CO2 Activation with Manganese Tricarbonyl Complexes through an H-Atom Responsive Benzimidazole Ligand.

Herein, we report the synthesis and characterization of two manganese tricarbonyl complexes, MnI (HL)(CO)3 Br (1 a-Br) and MnI (MeL)(CO)3 Br (1 b-Br) (where HL=2-(2'-pyridyl)benzimidazole; MeL=1-methyl-2-(2'-pyridy)benzimidazole) and assayed their electrocatalytic properties for CO2 reduction. A redox-active pyridine benzimidazole ancillary ligand in complex 1 a-Br displayed unique hydrogen atom transfer ability to facilitate electrocatalytic CO2 conversion at a markedly lower reduction potential than that observed for 1 b-Br. Notably, a one-electron reduction of 1 a-Br yields a structurally characterized H-bonded binuclear Mn(I) adduct (2 a') rather than the typically observed Mn(0)-Mn(0) dimer, suggesting a novel method for CO2 activation. Combining advanced electrochemical, spectroscopic, and single crystal X-ray diffraction techniques, we demonstrate the use of an H-atom responsive ligand may reveal an alternative, low-energy pathway for CO2 activation by an earth-abundant metal complex catalyst.

A first glance into mixed phosphine-stibine moieties as protecting ligands for gold clusters.

Atomically precise gold clusters have attracted considerable research interest as their tunable structure-property relationships have resulted in widespread applications, from sensing and biomedicine to energetic materials and catalysis. In this article, the synthesis and optical properties of a novel [Au6(SbP3)2][PF6]2 cluster are reported. Despite the lack of spherical symmetry in the core, the cluster shows exceptional thermal and chemical stability. Detailed structural attributes and optical properties are evaluated experimentally and theoretically. This, to the best of our knowledge, is the first report of a gold cluster protected via synergistic multidentate coordination of stibine (Sb) and phosphine moieties (P). To further show that the latter moieties give a set of unique properties that differs from monodentate phosphine-protected [Au6(PPh3)6]2+, geometric structure, electronic structure, and optical properties are analyzed theoretically. In addition, this report also demonstrates the critical role of overall-ligand architecture in stabilizing mixed ligand-protected gold clusters.

Crystal Structure and Optical Properties of a Chiral Mixed Thiolate/Stibine-Protected Au18 Cluster.

We report the first example of a chiral mixed thiolate/stibine-protected gold cluster, formulated as Au18(S-Adm)8(SbPh3)4Br2 (where S-Adm = 1-adamantanethiolate). Single crystal X-ray crystallography reveals the origin of chirality in the cluster to be the introduction of the rotating arrangement of Au2(S-Adm)3 and Au(S-Adm)2 staple motifs on an achiral Au13 core and the subsequent capping of the remaining gold atoms by SbPh3 and Br- ligands. Interestingly, the structure and properties of this new Au18 cluster are found to be different from other reported achiral Au18 clusters and the only other stibine-protected [Au13(SbPh3)8Cl4]+ cluster. Detailed analyses on the geometric and electronic structures of the new cluster are carried out to gain insights into its optical properties as well as reactivity and stability of such mixed monolayer-protected clusters.

Selective photocatalytic hydroxylation and epoxidation reactions by an iron complex using water as the oxygen source.

The iron complex [(bTAML)FeIII-OH2]- (1) selectively catalyses the photocatalytic hydroxylation and epoxidation reactions of alkanes and alkenes, respectively, using water as the oxygen-atom source. Upon the oxidation of unactivated alkanes, which included several substrates including natural products, hydroxylation was observed mostly at the 3° C-H bonds with 3° : 2° selectivity up to ∼100 : 1. When alkenes were used as the substrates, epoxides were predominantly formed with high yields. In the presence of H218O, more than 90% of the 18O-labelled oxygen atoms were incorporated into the hydroxylated and epoxide product indicating that water was the primary oxygen source. Mechanistic studies indicate the formation of an active [{(bTAML)FeIV}2-µ-oxo]2- (2) dimer from the starting complex 1via PCET. The subsequent disproportionation of 2 upon addition of substrate, leading to the formation of FeV(O), renders the high selectivity observed in these reactions.

Selective C-H Bond Oxidation Catalyzed by the Fe-bTAML Complex: Mechanistic Implications.

Nonheme iron complexes bearing tetradentate N-atom-donor ligands with cis labile sites show great promise for chemoselective aliphatic C-H hydroxylation. However, several challenges still limit their widespread application. We report a mechanism-guided development of a peroxidase mimicking iron complex based on the bTAML macrocyclic ligand framework (Fe-bTAML: biuret-modified tetraamido macrocyclic ligand) as a catalyst to perform selective oxidation of unactivated 3° bonds with unprecedented regioselectivity (3°:2° of 110:1 for adamantane oxidation), high stereoretention (99%), and turnover numbers (TONs) up to 300 using mCPBA as the oxidant. Ligand decomposition pathways involving acid-induced demetalation were identified, and this led to the development of more robust and efficient Fe-bTAML complexes that catalyzed chemoselective C-H oxidation. Mechanistic studies, which include correlation of the product formed with the FeV(O) reactive intermediates generated during the reaction, indicate that the major pathway involves the cleavage of C-H bonds by FeV(O). When these oxidations were performed in the presence of air, the yield of the oxidized product doubled, but the stereoretention remained unchanged. On the basis of 18O labeling and other mechanistic studies, we propose a mechanism that involves the dual activation of mCPBA and O2 by Fe-bTAML, leading to formation of the FeV(O) intermediate. This high-valent iron oxo remains the active intermediate for most of the reaction, resulting in high regio- and stereoselectivity during product formation.

Reductive activation of O2 by a bioinspired Fe complex for catalytic epoxidation reactions.

Aerobic epoxidation of olefins catalyzed by iron complexes without the use of a sacrificial coreductant is unknown. We report the reductive activation of O2 by a bioinspired [(bTAML)FeIII(H2O)]- (1) complex to catalyze the epoxidation of alkenes with TONs of up to 80. Spectroscopic and kinetic evidence indicates the involvement of FeV(O) as the active oxidant during the reaction.

Spectroscopic and Reactivity Comparisons of a Pair of bTAML Complexes with FeV═O and FeIV═O Units.

In this report we compare the geometric and electronic structures and reactivities of [FeV(O)]- and [FeIV(O)]2- species supported by the same ancillary nonheme biuret tetraamido macrocyclic ligand (bTAML). Resonance Raman studies show that the Fe═O vibration of the [FeIV(O)]2- complex 2 is at 798 cm-1, compared to 862 cm-1 for the corresponding [FeV(O)]- species 3, a 64 cm-1 frequency difference reasonably reproduced by density functional theory calculations. These values are, respectively, the lowest and the highest frequencies observed thus far for nonheme high-valent Fe═O complexes. Extended X-ray absorption fine structure analysis of 3 reveals an Fe═O bond length of 1.59 Å, which is 0.05 Å shorter than that found in complex 2. The redox potentials of 2 and 3 are 0.44 V (measured at pH 12) and 1.19 V (measured at pH 7) versus normal hydrogen electrode, respectively, corresponding to the [FeIV(O)]2-/[FeIII(OH)]2- and [FeV(O)]-/[FeIV(O)]2- couples. Consistent with its higher potential (even after correcting for the pH difference), 3 oxidizes benzyl alcohol at pH 7 with a second-order rate constant that is 2500-fold bigger than that for 2 at pH 12. Furthermore, 2 exhibits a classical kinteic isotope effect (KIE) of 3 in the oxidation of benzyl alcohol to benzaldehyde versus a nonclassical KIE of 12 for 3, emphasizing the reactivity differences between 2 and 3.

Electrochemical Formation of FeV (O) and Mechanism of Its Reaction with Water During O-O Bond Formation.

A detailed electrochemical investigation of a series of iron complexes (biuret-modified tetraamido iron macrocycles FeIII -bTAML), including the first electrochemical generation of FeV (O), and demonstration of their efficacy as homogeneous catalysts for electrochemical water oxidation (WO) in aqueous medium are reported. Spectroelectrochemical and mass spectral studies indicated FeV (O) as the active oxidant, formed due to two redox transitions, which were assigned as FeIV (O)/FeIII (OH2 ) and FeV (O)/FeIV (O). The spectral properties of both of these high-valent iron oxo species perfectly match those of their chemically synthesised versions, which were thoroughly characterised by several spectroscopic techniques. The O-O bond-formation step occurs by nucleophilic attack of H2 O on FeV (O). A kinetic isotope effect of 3.2 indicates an atom-proton transfer (APT) mechanism. The reaction of chemically synthesised FeV (O) in CH3 CN and water was directly probed by electrochemistry and was found to be first-order in water. The pKa value of the buffer base plays a critical role in the rate-determining step by increasing the reaction rate several-fold. The electronic effect on redox potential, WO rates, and onset overpotential was studied by employing a series of iron complexes. The catalytic activity was enhanced by the presence of electron-withdrawing groups on the bTAML framework. Changing the substituents from OMe to NO2 resulted in an eightfold increase in reaction rate, while the overpotential increased threefold.

Electrocatalytic water oxidation by a molecular cobalt complex through a high valent cobalt oxo intermediate.

Biuret-modified tetraamidomacrocyclic cobalt complex [CoIII-bTAML]- is shown to catalyze electrochemical water oxidation at basic pH leading to the formation of O2. Electrochemical and spectroscopic studies indicate a high valent cobalt oxo intermediate isoelectronic to CoV(O) as the active oxidant. The kinetic isotope effect of 8.63 indicates an atom proton transfer mechanism.

Mechanism of Oxygen Atom Transfer from Fe(V)(O) to Olefins at Room Temperature.

In biological oxidations, the intermediate Fe(V)(O)(OH) has been proposed to be the active species for catalyzing the epoxidation of alkenes by nonheme iron complexes. However, no study has been reported yet that elucidates the mechanism of direct O-atom transfer during the reaction of Fe(V)(O) with alkenes to form the corresponding epoxide. For the first time, we study the mechanism of O-atom transfer to alkenes using the Fe(V)(O) complex of biuret-modified Fe-TAML at room temperature. The second-order rate constant (k2) for the reaction of different alkenes with Fe(V)(O) was determined under single-turnover conditions. An 8000-fold rate difference was found between electron-rich (4-methoxystyrene; k2 = 216 M(-1) s(-1)) and electron-deficient (methyl trans-cinnamate; k2 = 0.03 M(-1) s(-1)) substrates. This rate difference indicates the electrophilic character of Fe(V)(O). The use of cis-stilbene as a mechanistic probe leads to the formation of both cis- and trans-stilbene epoxides (73:27). This suggests the formation of a radical intermediate, which would allow C-C bond rotation to yield both stereoisomers of stilbene-epoxide. Additionally, a Hammett ρ value of -0.56 was obtained for the para-substituted styrene derivatives. Detailed DFT calculations show that the reaction proceeds via a two-step process through a doublet spin surface. Finally, using biuret-modified Fe-TAML as the catalyst and NaOCl as the oxidant under catalytic conditions epoxide was formed with modest yields and turnover numbers.

Tuning the reactivity of Fe(V)(O) toward C-H bonds at room temperature: effect of water.

The presence of an Fe(V)(O) species has been postulated as the active intermediate for the oxidation of both C-H and C═C bonds in the Rieske dioxygenase family of enzymes. Understanding the reactivity of these high valent iron-oxo intermediates, especially in an aqueous medium, would provide a better understanding of these enzymatic reaction mechanisms. The formation of an Fe(V)(O) complex at room temperature in an aqueous CH3CN mixture that contains up to 90% water using NaOCl as the oxidant is reported here. The stability of Fe(V)(O) decreases with increasing water concentration. We show that the reactivity of Fe(V)(O) toward the oxidation of C-H bonds, such as those in toluene, can be tuned by varying the amount of water in the H2O/CH3CN mixture. Rate acceleration of up to 60 times is observed for the oxidation of toluene upon increasing the water concentration. The role of water in accelerating the rate of the reaction has been studied using kinetic measurements, isotope labeling experiments, and density functional theory (DFT) calculations. A kinetic isotope effect of ∼13 was observed for the oxidation of toluene and d8-toluene showing that C-H abstraction was involved in the rate-determining step. Activation parameters determined for toluene oxidation in H2O/CH3CN mixtures on the basis of Eyring plots for the rate constants show a gain in enthalpy with a concomitant loss in entropy. This points to the formation of a more-ordered transition state involving water molecules. To further understand the role of water, we performed a careful DFT study, concentrating mostly on the rate-determining hydrogen abstraction step. The DFT-optimized structure of the starting Fe(V)(O) and the transition state indicates that the rate enhancement is due to the transition state's favored stabilization over the reactant due to enhanced hydrogen bonding with water.

Homogeneous photochemical water oxidation by biuret-modified Fe-TAML: evidence of Fe(V)(O) intermediate.

Water splitting, leading to hydrogen and oxygen in a process that mimics natural photosynthesis, is extremely important for devising a sustainable solar energy conversion system. Development of earth-abundant, transition metal-based catalysts that mimic the oxygen-evolving complex of photosystem II, which is involved in oxidation of water to O2 during natural photosynthesis, represents a major challenge. Further, understanding the exact mechanism, including elucidation of the role of active metal-oxo intermediates during water oxidation (WO), is critical to the development of more efficient catalysts. Herein, we report Fe(III) complexes of biuret-modified tetra-amidomacrocyclic ligands (Fe-TAML; 1a and 1b) that catalyze fast, homogeneous, photochemical WO to give O2, with moderate efficiency (maximum TON = 220, TOF = 0.76 s(-1)). Previous studies on photochemical WO using iron complexes resulted in demetalation of the iron complexes with concomitant formation of iron oxide nanoparticles (NPs) that were responsible for WO. Herein, we show for the first time that a high valent Fe(V)(O) intermediate species is photochemically generated as the active intermediate for the oxidation of water to O2. To the best of our knowledge, this represents the first example of a molecular iron complex catalyzing photochemical WO through a Fe(V)(O) intermediate.

Formation of a room temperature stable Fe(V)(O) complex: reactivity toward unactivated C-H bonds.

An Fe(V)(O) complex has been synthesized from equimolar solutions of (Et4N)2[Fe(III)(Cl)(biuret-amide)] and mCPBA in CH3CN at room temperature. The Fe(V)(O) complex has been characterized by UV-vis, EPR, Mössbauer, and HRMS and shown to be capable of oxidizing a series of alkanes having C-H bond dissociation energies ranging from 99.3 kcal mol(-1) (cyclohexane) to 84.5 kcal mol(-1) (cumene). Linearity in the Bell-Evans-Polayni graph and the finding of a large kinetic isotope effect suggest that hydrogen abstraction is engaged the rate-determining step.

Knowledge, attitude and skills before and after a module on pharmaceutical promotion in a Nepalese medical school.

BACKGROUND: Pharmaceutical promotion is widespread and can impact prescribing by health professionals. Little research has been conducted on interactions between medical students and the pharmaceutical industry. Teaching about pharmaceutical promotion is inadequate. A survey showed that many schools spend only about two hours teaching this important topic while others spend around six hours. Recently a manual on understanding and responding to promotion has been published by Health Action International (HAI) and the World Health Organization (WHO). From April to August 2011 the department of Clinical Pharmacology at KIST Medical College, Lalitpur, Nepal conducted a module on pharmaceutical promotion for second year students based on the manual. The module used active learning strategies such as brainstorming sessions, role plays and group activities. The study worked on the hypothesis that a module on pharmaceutical promotion will be effective in improving the knowledge, attitude and skills of medical students regarding pharmaceutical promotion. The impact of the module on knowledge, attitude and skills was tested using a retrospective-pre questionnaire. The scores according to gender and method of financing of medical education before and after the module were compared using appropriate non-parametric tests. RESULTS: Eighty-seven of the 100 second year students (87%) participated in the study. 47 were females (54%) and 39 (44.83%) were males and one did not state the gender. Seventy-seven students (88.5%) were self-financing while 9 were scholarship students. The median knowledge, attitude and skills score before the module were 9, 13 and 6 respectively while the overall score was 28. The scores increased significantly to 16, 15 and 14 respectively after the module while the overall score increased to 45. The median attitude scores and total scores were significantly higher among females both before and after the module. The scores did not vary with method of financing of medical education. All scores increased significantly at the end of the module. CONCLUSIONS: The nine hour module held over a period of four months was effective in improving respondents' knowledge, attitudes and skills about pharmaceutical promotion. The module was not resource intensive and used resources already available in the institution. Similar modules can be considered in other medical and health profession schools in Nepal, South Asia and other developing countries.

Student feedback about the use of literature excerpts in Sparshanam, a Medical Humanities module.

Medical humanities (MH) modules have been conducted for first year students at KIST Medical College, Lalitpur, Nepal for the last four years. Literature excerpts are widely used in MH programs in developed nations. In Nepal English language literature excerpts had been used previously in two modules. Problems noted were difficulty in comprehending the excerpts and relating them to the Nepalese scenario. The MH module for the 2011 intake was conducted from December 2011 to March 2012. The present study was conducted in the third week of March to obtain student perceptions about use of literature excerpts and suggestions for further improvement using a questionnaire. Literature excerpts used in the module dealt with Nepal and health-related topics. Sixty-eight of the 80 students (85%) participated in the study. The majority were male, self-financing and from urban areas. Respondents felt the excerpts introduced them to different aspects of the medical profession, prepared them for future practice, and underscored the importance of understanding the patients' feelings. The literature excerpts with which they could identify the most and the least were noted. There were no differences in median enjoyment and effectiveness scores of the literature excerpts according to subgroups of respondents. The suggested benefits of using literature in medical education were similar to those reported previously. Most respondents were able to appreciate the English language excerpts. They felt that Nepali language excerpts and those by Nepali writers could also be included. The findings would be of interest to educators in other developing nations introducing MH modules.

Student feedback about the use of role plays in Sparshanam, a medical humanities module.

BACKGROUND: At KIST Medical College, Lalitpur, Nepal, a Medical Humanities module for first year medical students has been conducted. Role plays are used to explore social, medical and sexual issues in the Nepalese context. The present study obtained student feedback about the role plays used in the module, the difficulties faced, and obtained suggestions for further improvement. METHOD: The module was conducted from January to August 2011 using a total of 15 role plays. Student feedback was obtained using a semi-structured questionnaire. Informal discussions were held and a questionnaire was circulated among the first year students who had participated in the module. RESULTS: Ninety-eight of the 100 students in the module participated in the study. The overall opinion regarding the role plays was positive. Students stated role plays helped to make module objectives concrete and interesting, made students identify with the problem being investigated and improved communication skills. Role plays were designed to address important health issues in Nepal and prepare students for addressing these issues in future practice. A lack of sufficient time for preparing the role plays and initial problems with group dynamics were mentioned by the respondents during the study. CONCLUSIONS: Student feedback about the use of role plays during the module was positive. Role plays helped in making module objectives more concrete and interesting, improved communication skills and addressed important health issues in Nepal. Role plays are not resource intensive and can be considered for use in medical schools in developing nations.

Student feedback about The Skeptic Doctor, a module on pharmaceutical promotion.

Pharmaceutical promotion is an integral part of modern medical practice. Surveys show that medical students have a positive attitude towards promotion. Pharmaceutical promotion is not adequately taught in medical schools. A module based on the manual produced by Health Action International was conducted for second year medical students at KIST Medical College, Lalitpur, Nepal. Student feedback on various aspects of the module was obtained using a semi-structured questionnaire. Eighty-six of the 100 students (86%) provided feedback about the module. Forty-five (52.3%) were female and 39 (45.3%) were male. Participant feedback about the module was positive. Small group work and role plays were appreciated, and the ratings of the module and the manual were satisfactory. Respondents felt pharmaceutical promotion will play an important role in their future practice and that the module prepared them to respond appropriately to promotion and select and use medicines properly. The module further developed on issues covered during pharmacology practical and majority felt the module was of relevance to Nepal. Students appreciated the module though there were suggestions for improvement. The module should be considered during the years of clinical training (third and fourth years) and internship and in other medical schools.

Feedback on and knowledge, attitude, and skills at the end of pharmacology practical sessions.

Concern has been raised about inadequate pharmacology teaching in medical schools and the high incidence of prescribing errors by doctors in training. Modifications in pharmacology teaching have been carried out in many countries. The present study was carried out using a semi-structured questionnaire to obtain students' perceptions of their knowledge, attitudes, and skills with regard to different subject areas related to rational prescribing at the end of two-year activity-based pharmacology practical learning sessions in a private medical school in Nepal. The effectiveness of the sessions and strengths and suggestions to further improve the sessions were also obtained. The median total knowledge, attitude, skills and overall scores were calculated and compared among different subgroups of respondents. The median effectiveness score was also calculated. Eighty of the 100 students participated; 37 were male and 43 female. The median knowledge, attitude, and skills scores were 24, 39, and 23, respectively (maximum scores being 27, 45, and 36). The median total score was 86 (maximum score being 108). The effectiveness score for most subject areas was 3 (maximum 4). The strengths were the activity-based nature of the session, use of videos and role-plays, and repeated practice. Students wanted more sessions and practice in certain areas. They also wanted more resources and an internet connection in the practical room. The skills scores were relatively low. The immediate impact of the sessions was positive. Studies may be needed to assess the long term impact. Similar programs should be considered in other medical schools in Nepal and other developing countries.