Phosphorus-Doped Graphitic Carbon Nitride Nanotubes with Amino-rich Surface for Efficient CO₂ Capture, Enhanced Photocatalytic Activity, and Product Selectivity

Phosphorus-doped graphitic carbon nitrides (P-g-C₃N₄) have recently emerged as promising visible-light photocatalysts for both hydrogen generation and clean environment applications because of fast charge carrier transfer and increased light absorption. However, their photocatalytic performances on CO₂ reduction have gained little attention. In this work, phosphorus-doped g-C₃N₄ nanotubes are synthesized through the one-step thermal reaction of melamine and sodium hypophosphite monohydrate (NaH₂PO₂·H₂O). The phosphine gas generated from the thermal decomposition of NaH₂PO₂·H₂O induces the formation of P-g-C₃N₄ nanotubes from g-C₃N₄ nanosheets, leads to an enlarged BET surface area and a unique mesoporous structure, and creates an amino-rich surface. The interstitial doping phosphorus also down shifts the conduction and valence band positions and narrows the band gap of g-C₃N₄. The photocatalytic activities are dramatically enhanced in the reduction both of CO₂ to produce CO and CH₄ and of water to produce H₂ because of the efficient suppression of the recombination of electrons and holes. The CO₂ adsorption capacity is improved to 3.14 times, and the production of CO and CH₄ from CO₂ increases to 3.10 and 13.92 times that on g-C₃N₄, respectively. The total evolution ratio of CO/CH₄ dramatically decreases to 1.30 from 6.02 for g-C₃N₄, indicating a higher selectivity of CH₄ product on P-g-C₃N₄, which is likely ascribed to the unique nanotubes structure and amino-rich surface

Femtomolar Inhibitors Bind to 5′-Methylthioadenosine Nucleosidases with Favorable Enthalpy and Entropy

5′-Methylthioadenosine/<i>S</i>-adenosylhomocysteine nucleosidase (MTAN) catalyzes the hydrolytic cleavage of adenine from methylthioadenosine (MTA). Inhibitor design and synthesis informed by transition state analysis have developed femtomolar inhibitors for MTANs, among the most powerful known noncovalent enzyme inhibitors. Thermodynamic analyses of the inhibitor binding reveals a combination of highly favorable contributions from enthalpic (−24.7 to −4.0 kcal mol^–1) and entropic (−10.0 to 6.4 kcal mol^–1) interactions. Inhibitor binding to similar MTANs from different bacterial species gave distinct energetic contributions from similar catalytic sites. Thus, binding of four transition state analogues to <i>Ec</i>MTAN and <i>Se</i>MTAN is driven primarily by enthalpy, while binding to <i>Vc</i>MTAN is driven primarily by entropy. Human MTA phosphorylase (<i>h</i>MTAP) has a transition state structure closely related to that of the bacterial MTANs, and it binds tightly to some of the same transition state analogues. However, the thermodynamic signature of binding of an inhibitor to <i>h</i>MTAP differs completely from that with MTANs. We conclude that factors other than first-sphere catalytic residue contacts contribute to binding of inhibitors because the thermodynamic signature differs between bacterial species of the same enzyme

Effect of treatment with immucillins IA, IH and SMIH on the cellular ultrastructure of <i>L</i>. <i>(L</i>.<i>) infantum chagasi</i> promastigotes.

<p>Promastigotes were cultured in the absence (A, B) or in the presence of the immucillins IA (C), IH (D) or SMIH (E and F) at a 10 μM concentration and examined by transmission electron microscopy. The untreated controls show the intact full cell structure. Cells treated with the inhibitors show morphological alterations.</p

Effect of daily addition of immucillins on <i>L</i>. <i>(L</i>.<i>) infantum chagasi</i> promastigote replication.

<p>Immucillins IA, IH (0.05 to 250 μM concentration) and SMIH (0.01nM to 25nM concentration) were added in culture at 0h, 24h and 48h. The parasite replication was monitored daily. Promastigotes with no addition were included as control. The <i>y</i> axis represents the number of promastigotes x 10⁴/ml. Data shown are the mean ± SE of two independent experiments performed in triplicate.</p

Immucillins Impair <i>Leishmania (L</i>.<i>) infantum chagasi</i> and <i>Leishmania (L</i>.<i>) amazonensis</i> Multiplication <i>In Vitro</i>

<div><p>Chemotherapy against visceral leishmaniasis is associated with high toxicity and drug resistance. <i>Leishmania</i> parasites are purine auxotrophs that obtain their purines from exogenous sources. Nucleoside hydrolases release purines from nucleosides and are drug targets for anti-leishmanial drugs, absent in mammal cells. We investigated the substrate specificity of the <i>Leishmania (L</i>.<i>) donovani</i> recombinant nucleoside hydrolase NH36 and the inhibitory effect of the immucillins IA (ImmA), DIA (DADMe-ImmA), DIH (DADMe-ImmH), SMIH (SerMe-ImmH), IH (ImmH), DIG (DADMe-ImmG), SMIG (SerMe-ImmG) and SMIA (SerME-ImmA) on its enzymatic activity. The inhibitory effects of immucillins on the <i>in vitro</i> multiplication of <i>L</i>. <i>(L</i>.<i>) infantum chagasi</i> and <i>L</i>. <i>(L</i>.<i>) amazonensis</i> promastigotes were determined using 0.05–500 μM and, when needed, 0.01–50 nM of each drug. The inhibition on multiplication of <i>L</i>. <i>(L</i>.<i>) infantum chagasi</i> intracellular amastigotes <i>in vitro</i> was assayed using 0.5, 1, 5 and 10 μM of IA, IH and SMIH. The NH36 shows specificity for inosine, guanosine, adenosine, uridine and cytidine with preference for adenosine and inosine. IA, IH, DIH, DIG, SMIH and SMIG immucillins inhibited <i>L</i>. <i>(L</i>.<i>) infantum chagasi</i> and <i>L</i>. <i>(L</i>.<i>) amazonensis</i> promastigote growth <i>in vitro</i> at nanomolar to micromolar concentrations. Promastigote replication was also inhibited in a chemically defined medium without a nucleoside source. Addition of adenosine decreases the immucillin toxicity. IA and IH inhibited the NH36 enzymatic activity (<i>Ki</i> = 0.080 μM for IA and 0.019 μM for IH). IA, IH and SMIH at 10 μM concentration, reduced the <i>in vitro</i> amastigote replication inside mice macrophages by 95% with no apparent effect on macrophage viability. Transmission electron microscopy revealed global alterations and swelling of <i>L</i>. <i>(L</i>.<i>) infantum chagasi</i> promastigotes after treatment with IA and IH while SMIH treatment determined intense cytoplasm vacuolization, enlarged vesicles and altered kinetoplasts. Our results suggest that IA, IH and SMIH may provide new chemotherapy agents for leishmaniasis.</p></div

Effect of immucillins IA, DIA, IH, DIH, IH, SMIH, DIG, SerMe-ImmG and Ser-Me ImmA on the growth rate of <i>Leishmania (L.) infantum chagasi</i> in acellular medium.

<p>The growth of parasites cultured at 26°C in the absence (no addition control) or the presence of the immucillins assayed in concentrations ranging from 1 to 500 μM and in the presence of immucillin SMIH tested in concentrations from 0.05 to 50 nM. The inhibitors were added at 0 hour and the parasites were counted daily. The <i>y</i> axis represent the number of promastigotes x 10⁷/ml of liquid medium. Data shown are the mean ± SE of two independent experiments performed in triplicate.</p

Chemical structure of the immucillins assayed for inhibition of <i>Leishmania</i> multiplication: IA (ImmA), DIA (DADMe-ImmA), DIH (DADMe-ImmH), SMIH (SerMe-ImmH), IH (ImmH), DIG (DADMe-ImmG), SMIG (SerMe-ImmG) and SMIA (SerMe-ImmA).

<p>Chemical structure of the immucillins assayed for inhibition of <i>Leishmania</i> multiplication: IA (ImmA), DIA (DADMe-ImmA), DIH (DADMe-ImmH), SMIH (SerMe-ImmH), IH (ImmH), DIG (DADMe-ImmG), SMIG (SerMe-ImmG) and SMIA (SerMe-ImmA).</p

Effect of immucillins IA, IH and SMIH on the replication of intracellular amastigotes of <i>L</i>. <i>(L</i>.<i>) infantum chagasi</i>.

<p>Immucillins and Glucantime were added at 0 hour (A), at a 10μM concentration, to peritoneal macrophages incubated <i>in vitro</i> and macrophage viability was assessed by the method of Trypan blue at 48h, or the drugs were added at 0, 24 and 48 h (B) and viability was assessed at 72h. Peritoneal macrophages were infected with promastigotes of <i>L</i>. <i>(L</i>.<i>) infantum chagasi</i> and a dose of each immucillin (10 μM) was added at 0 hour (C) or at 0, 24 and 48 h (D) and the phagocytic index (percent of infected macrophages <i>x</i> average number of intracellular amastigotes) was determined at 72h. Data shown are the mean ± SE of two independent experiments performed in triplicate. Macrophages treated with 10 μM Glucantime were used as controls.</p

Effect of immucillins IA, DIA, IH, DIH, IH, SMIH, DIG, SerMe-ImmG and Ser-Me ImmA on the growth rate of <i>Leishmania (L.) amazonensis</i> in acellular medium.

<p>The growth of parasites cultured at 26°C in the absence (no addition control) or the presence of the immucillins assayed in concentrations ranging from 1 to 500 μM and in the presence of immucillin SMIH tested in concentrations from 0.05 to 50 nM. The inhibitors were added at 0 hour and the parasites were counted daily. The <i>y</i> axis represent the number of promastigotes x 10⁷/ml of liquid medium. Data shown are the mean ± SE of two independent experiments performed in triplicate.</p

Kinetic parameters for Nucleoside hydrolase NH36 of <i>L</i>. <i>(L</i>.<i>) donovani</i>.

<p>Initial reaction rates were measured under conditions described under “Materials and Methods.” The kinetic parameters and associated errors were determined with fits of the data to the Michaelis-Menten equation.</p><p>Kinetic parameters for Nucleoside hydrolase NH36 of <i>L</i>. <i>(L</i>.<i>) donovani</i>.</p