Objective To summarize the available conceptual models for factors contributing to medication adherence based on the World Health Organization (WHO)’s five dimensions of medication adherence via a systematic review, identify the patient groups described in available conceptual models, and present an adaptable conceptual model that describes the factors contributing to medication adherence in the identified patient groups. Methods We searched PubMed®, Embase®, CINAHL®, and PsycINFO® for English language articles published from inception until 31 March 2020. Full-text original publications in English that presented theoretical or conceptual models for factors contributing to medication adherence were included. Studies that presented statistical models were excluded. Two authors independently extracted the data. Results We identified 102 conceptual models, and classified the factors contributing to medication adherence using the WHO’s five dimensions of medication adherence, namely patient-related, medication-related, condition-related, healthcare system/healthcare provider-related, and socioeconomic factors. Eight patient groups were identified based on age and disease condition. The most universally addressed factors were patient-related factors. Medication-related, condition-related, healthcare system-related, and socioeconomic factors were represented to various extents depending on the patient group. By systematically examining how the WHO’s five dimensions of medication adherence were applied differently across the eight different patient groups, we present a conceptual model that can be adapted to summarize the common factors contributing to medication adherence in different patient groups. Conclusion Our conceptual models can be utilized as a guide for clinicians and researchers in identifying the facilitators and barriers to medication adherence and developing future interventions to improve medication adherence. Protocol Registration PROSPERO Identifier: CRD42020181316

Density functional theory calculations were used to investigate the three possible modes of activation for the coupling of CO with alkynyl indoles in the presence of a guanidine base. The first of these mechanisms, involving electrophilic activation, was originally proposed by Skrydstrup et al. (Angew. Chem. Int. Ed. 2015, 54, 6682). The second mechanism involves the nucleophilic activation of CO . Both of these electrophilic and nucleophilic activation processes involve the formation of a guanidine-CO zwitterion adduct. We have proposed a third mechanism involving the bifunctional activation of the bicyclic guanidine catalyst, allowing for the simultaneous activation of the indole and CO by the catalyst. We demonstrated that a second molecule of catalyst is required to facilitate the final cyclization step. Based on the calculated turnover frequencies, our newly proposed bifunctional activation mechanism is the most plausible pathway for this reaction under these experimental conditions. Furthermore, we have shown that this bifunctional mode of activation is consistent with the experimental results. Thus, this guanidine-catalyzed reaction favors a specific-base catalyzed mechanism rather than the CO activation mechanism. We therefore believe that this bifunctional mechanism for the activation of bicyclic guanidine is typical of most CO coupling reactions.