Unrevealing the Nitrogen Elusive Chirality of 3-Sulfanyl and 3-Sulfinyl N-Tosyl Isoindolinones by ECD Spectra: An Experimental and Theoretical Investigation.

The nitrogen-hybridization/pyramidalization of two solvated N-tosylisoindolinone derivatives having chiral residues in adjacent (I) or adjacent and distal (II) position has been investigated by a theoretical-computational procedure based on Molecular Dynamics simulations and Quantum-Chemical calculations. After validation of our methodology in providing a reliable repertory of conformations by modeling the electronic circular dichroism (EDC) spectra, the electronic features associated with N-pyramidalization were further characterized through Natural Bond Order (NBO) analysis. Comparing against the N-geometry observed in crystal structures as a reference, our findings reveal that the presence of neighbouring chiral centers induces a more pronounced N-pyramidalization in solution than in the solid state, both in I and II. Furthermore, NBO analysis confirms that the N-lactam mostly retains the sp2 character but exhibits slight configurational distortion (ξI=13°; ξII=21°), which significantly influences the chiroptical activities observed in ECD spectra of I and II. This substantiates the N-lactams as configurationally stable chiral centers.

Asymmetric Organocatalytic Mannich Reaction in the Synthesis of Hybrid Isoindolinone-Pyrazole and Isoindolinone-Aminal from Functionalized α-Amidosulfone.

The investigation of the reactivity of an α-amido sulfone derived from 2-formyl benzoate under organocatalytic conditions in the presence of acetylacetone allowed the synthesis of a new heterocyclic hybrid isoindolinone-pyrazole with high enantiomeric excess. Dibenzylamine was also used as a nucleophile to afford an isoindolinone with aminal substituent in 3-position in suitable selectivity. The use of Takemoto's bifunctional organocatalyst not only led to observed enantioselectivity but was also important in accomplishing the cyclization step in both cases. Notably, this catalytic system proved to be particularly effective in comparison to widely used phase transfer catalysts.

Theoretical-Computational Modeling of CD Spectra of Aqueous Monosaccharides by Means of Molecular Dynamics Simulations and Perturbed Matrix Method.

The electronic circular dichroism (ECD) spectra of aqueous d-glucose and d-galactose were modeled using a theoretical-computational approach combining molecular dynamics (MD) simulations and perturbed matrix method (PMM) calculations, hereafter termed MD-PMM. The experimental spectra were reproduced with a satisfactory accuracy, confirming the good performances of MD-PMM in modeling different spectral features in complex atomic-molecular systems, as already reported in previous studies. The underlying strategy of the method was to perform a preliminary long timescale MD simulation of the chromophore followed by the extraction of the relevant conformations through essential dynamics analysis. On this (limited) number of relevant conformations, the ECD spectrum was calculated via the PMM approach. This study showed that MD-PMM was able to reproduce the essential features of the ECD spectrum (i.e., the position, the intensity, and the shape of the bands) of d-glucose and d-galactose while avoiding the rather computationally expensive aspects, which were demonstrated to be important for the final outcome, such as (i) the use of a large number of chromophore conformations; (ii) the inclusion of quantum vibronic coupling; and (iii) the inclusion of explicit solvent molecules interacting with the chromophore atoms within the chromophore itself (e.g., via hydrogen bonds).

Synthesis of Nitrogen-Containing Heterocyclic Scaffolds through Sequential Reactions of Aminoalkynes with Carbonyls.

Sequential reactions of aminoalkynes represent a powerful tool to easily assembly biologically important polyfunctionalized nitrogen heterocyclic scaffolds. Metal catalysis often plays a key role in terms of selectivity, efficiency, atom economy, and green chemistry of these sequential approaches. This review examines the existing literature on the applications of reactions of aminoalkynes with carbonyls, which are emerging for their synthetic potential. Aspects concerning the features of the starting reagents, the catalytic systems, alternative reaction conditions, pathways and possible intermediates are provided.

Asymmetric Cascade Aza-Henry/Lactamization Reaction in the Highly Enantioselective Organocatalytic Synthesis of 3-(Nitromethyl)isoindolin-1-ones from α-Amido Sulfones.

The asymmetric synthesis of novel 3-substituted isoindolinones is herein reported. A new cascade reaction was developed that consisted of the asymmetric nitro-Mannich reaction of suitable α-amido sulfones designed from 2-formyl benzoates, followed by the in situ cyclization of the adducts. Very high enantioselectivities, up to 98% ee, and very good yields were obtained in the presence of the readily available neutral bifunctional organocatalyst derived from trans-1,2-diaminocyclohexane, which is known as Takemoto's catalyst. The investigation of the reactivity of the obtained products allowed either the selective Boc-deprotection or reduction of the nitro group, leading to further functionalized 3-substituted isoindolinones without affecting the enantiomeric purity.

Using qualitative, community-based input to steer post-coronavirus disease 2019 pharmacy practice in substance use.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has had a disproportionately negative impact on individuals with a substance use disorder (SUD). A rapidly changing public health and treatment environment has resulted in increased needs for pharmacist engagement in SUD-focused patient care. OBJECTIVES: This study used semistructured interviews of SUD professionals to evaluate where they believe pharmacy practice could better support people at risk of or having SUD in light of challenges posed by the COVID-19 pandemic. METHODS: Professionals dedicated to the care of individuals with SUD were recruited from a large community substance use coalition to participate in a qualitative study examining how pharmacists could take a more active role in SUD prevention, intervention, recovery, and harm reduction (HR). A consensual qualitative research approach was used in data analysis. RESULTS: Domains identified in analysis included pharmacists as educators of patients and communities, pharmacists as educators of health care providers, pharmacists as advocates for individuals with SUD, the need for increased pharmacist engagement owing to COVID-19 challenges for individuals with SUD, the need for expanded pharmacy practice interventions, and the need for pharmacist self-development. CONCLUSION: Increased medication counseling, HR practices, addressing stigma, and community-level education focused on SUD were among the most commonly reported areas for pharmacy practice development. In addition, the urgent need to adjust pharmacy practice in response to the COVID-19 pandemic was also identified by interviewees.

Electrochemical-Induced Cascade Reaction of 2-Formyl Benzonitrile with Anilines: Synthesis of N-Aryl Isoindolinones.

An electrochemical initiated tandem reaction of anilines with 2-formyl benzonitrile has been developed. Thus, unprecedented 3-N-aryl substituted isoindolinones have been conveniently achieved by constant current electrolysis in a divided cell using catalytic amount of electricity and supporting electrolyte and a Pt-cathode as working electrode. The origin of the electrochemical activation as well as the mechanism of the subsequent chemical cascade reactions have been investigated by DFT calculations.

The First Highly Enantioselective Synthesis of 3-Sulfinyl-Substituted Isoindolinones Having Adjacent Carbon and Sulfur Stereocenters.

A highly stereoselective access to 3-sulfinyl-substituted isoindolinones has been achieved by a tandem organocatalytic addition/cyclization reaction of 2-carbobenzyloxy-N-tosylbenzylidenimine with thiols and succeeding diastereoselective oxidation with MCPBA. First, enantioenriched isoindolinone N,S-acetals have been obtained through a dynamic kinetic asymmetric transformation induced by a bifunctional chiral thiourea organocatalyst. In turn, the newly created carbon stereocenter enabled a high diastereocontrol in the subsequent sulfoxidation. Based on DFT calculations, a theoretical rationale for the stereoselectivity of the oxidation reaction is also provided.

Beneficial opioid management strategies: A review of the evidence for the use of opioid treatment agreements.

Background: The Centers for Disease Control and Prevention (CDC) and American Society of Interventional Pain Physicians (ASIPP) guidelines recommend opioid treatment agreements to reduce the misuse and abuse of opioids, but evidence of their effectiveness has not been well-established. This controversy has led to their varied use in primary care settings. The purpose of this review is to collect studies that assess the value of opioid treatment agreements and associated opioid misuse outcomes in patients with chronic non-cancer pain. Methods: This study used a modified preferred reporting items for systematic reviews and meta-analyses (PRISMA) approach which is organized by five distinct elements or steps: beginning with a clearly formulated question, using the question to develop clear inclusion criteria to identify relevant studies, using an approach to appraise the studies or a subset of the studies, summarizing the evidence using an explicit methodology, and interpreting the findings of the review. Results: Of 283 articles identified, six eligible studies were evaluated and assessed for quality. The study design, setting, and participants varied across the studies evaluated, and the methods of measuring primary and secondary outcomes were also diverse across all studies. One study was a randomized clinical trial (RCT), four studies were retrospective cohort studies (RCS), and one study was a prospective cohort study (PCS). The design, methods, and indication for misuse of these studies contributed to quality scores of very low for one study, low for four studies, and moderate for one study. Conclusion: This systematic review shows weak evidence to support the effectiveness of patient prescriber agreements in the reduction and mitigation of opioid misuse and abuse. Further research is needed to determine if these agreements are beneficial as an opioid management strategy.

Assessing pharmacy student experience with, knowledge of and attitudes towards harm reduction: illuminating barriers to pharmacist-led harm reduction.

BACKGROUND: As the burden from the opioid epidemic continues to increase in the state of Minnesota and across the nation, the University of Minnesota College of Pharmacy seeks to design an innovative, comprehensive harm reduction curriculum in order to better train student pharmacists to serve the varied needs of the greater community. This study examines incoming individuals' baseline knowledge of and attitudes toward harm reduction in order to better inform curriculum planning and to ultimately produce pharmacists capable of impacting the devastating effects of the opioid crisis. METHODS: Incoming first-year pharmacy students took a survey focused on their knowledge of opioid overdose and the drug naloxone and also provided written reflections on their perceptions of harm reduction. Data was coded using consensual qualitative research (CQR) into appropriate domains. RESULTS: Pharmacy students beginning their professional education revealed a lack of knowledge of proper response to an overdose situation, with 18.56% unfamiliar with the opioid antagonist drug naloxone. Close to 10% (9.58%) of students expressed unwillingness to do anything other than call an ambulance during an overdose event, while 8.98% were either unsure or felt that they would not feel compelled to do something to help. Qualitative coding revealed many barriers to students' becoming capable harm reductionists, including lack of knowledge of substance use, addiction, and harm reduction, in addition to the presence of bias and stigma. CONCLUSION: In order to interrupt the cycle of misinformation and stigma within the larger community and the subgroup of medical providers, gaps in student knowledge must be addressed in meaningful, specific ways over the course of their pharmacy education. Evaluating baseline knowledge and beliefs informs the design of a flexible, action-oriented curriculum to produce well-trained pharmacists ready to engage in finding solutions to the opioid crisis.

Medication management in Minnesota schools: The need for school nurse-pharmacist partnerships.

BACKGROUND: Pharmacist participation in school medication management (MM) is minimal. School nurses are responsible for increasingly complex medication administration and management in schools. OBJECTIVES: The purpose of this study was to 1) assess the MM needs of school nurses in Minnesota, and 2) determine if and how interprofessional partnerships between nurses and pharmacists might optimize MM for students. METHODS: Researchers from the University of Minnesota College of Pharmacy, School Nurse Organization of Minnesota, and Minnesota Department of Health conducted a 32-item online survey of school nurses. RESULTS: Nurses administered the majority of medications at their school (69.9%) compared with unlicensed assistive personnel (29%). Stimulants (37.7%), asthma medications (25.7%), over-the-counter analgesics (17.8%), and insulin (6.6%) were the most commonly administered drug therapies. A clear majority of school nurses were interested in partnering with pharmacists: 90.3% thought that a pharmacist could assist with MM, 80% would consult with a pharmacist, and 12.3% reported that they already have informal access to a pharmacist. Topics that nurses would discuss with a pharmacist included new medications (71.6%), drug-drug interactions (67.1%), proper administration (52%), and storage (39.4%). The top MM concerns included 1) availability of students' medications and required documentation, 2) health literacy, 3) pharmacist consultations, 4) lack of time available for nurses to follow up with and evaluate students, 5) family-centered care, 6) delegation, 7) communication, and 8) professional development. CONCLUSION: Although the majority of school nurses surveyed indicated that partnerships with pharmacists would improve school MM, few had a formal relationship. Interprofessional partnerships focused on MM and education are high on the list of services that school nurses would request of a consultant pharmacist. Study results suggest that there are opportunities for pharmacists to collaborate with school nurses; further study is necessary to advance high-quality MM for students in Minnesota schools.

OPIOIDS: cultivating interprofessional collaboration to find solutions to public health problems.

This study evaluated perceived effectiveness of an interprofessional case-based activity that allowed medical and pharmacy students to engage in problem-solving around the role of social determinants of health (SDOH) in opioid misuse. Students participated in a case-based activity, and then completed a post-activity survey that included five open-ended questions and the Interprofessional Collaborative Competency Attainment Survey. Twelve pharmacy students (100%) and 47 medical students (75%) completed the post-activity survey. Results indicate the activity resulted in a statistically significant increase in student ability to: 1) recognize interprofessional team members' knowledge, skills, and contributions to the interprofessional team; 2) communicate effectively across professions; and 3) learn with, from, and about interprofessional team members to develop a patient care plan. Students also reported enhanced understanding of treatment considerations with opioid misuse, the role of SDOH, and recognition of the value of interprofessional collaboration in their future practice. This interprofessional case-based activity appeared to promote collaboration among students from different professional programs as they engaged in problem-solving around a contemporary public health issue that intersects their future practices. This activity may serve as a model for health professional programs, practitioners, healthcare systems, and communities that seek interprofessional solutions to combat opioid misuse.

Rates and consequences of posttraumatic distress among American Indian adults with type 2 diabetes.

This study examined the prevalence of screened posttraumatic stress disorder (PTSD) and associated diabetes-related outcomes. A sample of American Indian adults with type 2 diabetes (n = 218) participated in interviewer-administered surveys. Using a cutoff of 3 on the Primary Care PTSD screener, 21.8 % of participants screened positive for PTSD. PTSD symptoms were negatively associated with self-rated health status and positively associated with past year hospitalization after controlling for several demographic factors, but not after controlling for depressive symptoms. Past month frequency of hyperglycemia symptoms was not related to PTSD symptoms. When grouped by mental health conditions (neither screened PTSD nor depressive symptoms, screened PTSD only, depressive symptoms only, and both), those with both screened PTSD and depressive symptoms reported the highest proportion of any past month hyperglycemia, past year hospitalization, and low self-rated health status. Screened PTSD, especially in those with comorbid depressive symptoms, is an important consideration in diabetes care.

Strategies and steps fostering the success of medication management services in community pharmacies.

OBJECTIVES: To identify and describe the steps and strategies that community pharmacies with established medication management services have used to integrate medication management services into their practice settings. DESIGN: Qualitative case study with semistructured interviews and focus groups. SETTING: Community pharmacy organizations in Minnesota. PARTICIPANTS: Pharmacists and pharmacy leadership from 4 different pharmacy organizations including independent, chain, and health system pharmacies. INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Qualitative case study analysis of community pharmacy management and pharmacists' perceptions of the factors that led to the establishment and sustainability of their medication management programs. RESULTS: Focus groups and interviews were undertaken with 25 pharmacists and pharmacy leaders from 4 distinct community pharmacy organizations from April to June 2015. Five themes emerged, representing specific implementation and continuation stages of medication management services in community practice: Deciding to Act, Setting the Stage, Executing the Service, Sticking to It, and Continuing to Grow. CONCLUSION: This study sheds light on key stages that have commonly occurred across community pharmacies that are delivering medication management services. The results of this work may serve as a road map for other community pharmacies looking to integrate medication management services into their own practice settings.

Pilot study of patient perception of pharmacists as care providers based on health screening encounters with student pharmacists.

OBJECTIVES: To assess how patient perceptions of the clinical role of pharmacists may be affected by use of the AIDET communication tool during student-led health fairs, as well as how such events can help promote pharmacy practice. SETTING: 12 community health fair screenings throughout northeastern Minnesota and northwestern Wisconsin, from February to November 2012. PRACTICE DESCRIPTION: University of Minnesota-College of Pharmacy students trained in the use of AIDET employed the tool's techniques in their communication with health fair patient attendees. Project participants were those patients aged 18 years and older who successfully completed a health fair survey. PRACTICE INNOVATION: The AIDET communication tool is designed to provide consistency in patient encounters through the use of key words at key times. AIDET is a mnemonic acronym that stands for acknowledge, introduce, duration, explanation, and thank you. University of Minnesota-College of Pharmacy students are taught how to use the AIDET framework in classroom and laboratory settings prior to their interactions with patients at area health fairs. INTERVENTION: Health fair attendees were asked to complete a survey to determine their satisfaction level with student pharmacist-delivered pharmacy services. EVALUATION: 87 patients were surveyed, with a response rate of 22.5% and a completion rate of 91.6%. The average age of the patient population for the study cohort was 52 years, with greater than 50% being 65 years or older. Patient ages ranged from 24 to 89 years. RESULTS: When AIDET techniques were employed in a health fair setting, patients reported high levels of satisfaction with pharmacy services and said they felt "happy, comfortable, and trusting." CONCLUSION: The AIDET framework provides a consistent process for patient-centered care delivery because it places emphasis on patient needs and expectations. Use of the technique is capable of enhancing student and pharmacist engagement with patients.

Isoindolinones as Michael Donors under Phase Transfer Catalysis: Enantioselective Synthesis of Phthalimidines Containing a Tetrasubstituted Carbon Stereocenter.

Readily available chiral ammonium salts derived from cinchona alkaloids have proven to be effective phase transfer catalysts in the asymmetric Michael reaction of 3-substituted isoindolinones. This protocol provides a convenient method for the construction of valuable asymmetric 3,3-disubstituted isoindolinones in high yields and  moderate to good enantioselectivity. Diastereoselectivity was also investigated in the construction of contiguous tertiary and quaternary stereocenters. The use of acrolein as Michael acceptor led to an interesting tricyclic derivative, a pyrroloisoindolinone analogue, via a tandem conjugated addition/cyclization reaction.

Bifunctional phase-transfer catalysis in the asymmetric synthesis of biologically active isoindolinones.

New bifunctional chiral ammonium salts were investigated in an asymmetric cascade synthesis of a key building block for a variety of biologically relevant isoindolinones. With this chiral compound in hand, the development of further transformations allowed for the synthesis of diverse derivatives of high pharmaceutical value, such as the Belliotti (S)-PD172938 and arylated analogues with hypnotic sedative activity, obtained in good overall total yield (50%) and high enantiomeric purity (95% ee). The synthetic routes developed herein are particularly convenient in comparison with the current methods available in literature and are particularly promising for large scale applications.

Combined electrochemical/chemical methods for the synthesis and the molecular diversifying of isoindolinone-based heterocyclic scaffolds.

By means of C-H acids activation on Pt-cathode, an electrochemically initiated strategy aimed to developing a diversity-oriented synthesis based on the isoindolinone nucleus has been established. Conveniently, the achievement of a small library of new heterocycle-fused isoindolinone compounds with potential interest for drug design was carried out by using tandem reactions and one-pot sequential processes.

Point-of-care screenings at the University of Minnesota: mechanism for civic engagement.

OBJECTIVES To describe Wellness Initiative of the Northland (WIN) screening events; present participant results from those events; discuss the benefits of pharmacist-conducted, community-based point-of-care (POC) testing to medically underserved patients and to the profession of pharmacy; and describe logistical considerations in launching disease screening services. SETTING Pharmacist-led community health fairs in a variety of settings, including shopping malls, churches, community pharmacies, senior residence facilities, critical-access hospitals, and clinics. PRACTICE DESCRIPTION Disease screenings for economically disadvantaged residents of northeastern Minnesota and northwest Wisconsin, held between 2005 and 2012, through WIN. PRACTICE INNOVATION Mobile POC screenings for dyslipidemia, diabetes, hypertension, and osteoporosis. MAIN OUTCOME MEASURE Percentage of screenings with out-of-range readings. RESULTS Since 2005, WIN screenings have served more than 2,000 individuals, providing 4,152 POC screenings. Out-of-range readings were obtained for 40.3% of fingerstick cholesterol tests, 24.8% of fingerstick blood glucose tests, 24.3% of blood pressure tests, and 38.7% of quantitative ultrasound heel bone density readings. CONCLUSION Community-conducted POC testing functions both as an important public health service and a mechanism by which pharmacists and student pharmacists can become involved in civic engagement.

Report of the 2023-2024 Strategic Engagement Standing Committee.

The American Association of Colleges of Pharmacy (AACP) has long emphasized the value of strategic engagement, recognizing that it is critical to the success of pharmacy education, contributing to the expansion of pharmacy and public health practice, the fulfillment of institutional missions, and the meeting of programmatic needs. The 2023-2024 Strategic Engagement Committee (SEC or the Committee) was charged with operationalizing Advocacy Champions, creating an Advocacy Resource Guide to support Advocacy Champions in their engagement with diverse public and private stakeholders, offering formal training to Advocacy Champions in the form of a new Connect Community and Webinar Series, and conducting focus groups at the 2024 Annual Meeting to determine strengths of the Advocacy Guide and opportunities to support Advocacy Champions further.