Evaluation of online educational curriculum on HPV vaccination practices among adult primary care providers.

BACKGROUND: Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States. While HPV is a vaccine-preventable illness, vaccine utilization rates in the United States remain low, particularly among adults. METHODS: The objective of this study was to assess the impact of an online, asynchronous educational module on HPV vaccination for adult primary care providers. We designed and implemented the module for family medicine, internal medicine, medicine/pediatrics, and obstetrics/gynecology providers in a community practice network affiliated with a large academic health system. We evaluated the effect of the module on provider knowledge, attitudes, and self-reported behaviors with pre-, post-, and delayed post-tests, using Likert-scales for measurement. We summarized data with descriptive statistics and compared changes in individuals using paired t-tests. RESULTS: One hundred forty-four out of 223 providers completed the module (response rate of 65%). At baseline, internists had the lowest knowledge scores compared to other specialties (pre-test mean of 3.6, out of 5, SD 1.2). Internists were also the least likely to counsel patients on HPV vaccination (mean 1.6, SD 0.9). There was a statistically significant improvement in knowledge from pre-test to post-test (from mean of 3.8 to 4.6, out of 5, p < .001) across all specialties. There was also statistically significant improvement in mean confidence for all providers from pre-test to post-test to identify patients aged 19-26 (3.3 to 3.7, p < .001) and patients aged 27-45 (2.7 to 3.5, p < .001) who needed vaccination. There was a statistically significant improvement in likelihood to counsel eligible patients on the risks of HPV infection (mean 2.3 to 2.8, p-value 0.002). The delayed post-test demonstrated retention of improved knowledge, confidence, and self-reported behavior. CONCLUSIONS: This study demonstrated that an asynchronous online module was effective at improving confidence, knowledge, and self-reported behavior of adult primary care providers in recommending HPV immunization. Given the important role that healthcare providers play in vaccine uptake, this study suggests that an online educational intervention can be a powerful tool to encourage increased utilization and delivery of the HPV vaccine. Further efforts are needed to educate internists and providers who take care of the adult population on HPV vaccination.

High Value Care in Cancer Surveillance and Screening: Evaluating an e-Curriculum for Primary Care Providers.

BACKGROUND: With an expected shortage of oncologists, primary care providers (PCPs) may need to manage more cancer surveillance and screening, areas where educational resources for PCPs have been limited. The goal of this e-curriculum was for PCPs to learn surveillance and screening for several common cancers. METHODS: The e-curriculum covered breast and colorectal cancer surveillance and lung cancer screening with (1) a pre-test assessing knowledge, attitudes, practice patterns, and confidence; (2) case vignette-based teaching; and (3) an immediate post-test (with knowledge and confidence items identical to the pre-test) providing feedback. A delayed post-test was administered several months later. The curriculum and test items were developed by content experts and evaluated in a primary care group practice. RESULTS: Of 167 community PCPs, 152 completed the pre-test (91%), 145 completed the immediate post-test (87%), and 63 completed the delayed post-test (37%); 62 PCPs completed all three tests (37%). The median score on the pre-test was 43%, immediate post-test was 93%, and delayed post-test was 70%. For PCPs completing all three tests, the median scores were 50%, 90%, and 70%, respectively (p < 0.0001). The percentage of PCPs confident in their knowledge 4 to 6 months after module completion compared to the pre-test baseline was statistically significant for lung cancer screening but not for cancer surveillance. CONCLUSION: This curriculum provided concise, effective education for PCPs on 3 common cancers. Limitations include content breadth and lack of data reflecting physician ordering patterns. Curricular strengths include its accessibility, immediate feedback, and effectiveness, with a significant improvement in immediate and delayed post-test knowledge. Given a lack of increased confidence to provide cancer surveillance, PCPs should rely on electronic medical record tools and other resources to guide appropriate surveillance care.

The proportion and trend of human immunodeficiency virus infections associated with men who have sex with men from Chinese voluntary blood donors: a systematic review and meta-analysis.

BACKGROUND: Human immunodeficiency virus (HIV)-positive cases associated with men who have sex with men (MSM) have rapidly increased over the past years. The objective of this study is to comprehensively evaluate the proportions, changing trends, and geographical distribution of MSM-associated HIV cases from Chinese voluntary blood donors by systematically reviewing the available literature. STUDY DESIGN AND METHODS: Major English and Chinese research databases were searched for studies reporting study locations, study years, the number of HIV infections among blood donors, and the number of HIV-positive donations associated with MSM in China. The proportion estimates were calculated; subgroup analyses and test for time trend were performed using software of comprehensive meta-analysis. RESULTS: Thirty-four studies met eligibility criteria. The pooled proportion of HIV-positive donations associated with MSM from 2001 to 2012 was 36.5% (95% confidence interval, 29.6%-44.1%). The epidemic was found to be more severe in northeast and north China compared to south China (59.6%; 55.0% vs. 3.8%, respectively). The proportion showed a significantly increasing trend over the study period (10.3% in 2001-2005; 38.6% in 2006-2009; and 47.6% in 2010-2012; trend test chi-square = 16.42, p < 0.001). CONCLUSION: The relatively high proportion of MSM- associated HIV-positive donors is of concern. Efficient and effective measures focused on public education and improving knowledge of blood safety are needed to prevent this at-risk population from seeking HIV testing through blood donation. It is also imperative to expand the scope of postdonation nucleic acid testing to shorten the window period to improve blood supply safety in China.

Utilization of a primary care-based cancer survivorship clinic: patterns and patient characteristics.

PURPOSE: The Johns Hopkins Primary Care for Cancer Survivors (PCCS) Clinic was established in 2015 to improve care delivery for the growing cancer survivor population. We aim to describe areas of care addressed by PCCS and factors associated with clinic utilization. METHODS: We conducted a retrospective chart review of the first 301 patients' clinic visits. We used negative binomial regression models to identify factors associated with the rate of PCCS clinic visits overall and for cancer surveillance and treatment-related effects. RESULTS: There were 1702 clinic visits across 301 patients during the study period (77% female, median age 61). The most common areas of care addressed were chronic medical problems (80%), preventive health care (62%), cancer surveillance (59%), treatment-related effects (50%), and new/acute problems (46%). Multivariate analyses found that age > 60 years (IRR = 1.9, 95% CI = 1.2-3.0, p = 0.007) and higher number of comorbidities (IRR = 1.2, 95% CI = 1.1 - 1.2, p < 0.001) were associated with more overall PCCS visits, while female gender was associated with fewer visits (IRR = 0.6, CI = 0.4 - 0.8, p = 0.001). Gastrointestinal cancer type, shorter length of survivorship, male gender, and higher number of comorbidities were associated with a higher rate of visits addressing both surveillance and treatment-related effects (p < 0.05). CONCLUSIONS: The PCCS clinic addressed cancer and non-cancer related needs. Older patients and survivors with more comorbidities had significantly increased clinic utilization. IMPLICATIONS FOR CANCER SURVIVORS: As the cancer survivor population grows, increasing access to survivorship clinics based in primary care may help meet these patients' diverse oncologic and general health needs.

Reversible dioxygen binding and arene hydroxylation reactions: Kinetic and thermodynamic studies involving ligand electronic and structural variations.

Copper-dioxygen interactions are of intrinsic importance in a wide range of biological and industrial processes. Here, we present detailed kinetic/thermodynamic studies on the O(2)-binding and arene hydroxylation reactions of a series of xylyl-bridged binuclear copper(I) complexes, where the effects of ligand electronic and structural elements on these reactions are investigated. Ligand 4-pyridyl substituents influence the reversible formation of side-on bound µ-η(2):η(2)-peroxodicopper(II) complexes, with stronger donors leading to more rapid formation and greater thermodynamic stability of product complexes [Cu(II) (2)((R)XYL)(O(2) (2-))](2+). An interaction of the latter with the xylyl π-system is indicated. Subsequent peroxo electrophilic attack on the arene leads to C-H activation and oxygenation with hydroxylated products [Cu(II) (2)((R)XYLO(2-))((-)OH)](2+) being formed. A related unsymmetrical binucleating ligand was also employed. Its corresponding O(2)-adduct [Cu(II) (2)(UN)(O(2) (2-))](2+) is more stable, but primarily because the subsequent decay by hydroxylation is in a relative sense slower. The study emphasizes how ligand electronic effects can and do influence and tune copper(I)-dioxygen complex formation and subsequent reactivity.

Money Talks: Pilot Financial Wellness Programs to Promote Positive Financial Planning Behaviors Among Residents.

PROBLEM: Graduate medical education programs and national organizations are becoming more involved in promoting trainee financial wellness. Current literature reports residents have poor financial knowledge, high debt levels, low concern about their finances, and deficits in financial preparedness, but there has been little published on best practices for implementing financial wellness programs for residents or measuring meaningful outcomes of such programs. APPROACH: From June 2017 to 2019, the authors invited 277 internal medicine residents from the Stony Brook University Hospital, Montefiore Medical Center, and Johns Hopkins Bayview Medical Center residency programs to participate in financial wellness programs. Each institution held at least one 90-minute financial planning session; Stony Brook also had biannual financial wellness check-ins. Participants were invited to complete a presession, an immediate postsession, and a year-end survey to assess changes in financial planning behaviors. OUTCOMES: Survey response rates were 49% (135/277) for the presession survey, 47% (130/277) for the immediate postsession survey, and 22% (61/277) for the year-end survey. Ninety-six percent (125/130) found the sessions helpful and 98% (120/123) recommended continuing the program in the future. At year-end, the most frequent completed financial planning actions prompted by the session included saving emergency funds, creating a monthly budget, consolidating loans via the Public Service Loan Forgiveness program, contributing to retirement savings, and participating in an employer's retirement plan. Residents liked that some sessions were during intern orientation before the selection of retirement plans. Postgraduate year (PGY) 1 residents were more likely to complete positive financial planning actions and to agree or strongly agree that the session prompted them to take financial planning actions than PGY-2 and PGY-3 residents. NEXT STEPS: While financial wellness programs are well received by internal medicine residents, more robust evidence is needed on curricular delivery methods and program features that promote positive financial planning behaviors.

Photoaffinity isolation and identification of proteins in cancer cell extracts that bind to platinum-modified DNA.

The activity of the anticancer drug cisplatin is a consequence of its ability to bind DNA. Platinum adducts bend and unwind the DNA duplex, creating recognition sites for nuclear proteins. Following DNA damage recognition, the lesions will either be repaired, facilitating cell viability, or if repair is unsuccessful and the Pt adduct interrupts vital cellular functions, apoptosis will follow. With the use of the benzophenone-modified cisplatin analogue Pt-BP6, 25 bp DNA duplexes containing either a 1,2-d(G*pG*) intrastrand or a 1,3-d(G*pTpG*) intrastrand crosslink were synthesized, where the asterisks designate platinated nucleobases. Proteins having affinity for these platinated DNAs were photocrosslinked and identified in cervical, testicular, pancreatic and bone cancer-cell nuclear extracts. Proteins identified in this manner include the DNA repair factors RPA1, Ku70, Ku80, Msh2, DNA ligase III, PARP-1, and DNA-PKcs, as well as HMG-domain proteins HMGB1, HMGB2, HMGB3, and UBF1. The latter strongly associate with the 1,2-d(G*pG*) adduct and weakly or not at all with the 1,3-d(G*pTpG*) adduct. The nucleotide excision repair protein RPA1 was photocrosslinked only by the probe containing a 1,3-d(G*pTpG*) intrastrand crosslink. The affinity of PARP-1 for platinum-modified DNA was established using this type of probe for the first time. To ensure that the proteins were not photocrosslinked because of an affinity for DNA ends, a 90-base dumbbell probe modified with Pt-BP6 was investigated. Photocrosslinking experiments with this longer probe revealed the same proteins, as well as some additional proteins involved in chromatin remodeling, transcription, or repair. These findings reveal a more complete list of proteins involved in the early steps of the mechanism of action of the cisplatin and its close analogue carboplatin than previously was available.

Women's Health Curricula in Internal Medicine Residency Programs: A Scoping Review.

Background: Despite national efforts to expand women's health education, internal medicine (IM) residents remain unprepared to provide comprehensive care to women. The objectives of this scoping review are to provide an overview of published women's health curricula in IM residency programs and to identify potential areas for improvement. Materials and Methods: Studies were identified using PubMed, Embase, Cochrane Library, Scopus, Education Resources Information Center (ERIC), Web of Science, and MedEdPORTAL. Inclusion criteria included the following: (1) women's health as defined by the authors (2) description of a curriculum (3) designed for IM residents (4) based in North America, and (5) published between 1998 and 2018. Data abstracted included content, educational and assessment methods, and quality. Descriptive analysis was used to compare data. Results: Sixteen articles met the inclusion criteria. The most common women's health topics were intimate partner violence (31%) and menopause (31%). Twelve curricula (75%) were implemented in the outpatient setting. Of the teaching methods, didactics (69%) and in-clinic teaching (44%) were most commonly used. All studies that assessed attitudes, knowledge, and/or behavior showed an improvement post-intervention. No studies evaluated patient outcomes. Conclusion: To our knowledge, this is the first review summarizing published women's health curricula in IM residency. There were a limited number of published articles describing women's health curricula. Although content varied, the curricula were effective in improving attitudes, knowledge, and/or behavior with regard to women's health topics. We encourage IM residency programs to develop and disseminate women's health curricula to inform future improvements and advancements in women's health education.

Describing the Evidence Base for Accreditation in Undergraduate Medical Education Internationally: A Scoping Review.

PURPOSE: To summarize the state of evidence related to undergraduate medical education (UME) accreditation internationally, describe from whom and where the evidence has come, and identify opportunities for further investigation. METHOD: The authors searched Embase, ERIC, PubMed, and Scopus from inception through January 31, 2018, without language restrictions, to identify peer-reviewed articles on UME accreditation. Articles were classified as scholarship if all Glassick's criteria were met and as nonscholarship if not all were met. Author, accrediting agency, and study characteristics were analyzed. RESULTS: Database searching identified 1,379 nonduplicate citations, resulting in 203 unique, accessible articles for full-text review. Of these and with articles from hand searching added, 36 articles were classified as scholarship (30 as research) and 85 as nonscholarship. Of the 36 scholarship and 85 nonscholarship articles, respectively, 21 (58%) and 44 (52%) had an author from the United States or Canada, 8 (22%) and 11 (13%) had an author from a low- or middle-income country, and 16 (44%) and 43 (51%) had an author affiliated with a regulatory authority. Agencies from high-income countries were featured most often (scholarship: 28/60 [47%]; nonscholarship: 70/101 [69%]). Six (17%) scholarship articles reported receiving funding. All 30 research studies were cross-sectional or retrospective, 12 (40%) reported only analysis of accreditation documents, and 5 (17%) attempted to link accreditation with educational outcomes. CONCLUSIONS: Limited evidence exists to support current UME accreditation practices or guide accreditation system creation or enhancement. More research is required to optimize UME accreditation systems' value for students, programs, and society.

New metal complexes as potential therapeutics.

The many activities of metal ions in biology have stimulated the development of metal-based therapeutics. Cisplatin, as one of the leading metal-based drugs, is widely used in treatment of cancer, being especially effective against genitourinary tumors such as testicular. Significant side effects and drug resistance, however, have limited its clinical applications. Biological carriers conjugated to cisplatin analogs have improved specificity for tumor tissue, thereby reducing side effects and drug resistance. Platinum complexes with distinctively different DNA binding modes from that of cisplatin also exhibit promising pharmacological properties. Ruthenium and gold complexes with antitumor activity have also evolved. Other metal-based chemotherapeutic compounds have been investigated for potential medicinal applications, including superoxide dismutase mimics and metal-based NO donors/scavengers. These compounds have the potential to modulate the biological properties of superoxide anion and nitric oxide.

Increase of RT-related transmitted drug resistance in non-CRF01_AE among HIV type 1-infected men who have sex with men in the 7 cities of China.

OBJECTIVES: To elucidate new features in the prevalence of HIV-1 transmitted drug resistance (TDR) in men who have sex with men (MSM) in China. METHODS: A total of 441 HIV-1-positive subjects were recruited from high-risk MSM populations in 7 cities across China between 2012 and 2013. Nucleotide sequences of 1.1-kb pol-RT regions were amplified and sequenced from 367 of the 441 samples. Phylogenetic and genetic drug-resistant analyses were performed. RESULTS: The overall distribution of HIV-1 genotypes was as the following: CRF01_AE, 52.3%; CRF07_BC, 33.2%; 01/B recombinants, 6.0%; subtype B (United States-European), 3.8%; subtype B', 3.8%; and CRF08_BC, 0.8%. About 91.3% of the sequences clustered together. An overall 4.6% TDR rate was found. Reverse transcriptase (RT)-related TDR reached 2.7%. TDR of 2.2% was detected in protease region. Most of RT-related TDRs were detected in non-CRF01_AE subtypes (90.0%, 9/10), including T215A/S, K101E, K103N, V106M, and E138G. Most of the strains with TDRs (88.2%, 15/17) were presented in the clusters. TDR strains against non-nucleoside reverse transcriptase inhibitors in non-CRF01_AE subtypes also formed some subclusters (70.0%, 7/10). One CRF07_BC subject with K103N in Kunming had a very close genetic distance with one that received highly active antiretroviral therapy locally (bootstrap = 99%). Two CRF55_01B subjects carrying K103N in Changsha and Nanjing also had a very close genetic distance (bootstrap = 100%). CONCLUSIONS: RT-related TDR of non-CRF01_AE became the main TDR among MSM in China. There is an increasing trend and a potential transmission risk for the RT-related TDR among MSM throughout China. Some TDRs could have already been transmitted among different cities. Intervention efforts should be strengthened among MSM to prevent further transmission of HIV and the proliferation of the strains with TDR.

Sexual Risk Behaviors and HIV Infection among Men Who Have Sex with Men and Women in China: Evidence from a Systematic Review and Meta-Analysis.

OBJECTIVES: To understand the current risk of HIV infection and transmission and further elucidate the underlying risk factors among men who have sex with men and women (MSMW) in China. METHODS: Following PRISMA guidelines, we conducted a systematic review and meta-analysis of searching through Chinese and English available literature databases between January 2000 and June 2014 to identify articles. RESULTS: Thirty-six articles (including 19,730 MSMW and 53,536 MSMO) met the selection criteria and the aggregated results found that MSMW have significantly higher HIV prevalence than MSMO (6.6% versus 5.4%, OR = 1.27, 95% CI = 1.01-1.58). A higher proportion of MSMW had commercial male partners in the past 6 months (18.3% versus 12.2%, OR = 1.56, 95% CI = 1.01-2.42). Additionally, substance use in the past 6 months was significantly more frequent among MSMW than MSMO (alcohol use: 27.1% versus 13.1%, OR = 2.53, 95% CI = 2.14-2.99; illicit drug use: 5.3% versus 2.5%, OR = 2.09, 95% CI = 1.48-2.95). CONCLUSION: A higher proportion of commercial sex and substance use among MSMW may be a potentially indicative factor for significantly higher HIV prevalence compared to MSMO. Targeted interventions should aim at increasing the frequency of HIV/STIs screening and preventing high risk commercial sex and substance use among MSMW to decrease their HIV transmission to the general population.

Circumscribed choroidal hemangioma associated with choroidal neovascularization in a HIV-infected case: photodynamic therapy and intravitreous ranibizumab.

Circumscribed choroidal hemangioma (CCH) is rarely associated with choroidal neovascularization (CNV), especially in HIV-infected patients. And the therapy is still controversial. In this study, we discussed the mechanism, clinical feature and treatment of such lesions, based on multi-modality imaging evidences. Photodynamic therapy (PDT) might aggravate CNV as a side effect, and we concluded that intravitreal ranibizumab could be suggested as an effective therapy.

Recreational drug use among Chinese men who have sex with men: a risky combination with unprotected sex for acquiring HIV infection.

OBJECTIVE: To investigate the prevalence of recreational drug use and its relationship with HIV infection among Chinese MSM. METHODS: A cross-sectional study of 625 MSM was conducted in Shenyang, China. Questionnaires were administered to collect information on recreational drug use and sexual behaviors. Blood specimens were collected to test for HIV and syphilis antibodies. RESULTS: Nearly a quarter (23.2%, 145/625) of participants reported ever using recreational drugs, among which alkyl nitrites (poppers) was the most frequently used drug (19.2%), followed by methylmorphine phosphate (5.1%), methamphetamine (4.0%), and ketamine (0.8%). The overall prevalence of HIV and syphilis was 9.6% and 10.4%, respectively. Multivariate logistic analysis showed that recreational drug use was significantly correlated with age ≤ 25 year (adjusted odds ratio [aOR] = 1.6, 95% CI, 1.1-2.9), single marital status (aOR = 2.1, 95% CI, 1.2-3.6), and seeking male sexual partners mainly through Internet (aOR = 1.8, 95% CI, 1.8-2.8). Recreational drug use was independently associated with an increased risk of HIV infection (aOR = 3.5, 95% CI, 2.0-6.2). CONCLUSIONS: Our study suggests that recreational drug use is popular among Chinese MSM and is associated with significantly increased HIV infection risk. HIV prevention intervention programs should reduce both drug use and risky sexual behaviors in this population.

Substrate oxidation by copper-dioxygen adducts: mechanistic considerations.

A series of copper-dioxygen adducts [{Cu(II)(MePY2)(R)}(2)(O(2))](B(C(6)F(5))(4))(2) (1(R)()), systematically varying in their electronic properties via ligand pyridyl donor substituents (R = H, MeO, and Me(2)N), oxidize a variety of substrates with varying C-H or O-H bond dissociation enthalpies. Detailed mechanistic studies have been carried out, including investigation of 1(R)() thermodynamic redox properties, 1(R)() tetrahydrofuran (THF) and N,N'-dimethylaniline (DMA) oxidation kinetics (including analyses of substrate dicopper binding equilibria), and application of mechanistic probes (N-cyclopropyl-N-methylaniline (CMA) and (p-methoxyphenyl)-2,2-dimethylpropanol (MDP)), which can distinguish if proton-coupled electron-transfer (PCET) processes proceed through concerted electron-transfer proton-transfer (ETPT) or consecutive electron-transfer proton-transfer (ET/PT) pathways. The results are consistent with those of previous complementary studies; at low thermodynamic driving force for substrate oxidation, an ET/PT is operable, but once ET (i.e., substrate one-electron oxidation) becomes prohibitively uphill, the ETPT pathway occurs. Possible differences in coordination structures about 1(Me)()()2(N)()/1(MeO)() compared to those of 1(H)() are also used to rationalize some of the observations.

Identification of nuclear proteins that interact with platinum-modified DNA by photoaffinity labeling.

Interactions between cellular proteins and cisplatin-modified DNA are important in determining the anticancer activity of the drug. To develop a general approach for identifying proteins that mediate cellular responses to cisplatin, photoreactive cisplatin analogues having a tethered benzophenone moiety were prepared and used to form the major 1,2-intrastrand platinum-DNA cross-links. Upon irradiation of the platinated DNA dissolved in a HeLa nuclear extract, the appended photolabile benzophenone group generates a highly reactive species that binds irreversibly to cellular proteins that interact with the probe. Several DNA-protein cross-linked adducts were identified that may function in the cellular processing of cisplatin-DNA adducts. Of these, PARP-1 had not previously been demonstrated directly to contact Pt-DNA cross-links in human cells.

Distinguishing rate-limiting electron versus H-atom transfers in Cu2O2-mediated oxidative N-dealkylations: application of inter- versus intramolecular kinetic isotope effects.

Copper-dioxygen adducts are important biological oxidants. To gain a better understanding of the underlying chemistries of such species, we report on a series of Cu2II-O2 complexes, [{CuII(MePY2)R'}2(O2)](B(C6F5)4)2 (1R') (where (MePY2)R' is a 4-pyridyl substituted bis[2-(2-(4-R'-pyridyl)ethyl]methylamine; R' = H, MeO, Me2N; Zhang, C. X.; et al. J. Am. Chem. Soc. 2003, 125, 634-635), which readily oxidize exogenous substrates. In this study, we explore the mechanism by which 1R' facilitates the oxidative N-dealkylation of para-substituted N,N-dimethylanilines (R-DMA; R = MeO, Me, H, CN). In the case of 1H, the linear free-energy correlation plot (rho = -2.1) and intramolecular deuterium kinetic isotope effect (KIEintra, using p-R-(C6H4)-N(CH3)(CD3)) profile suggest that R-DMA oxidation occurs through rate-limiting electron transfer (ET). This mechanism was further enforced by comparison of KIEintra versus the intermolecular KIE (KIEinter, using p-R-(C6H4)-N(CH3)2 versus p-R-(C6H4)-N(CD3)2). It was found that KIEinter < KIEintra, suggesting an ET process. In the case of both 1MeO and 1Me2N, the KIEintra profile and linear free-energy correlation plots (rho = -0.49 and -0.99 for 1Me2N and 1MeO with especially poor fitting for the latter) are inconclusive in distinguishing between a rate-limiting ET or hydrogen atom transfer (HAT) pathway. Comparisons of KIEinter versus KIEintra demonstrate a switch in mechanism from ET to HAT for 1Me2N and 1MeO oxidation of R-DMA as R-DMA is made less reducing. In the case of 1Me2N, MeO-DMA and Me-DMA are oxidized via a rate-limiting ET (KIEinter < KIEintra), while H-DMA and CN-DMA are oxidized through a HAT pathway (KIEinter approximately KIEintra). For 1MeO, oxidation occurs through an ET pathway for MeO-, Me-, and H-DMA (KIEinter < KIEintra), while CN-DMA is oxidized though a HAT process (KIEinter approximately KIEintra). Copper complex attributes, which may contribute to the mechanistic observations, are suggested.

Resonance raman investigation of equatorial ligand donor effects on the Cu(2)O(2)(2+) core in end-on and side-on mu-peroxo-dicopper(II) and bis-mu-oxo-dicopper(III) complexes.

The effect of endogenous donor strength on Cu(2)O(2) bonds was studied by electronically perturbing [[(R-TMPA)Cu(II)]](2)(O(2))](2+) and [[(R-MePY2)Cu](2)(O(2))](2+) (R = H, MeO, Me(2)N), which form the end-on mu-1,2 bound peroxide and an equilibrium mixture of side-on peroxo-dicopper(II) and bis-mu-oxo-dicopper(III) isomers, respectively. For [[(R-TMPA)Cu(II)](2)(O(2))](2+), nu(O-O) shifts from 827 to 822 to 812 cm(-1) and nu(Cu)(-)(O(sym)) shifts from 561 to 557 to 551 cm(-1), respectively, as R- varies from H to MeO to Me(2)N. Thus, increasing the N-donor strength to the copper decreases peroxide pi(sigma) donation to the copper, weakening the Cu-O and O-O bonds. A decrease in nu(Cu-O) of the bis-mu-oxo-dicopper(III) complex was also observed with increasing N-donor strength for the R-MePY2 ligand system. However, no change was observed for nu(O-O) of the side-on peroxo. This is attributed to a reduced charge donation from the peroxide pi(sigma) orbital with increased N-donor strength, which increases the negative charge on the peroxide and adversely affects the back-bonding from the Cu to the peroxide sigma orbital. However, an increase in the bis-mu-oxo-dicopper(III) isomer relative to side-on peroxo-dicopper(II) species is observed for R-MePY2 with R = H < MeO < Me(2)N. This effect is attributed to the thermodynamic stabilization of the bis-mu-oxo-dicopper(III) isomer relative to the side-on peroxo-dicopper(II) isomer by strong donor ligands. Thus, the side-on peroxo-dicopper(II)/bis-mu-oxo-dicopper(III) equilibrium can be controlled by electronic as well as steric effects.

Copper(I)-dioxygen reactivity of [(L)Cu(I)](+) (L = tris(2-pyridylmethyl)amine): kinetic/thermodynamic and spectroscopic studies concerning the formation of Cu-O2 and Cu2-O2 adducts as a function of solvent medium and 4-pyridyl ligand substituent variations.

The kinetic and thermodynamic behavior of O(2)-binding to Cu(I) complexes can provide fundamental understanding of copper(I)/dioxygen chemistry, which is of interest in chemical and biological systems. Here we report stopped-flow kinetic investigations of the oxygenation reactions of a series of tetradentate copper(I) complexes [(L(R))Cu(I)(MeCN)](+) (1(R), R=H, Me, tBu, MeO, Me(2)N) in propionitrile (EtCN), tetrahydrofuran (THF), and acetone. The syntheses of 4-pyridyl substituted tris(2-pyridylmethyl)amine ligands (L(R)) and copper(I) complexes are detailed. Variations of ligand electronic properties are manifested in the electrochemistry of 1(R) and nu(CO) of [(L(R))Cu(I)-CO](+) complexes. The kinetic studies in EtCN and THF show that the O(2)-reactions of 1(R) follow the reaction mechanism established for oxygenation of 1(H) in EtCN (J. Am. Chem. Soc. 1993, 115, 9506), involving reversible formation (k(1)/k(-1)) of [(L(R))Cu(II)(O(2-))](+) (2(R)), which further reacts (k(2)/k(-2)) with 1(R) to form the 2:1 Cu(2)O(2) complex [[(L(R))Cu(II)](2)(O(2)(2-))](2+) (3(R)). In EtCN, the rate constants for formation of 2(R) (k(1)) are not dramatically affected by the ligand electronic variations. For R = Me and tBu, the kinetic and thermodynamic parameters are very similar to those of the parent complex (1(H)); e.g., k(1) is in the range 1.2 x 10(4) to 3.1 x 10(4) M(-1) s(-1) at 183 K. With the stronger donors R = MeO and Me(2)N, more significant effects were observed, with the expected increase in thermodynamic stability of resultant 2(R) and 3(R) complexes, and decreased dissociation rates. The modest ligand electronic effects manifested in EtCN are due to the competitive binding of solvent and dioxygen to the copper centers. In THF, a weakly coordinating solvent, the formation rate for 2(H) is much faster (>/=100 times) than that in EtCN, and the thermodynamic stabilities of both the 1:1 (K(1)) and 2:1 (beta = K(1)K(2)) copper-dioxygen species are much higher than those in EtCN (e.g., for 2(H), deltaH(o) (K(1))=-41 kJ mol(-1) in THF versus -29.8 kJ mol(-1) in EtCN; for 3(H), deltaH(o) (beta)=-94 kJ mol(-1) in THF versus -77 kJ mol(-1) in EtCN). In addition, a more significant ligand electronic effect is seen for the oxygenation reactions of 1(MeO) in THF compared to that in EtCN; the thermal stability of superoxo- and peroxocopper complexes are considerably enhanced using L(MeO) compared to L(H). In acetone as solvent, a different reaction mechanism involving dimeric copper(I) species [(L(R))(2)Cu(I)(2)](2+) is proposed for the oxygenation reactions, supported by kinetic analyses, electrical conductivity measurements, and variable-temperature NMR spectroscopic studies. The present study is the first systematic study investigating both solvent medium and ligand electronic effects in reactions forming copper-dioxygen adducts.