression of chondrocyte-specific genes <i>Sox-9</i> and <i>Col II</i> levels was higher in induced cells (<b>D</b>). (<b>E</b>–<b>F</b>) Adipogenic differentiation at 2 weeks. Secretion of oil droplets (<b>E</b>) and expression of adipocyte-specific genes <i>PPAR-γ</i> and <i>LPL</i> (<b>F</b>) were higher in induced cells.</p