Enrolling Reactive Oxygen Species in Photon-To-Chemical Energy Conversion: Fundamentals, Technological Advances, and Applications

In theory, oxygen (O2) is an ideal chemical reagent because of its high relative abundance and negligible environmental toxicity. In practice however, by the nature of its ground state electronic configuration, many chemical reactions involving O2 are spin forbidden which dramatically decreases its reactivity and thus its utility in applications. More reactive forms of O2 can be achieved by changing its electronic configuration through the use of photochemical and photophysical methods. This review highlights the roll of photon-to-chemical energy conversion in two of these reactive oxygen species (ROS): superoxide (O2−) and singlet oxygen (1O2), which can be accessed through a number of photochemical methods and used in a variety of exciting applications. The theory behind ROS is introduced as produced using light irradiation. Then applications of these methods for chemical transformations are explored

The Multifunctional Dopamine D/D Receptor Agonists Also Possess Inhibitory Activity Against the Full-Length Tau441 Protein Aggregation

Neurodegeneration leads to variety of diseases which are linked to aberrant protein or peptide aggregation, as a one possible mechanism. Hence, small drug molecules targeting aggregation are of interest. Tau protein aggregation is one of the biomarkers of neurodegenerative diseases and is a viable drug target. Toward multifunctional inhibitors, we aim to incorporate structural elements in a potential drug in order to preserve dopamine agonist activity, which elevates disease symptoms associated with motor skills, and promote inhibitory activity against aggregation of the full-length tau (2N4R, tau441) protein. In our design, we introduced various moieties (catechol, non-catechol, biphenyl, piperazine, and thiazole) to determine which functional group leads to the greatest aggregation inhibition of tau. In vitro, tau aggregation was induced by heparin and monitored by using fluorescence aggregation assay, transmission electron microscopy and 4,4\u27-Dianilino-1,1\u27-binaphthyl-5,5\u27-disulfonic acid dipotassium salt (Bis-ANS) fluorescence spectroscopy. The catechol containing compounds, D-519 and D-520, prevented aggregation of tau. By contrast, non-catechol and thiazole containing compounds (D-264 and D-636) were poor inhibitors. The Bis-ANS studies revealed that the potent inhibitors bound solvent-exposed hydrophobic sites. Based on the density functional theory calculations on inhibitors tested, the compounds characterized with the high polarity and polarizability were more effective aggregation inhibitors. These findings could lead to the development of small multifunctional drug inhibitors for the treatment of tau-associated neurodegeneration

Tellurorhodamine Photocatalyzed Aerobic Oxidation of Organo-silanes and Phosphines by Visible-light

Tellurorhodamine, 9-mesityl-3,6-bis(dimethylamino)telluroxanthylium hexafluorophosphate (1), photocatalytically oxidizes aromatic and aliphatic silanes and triphenyl phosphine under mild aerobic conditions. Under irradiation with visible light, 1 can react with self-sensitized 1O2 to generate the active telluroxide oxidant (2). Silanes are oxidized to silanols and triphenyl phosphine is oxidized to triphenyl phoshine oxide either using 2, or 1 with aerobic irradiation. Kinetic experiments coupled with a computational study elucidate possible mechanisms of oxidation for both silane and phosphine substrates. First-order rates were observed in the oxidation of triphenyl phosphine and methyldiphenyl silane, indicating a substitution like mechanism for substrate binding to the oxidized tellurium(IV). Additionally, these reactions exhibited a rate-dependence on water. Oxidations were typically run in 50 : 50 water/methanol, however, the absence of water decreased the rates of silane oxidation to a greater degree than triphenyl phosphine oxidation. Parallel results were observed in solvent kinetic isotope experiments using D2O in the solvent mixture. The rates of oxidation were slowed to a greater degree in silane oxidation by 2 (kH/kD = 17.30) than for phosphine (kH/kD = 6.20). Various silanes and triphenyl phosphine were photocatalytically oxidized with 1 (5%) under irradiation with warm white LEDs using atmospheric oxygen as the terminal oxidant

Photocatalytic Aerobic Thiol Oxidation with a Self-Sensitized Tellurorhodamine Chromophore

Aerobic oxidation of thiols to disulfides was achieved photocatalytically using a tellurorhodamine chromophore (9-mesityl-3,6-bis(dimethylamino)telluroxanthylium hexafluorophosphate) as both the sensitizer and catalyst. The proposed mechanism, supported experimentally and computationally with DFT, involves the formation of a tellurorhodamine telluroxide from reaction with water and singlet oxygen generated by irradiation of the tellurorhodamine. The oxidation to the telluroxide is accompanied by the formation of hydrogen peroxide. The telluroxide oxidizes thiols to regenerate the tellurorhodamine and the disulfide plus water. Mechanistically, DFT suggests adding two thiols to the telluroxide with the loss of H2O to give a trigonal-bipyramidal Te(IV), which undergoes concerted loss of disulfide to regenerate 1. Oxidation of thiophenol and 2-naphthalenethiol was complete after 2 h of irradiation with visible light under atmospheric conditions. Oxidation of the electron-poor 2,6-dichlorothiophenol, the sterically bulky tert-butylmercaptan, and aliphatic dodecanethiol was slower. The two aliphatic thiols displayed competing catalyst degradation. The corresponding selenorhodamine chromophore (9-mesityl-3,6-bis(dimethylamino)selenoxanthylium hexafluorophosphate) does not form the corresponding selenoxide under similar conditions and photooxidizes thiophenol and 2-naphthalenethiol much more slowly (≤6% conversion after 2–3 h)

Immune response to the hepatitis B antigen in the RTS,S/AS01 malaria vaccine, and co-administration with pneumococcal conjugate and rotavirus vaccines in African children: A randomized controlled trial

The RTS,S/AS01 malaria vaccine (Mosquirix) reduces the incidence of Plasmodium falciparum malaria and is intended for routine administration to infants in Sub-Saharan Africa. We evaluated the immunogenicity and safety of 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV; Synflorix) and human rotavirus vaccine (HRV; Rotarix) when co-administered with RTS,S/AS01 (www.clinicaltrials.gov NCT01345240) in African infants. 705 healthy infants aged 8–12 weeks were randomized to receive three doses of either RTS,S/AS01 or licensed hepatitis B (HBV; Engerix B) vaccine (control) co-administered with diphtheria-tetanus-acellular pertussis-Haemophilus influenzae type-b-conjugate vaccine (DTaP/Hib) and trivalent oral poliovirus vaccine at 8–12-16 weeks of age, because DTaP/Hib was not indicated before 8 weeks of age. The vaccination schedule can still be considered broadly applicable because it was within the age range recommended for EPI vaccination. PHiD-CV or HRV were either administered together with the study vaccines, or after a 2-week interval. Booster doses of PHiD-CV and DTaP/Hib were administered at age 18 months. Non-inferiority of anti-HBV surface antigen antibody seroprotection rates following co-administration with RTS,S/AS01 was demonstrated compared to the control group (primary objective). Pre-specified non-inferiority criteria were reached for PHiD-CV (for 9/10 vaccine serotypes), HRV, and aP antigens co-administered with RTS,S/AS01 as compared to HBV co-administration (secondary objectives). RTS,S/AS01 induced a response to circumsporozoite protein in all groups. Pain and low grade fever were reported more frequently in the PHiD-CV group co-administered with RTS,S/AS01 than PHiD-CV co-administered with HBV. No serious adverse events were considered to be vaccine-related. RTS,S/AS01 co-administered with pediatric vaccines had an acceptable safety profile. Immune responses to RTS,S/AS01 and to co-administered PHiD-CV, pertussis antigens and HRV were satisfactory

Detection of somatic mutations and HPV in the saliva and plasma of patients with head and neck squamous cell carcinomas

To explore the potential of tumor-specific DNA as a biomarker for head and neck squamous cell carcinomas (HNSCC), we queried DNA from saliva or plasma of 93 HNSCC patients. We searched for somatic mutations or human papillomavirus genes, collectively referred to as tumor DNA. When both plasma and saliva were tested, tumor DNA was detected in 96% of 47 patients. The fractions of patients with detectable tumor DNA in early- and late-stage disease were 100% (n = 10) and 95% (n = 37), respectively. When segregated by site, tumor DNA was detected in 100% (n = 15), 91% (n = 22), 100% (n = 7), and 100% (n = 3) of patients with tumors of the oral cavity, oropharynx, larynx, and hypopharynx, respectively. In saliva, tumor DNA was found in 100% of patients with oral cavity cancers and in 47 to 70% of patients with cancers of the other sites. In plasma, tumor DNA was found in 80% of patients with oral cavity cancers, and in 86 to 100% of patients with cancers of the other sites. Thus, saliva is preferentially enriched for tumor DNA from the oral cavity, whereas plasma is preferentially enriched for tumor DNA from the other sites. Tumor DNA in saliva was found postsurgically in three patients before clinical diagnosis of recurrence, but in none of the five patients without recurrence. Tumor DNA in the saliva and plasma appears to be a potentially valuable biomarker for detection of HNSCC

Detection of somatic mutations and HPV in the saliva and plasma of patients with head and neck squamous cell carcinomas

To explore the potential of tumor-specific DNA as a biomarker for head and neck squamous cell carcinomas (HNSCC), we queried DNA from saliva or plasma of 93 HNSCC patients. We searched for somatic mutations or human papillomavirus genes, collectively referred to as tumor DNA. When both plasma and saliva were tested, tumor DNA was detected in 96% of 47 patients. The fractions of patients with detectable tumor DNA in early- and late-stage disease were 100% (n = 10) and 95% (n = 37), respectively. When segregated by site, tumor DNA was detected in 100% (n = 15), 91% (n = 22), 100% (n = 7), and 100% (n = 3) of patients with tumors of the oral cavity, oropharynx, larynx, and hypopharynx, respectively. In saliva, tumor DNA was found in 100% of patients with oral cavity cancers and in 47 to 70% of patients with cancers of the other sites. In plasma, tumor DNA was found in 80% of patients with oral cavity cancers, and in 86 to 100% of patients with cancers of the other sites. Thus, saliva is preferentially enriched for tumor DNA from the oral cavity, whereas plasma is preferentially enriched for tumor DNA from the other sites. Tumor DNA in saliva was found postsurgically in three patients before clinical diagnosis of recurrence, but in none of the five patients without recurrence. Tumor DNA in the saliva and plasma appears to be a potentially valuable biomarker for detection of HNSCC