Synthesis, Structures, and Reactivity of Cyclometalated Complexes Formed by Insertion of Alkynes into M–C (M = Ir and Rh) Bonds

Reactions of three aryl-substituted phosphines with [Cp*MCl₂]₂ (M = Ir and Rh) have been carried out in the presence of sodium acetate. Aryl-substituted phosphine is cyclometalated readily to give the corresponding five-membered metallacycle complex via an intramolecular activation of C­(sp²)–H or C­(sp³)–H bond. Competition reaction indicates that the aromatic C­(sp²)–H bond is more likely to be activated than C­(sp³)–H bond under the same conditions. As representatives of cyclometalated complexes containing an M–C­(sp²) bond, cycloiridated complex <b>1</b> and cyclorhodated complex <b>3</b> reacted with DMAD to afford corresponding seven-membered cyclometalated complexes <b>13</b> and <b>14</b> via 1,2-insertion of alkyne into M–C bond. However, the reaction of <b>1</b> with diphenylacetylene or phenylacetylene resulted in five-membered and six-membered doubly cycloiridated complexes <b>15</b> or <b>16</b>, the formation of which presumably went through the vinylidene rearrangement of alkynes followed by 1,1-insertion; while the reaction of <b>3</b> with diphenylacetylene or phenylacetylene mainly gave normal seven-membered cyclorhodated complexes <b>17</b> or <b>18</b> by 1,2-insertion. For two representatives of cyclometalated complexes comprising an M–C­(sp³) bond, cycloiridated complex <b>4</b> and cyclorhodated complex <b>6</b> reacted with DMAD to form corresponding seven-membered cyclometalated complexes <b>20</b> and <b>21</b> by 1,2-insertion. Interestingly, the reactions of <b>4</b> and <b>6</b> with phenylacetylene generated six-membered metallacycle complexes <b>22</b> and <b>23</b>, and a plausible formation pathway is the similar 1,1-insertion of vinylidene ligand into the M–C bond followed by the isomerization of the C–C double bond. Molecular structures of five-membered cyclometalated complexes <b>4</b> and <b>5</b> and insertion products <b>13</b>, <b>15</b>–<b>19</b>, <b>21</b>, and <b>22</b> were determined by X-ray diffraction

Synthesis, Structures, and Reactivity of Cyclometalated Complexes Formed by Insertion of Alkynes into M–C (M = Ir and Rh) Bonds

Reactions of three aryl-substituted phosphines with [Cp*MCl₂]₂ (M = Ir and Rh) have been carried out in the presence of sodium acetate. Aryl-substituted phosphine is cyclometalated readily to give the corresponding five-membered metallacycle complex via an intramolecular activation of C­(sp²)–H or C­(sp³)–H bond. Competition reaction indicates that the aromatic C­(sp²)–H bond is more likely to be activated than C­(sp³)–H bond under the same conditions. As representatives of cyclometalated complexes containing an M–C­(sp²) bond, cycloiridated complex <b>1</b> and cyclorhodated complex <b>3</b> reacted with DMAD to afford corresponding seven-membered cyclometalated complexes <b>13</b> and <b>14</b> via 1,2-insertion of alkyne into M–C bond. However, the reaction of <b>1</b> with diphenylacetylene or phenylacetylene resulted in five-membered and six-membered doubly cycloiridated complexes <b>15</b> or <b>16</b>, the formation of which presumably went through the vinylidene rearrangement of alkynes followed by 1,1-insertion; while the reaction of <b>3</b> with diphenylacetylene or phenylacetylene mainly gave normal seven-membered cyclorhodated complexes <b>17</b> or <b>18</b> by 1,2-insertion. For two representatives of cyclometalated complexes comprising an M–C­(sp³) bond, cycloiridated complex <b>4</b> and cyclorhodated complex <b>6</b> reacted with DMAD to form corresponding seven-membered cyclometalated complexes <b>20</b> and <b>21</b> by 1,2-insertion. Interestingly, the reactions of <b>4</b> and <b>6</b> with phenylacetylene generated six-membered metallacycle complexes <b>22</b> and <b>23</b>, and a plausible formation pathway is the similar 1,1-insertion of vinylidene ligand into the M–C bond followed by the isomerization of the C–C double bond. Molecular structures of five-membered cyclometalated complexes <b>4</b> and <b>5</b> and insertion products <b>13</b>, <b>15</b>–<b>19</b>, <b>21</b>, and <b>22</b> were determined by X-ray diffraction

Synthesis, Structures, and Reactivity of Single and Double Cyclometalated Complexes Formed by Reactions of [Cp*MCl₂]₂ (M = Ir and Rh) with Dinaphthyl Phosphines

Reactions of two dinaphthyl phosphines with [Cp*IrCl₂]₂ have been carried out. In the case of di­(α-naphthyl)­phenylphosphine (<b>1a</b>), a simple P-coordinated neutral adduct <b>2a</b> is obtained. However, <i>tert</i>-butyldi­(α-naphthyl)­phenylphosphine (<b>1b</b>) is cyclometalated to form [Cp*IrCl­(P^C)] (<b>3b</b>). Complexes <b>2a</b> and <b>3a</b> undergo further cyclometalation to give the corresponding double cyclometalated complexes [Cp*Ir­(C^P^C)] (<b>4a</b>,<b>b</b>) upon heating. In the presence of sodium acetate, reactions of <b>1a</b>,<b>b</b> with [Cp*IrCl₂]₂ directly afford the final double cyclometalated complexes (<b>4a</b>,<b>b</b>). In the absence of acetate, [Cp*RhCl₂]₂ shows no reaction with <b>1a</b>,<b>b</b>, whereas with acetate the reactions form the corresponding single cyclometalated complexes [Cp*RhCl­(P^C)] (<b>5a</b>,<b>b</b>), which react with ^<i>t</i>BuOK to form the corresponding rhodium hydride complexes (<b>6a</b>,<b>b</b>). Treatment of <b>4a</b> with CuCl₂ or I₂ leads to opening of two Ir–C σ bonds to yield the corresponding P-coordinated iridium dihalide (<b>7</b> or <b>8</b>) by means of an intramolecular C–C coupling reaction. A new chiral phosphine (<b>11</b>) is formed by the ligand-exchange reaction of <b>8</b> with PMe₃. Reactions of the single cycloiridated complex <b>3b</b> with terminal aromatic alkynes result in the corresponding five- and six-membered doubly cycloiridated complex <b>12</b> and/or η²-alkene coordinated complexes <b>13–15</b>; the latter discloses that the electronic effect of terminal alkynes affects the regioselectivity. While the single cyclorhodated complex <b>5b</b> reacts with terminal aromatic alkynes to form the corresponding six-membered cyclometalated complexes <b>16a–c</b> by vinylidene rearrangement/1,1-insertion. Plausible pathways for formation of insertion products <b>13–16</b> were proposed. Molecular structures of twelve new complexes were determined by X-ray diffraction

Overall effect of direct and indirect interactions on enrichment of experimentally validated MDAs.

<p>(<b>A</b>) Increasing the number miRNA-targeted DG enrichments for true MDAs in the whole set of putative MDAs. (<b>B</b>) Comparably, higher PIS value only slightly enriches for true MDAs. MDA: miRNA-disease association; DG: disease-related gene; PIS: protein interaction score.</p

Pro-apoptotic effect of miR-24 in SKOV3 cells.

<p>(<b>A</b>, <b>B</b> and <b>C</b>) Effect of transfection of different concentrations of miR-24 on cell viability of SKOV3 cells (n = 7). ** <i>p</i> < 0.01, *** <i>p</i> < 0.001 versus NC; (<b>D</b>) Transfection of 100 nM miR-24 induced cell apoptosis of SKOV3 cells (TUNEL assay, n = 5). *** <i>p</i> < 0.001 versus NC. (<b>E</b>) Transfection of 100 nM miR-24 resulted in cell apoptosis of SKOV3 cells (flow cytometry assay, n = 3). *** <i>p</i> < 0.001 versus NC. NC: negative control cells that were transfected with scramble miRNA.</p

Pro-apoptotic effect of miR-24 in A2780 cells.

<p>(<b>A)</b> Effect of transfection of 100 nM miR-24 on cell viability of A2780 cells (n = 7). *** <i>p</i> < 0.001 versus NC; (<b>B</b>) Transfection of 100 nM miR-24 induced cell apoptosis of A2780 cells (TUNEL assay, n = 5). *** <i>p</i> < 0.001 versus NC. (<b>C</b>) Transfection of miR-24 reduced the CDK4 and <i>p</i>-MDM2 protein level but enhanced the expression of p53 (Western blot assay, n = 3). ** <i>p</i> < 0.05, ** <i>p</i> < 0.01, *** <i>p</i> < 0.001 versus NC. NC: negative control cells that were transfected with scramble miRNA; NS: No significant difference was found between Ctrl group and NC group.</p

Comparison of the number of true MDAs between miRNAs with < 10 target genes and those with ≥ 10 target genes.

<p>(<b>A</b>) MiRNAs with ≥ 10 target genes are involved with more true MDAs than those targeting less target genes. *** <i>p</i> < 0.001 versus < 10; (<b>B</b>) Box-and-whisker plots of the number of target genes for the two groups.</p