End of life decision making when home mechanical ventilation is used to sustain breathing in Motor Neurone Disease: patient and family perspectives.

BACKGROUND: Motor Neurone Disease (MND) leads to muscle weakening, affecting movement, speech, and breathing. Home mechanical ventilation, particularly non-invasive ventilation (NIV), is used to alleviate symptoms and support breathing in people living with MND. While home mechanical ventilation can alleviate symptoms and improve survival, it does not slow the progression of MND. This study addresses gaps in understanding end-of-life decision-making in those dependent on home mechanical ventilation, considering the perspectives of patients, family members, and bereaved families. METHODS: A UK-wide qualitative study using flexible interviews to explore the experiences of people living with MND (n = 16), their family members (n = 10), and bereaved family members (n = 36) about the use of home mechanical ventilation at the end of life. RESULTS: Some participants expressed a reluctance to discuss end-of-life decisions, often framed as a desire to "live for the day" due to the considerable uncertainty faced by those with MND. Participants who avoided end-of-life discussions often engaged in 'selective decision-making' related to personal planning, involving practical and emotional preparations. Many faced challenges in hypothesising about future decisions given the unpredictability of the disease, opting to make 'timely decisions' as and when needed. For those who became dependent on ventilation and did not want to discuss end of life, decisions were often 'defaulted' to others, especially once capacity was lost. 'Proactive decisions', including advance care planning and withdrawal of treatment, were found to empower some patients, providing a sense of control over the timing of their death. A significant proportion lacked a clear understanding of the dying process and available options. CONCLUSIONS: The study highlights the complexity and evolution of decision-making, often influenced by the dynamic and uncertain nature of MND. The study emphasises the need for a nuanced understanding of decision-making in the context of MND.

Long-Lived Charge Separation in Single Crystals of an Electron Donor Covalently Linked to Four Acceptor Molecules.

Crystalline donor-acceptor (D-A) systems serve as an excellent platform for studying CT exciton creation, migration, and dissociation into free charge carriers for solar energy conversion. Donor-acceptor cocrystals have been utilized to develop an understanding of CT exciton formation in ordered organic solids; however, the strong electronic coupling of the D and A units can sometimes limit charge separation lifetimes due to their close proximity. Covalent D-A systems that preorganize specific donor-acceptor structures can assist in engineering crystal morphologies that promote long-lived charge separation to overcome this limitation. Here we investigate photogenerated CT exciton formation in a single crystal of a 2,5,8,11-tetraphenylperylene (PerPh4) donor to which four identical naphthalene-(1,4:5,8)-bis(dicarboximide) (NDI) electron acceptors are covalently attached at the para positions of the PerPh4 phenyl groups to yield PerPh4-NDI4. X-ray crystallography shows that the four NDIs pack pairwise into two distinct motifs. Two NDI acceptors of one PerPh4-NDI4 are positioned over the PerPh4 donors of adjacent PerPh4-NDI4 molecules with the donor and acceptor π-systems having a large dihedral angle between them, while the other two NDIs of PerPh4-NDI4 form xylene-NDI van der Waals π-stacks with the corresponding NDIs in adjacent PerPh4-NDI4 molecules. Upon selective photoexcitation of PerPh4 in the single crystal, CT exciton formation occurs in <300 fs yielding electron-hole pairs that live for more than ∼16 µs. This demonstrates the effectiveness of covalently linked D-A systems for engineering single crystal structures that promote efficient and long-lived charge separation for solar energy conversion.

A Tag-Free Platform for Synthesis and Screening of Cyclic Peptide Libraries.

In the realm of high-throughput screening (HTS), macrocyclic peptide libraries traditionally necessitate decoding tags, essential for both library synthesis and identifying hit peptide sequences post-screening. Our innovation introduces a tag-free technology platform for synthesizing cyclic peptide libraries in solution and facilitates screening against biological targets to identify peptide binders through unconventional intramolecular CyClick and DeClick chemistries (CCDC) discovered through our research. This combination allows for the synthesis of diverse cyclic peptide libraries, the incorporation of various amino acids, and facile linearization and decoding of cyclic peptide binder sequences. Our sensitivity-enhancing derivatization method, utilized in tandem with nano LC-MS/MS, enables the sequencing of peptides even at exceedingly low picomolar concentrations. Employing our technology platform, we have successfully unearthed novel cyclic peptide binders against a monoclonal antibody and the first cyclic peptide binder of HIV capsid protein responsible for viral infections as validated by microscale thermal shift assays (TSA), biolayer interferometry (BLI) and functional assays.

Medial opening wedge high tibial osteotomy for the treatment of medial unicompartmental knee osteoarthritis: A state-of-the-art review.

Medial unicompartmental knee osteoarthritis is a common condition that is frequently associated with significant pain and dysfunction. Medial opening wedge high tibial osteotomy (MOWHTO) offers a unique opportunity to preserve the knee joint and potentially alter the course of the degenerative process. Recent advances in this field of surgery have enabled surgeons to perform a MOWHTO in a safe, reliable and reproducible manner. This state-of-the-art review highlights the most important advances in the field of MOWHTO. Key concepts related to patient selection, pre-operative planning, surgical accuracy and patient outcome are considered. The importance of an individualized approach is emphasized and its influence on the future direction of the procedure is discussed.

Oriented Triplet Excitons as Long-Lived Electron Spin Qutrits in a Molecular Donor-Acceptor Single Cocrystal.

The photogeneration of multiple unpaired electron spins within molecules is a promising route to applications in quantum information science because they can be initialized into well-defined, multilevel quantum states (S > 1/2) and reproducibly fabricated by chemical synthesis. However, coherent manipulation of these spin states is difficult to realize in typical molecular systems due to the lack of selective addressability and short coherence times of the spin transitions. Here, these challenges are addressed by using donor-acceptor single cocrystals composed of pyrene and naphthalene dianhydride to host spatially oriented triplet excitons, which exhibit promising photogenerated qutrit properties. Time-resolved electron paramagnetic resonance (TREPR) spectroscopy demonstrates that spatially orienting triplet excitons in a single crystal platform imparts narrow, well-resolved, tunable resonances in the triplet EPR spectrum, allowing selective addressability of the spin sublevel transitions. Pulse-EPR spectroscopy reveals that at temperatures above 30 K, spin decoherence of these triplet excitons is driven by exciton diffusion. However, coherence is limited by electronic spin dipolar coupling below 30 K, where T2 varies nonlinearly with the optical excitation density due to exciton annihilation. Overall, an optimized coherence time of T2 = 7.1 µs at 20 K is achieved. These results provide important insights into designing solid-state molecular excitonic materials with improved spin qutrit properties.

A pile of pipelines: An overview of the bioinformatics software for metabarcoding data analyses.

Environmental DNA (eDNA) metabarcoding has gained growing attention as a strategy for monitoring biodiversity in ecology. However, taxa identifications produced through metabarcoding require sophisticated processing of high-throughput sequencing data from taxonomically informative DNA barcodes. Various sets of universal and taxon-specific primers have been developed, extending the usability of metabarcoding across archaea, bacteria and eukaryotes. Accordingly, a multitude of metabarcoding data analysis tools and pipelines have also been developed. Often, several developed workflows are designed to process the same amplicon sequencing data, making it somewhat puzzling to choose one among the plethora of existing pipelines. However, each pipeline has its own specific philosophy, strengths and limitations, which should be considered depending on the aims of any specific study, as well as the bioinformatics expertise of the user. In this review, we outline the input data requirements, supported operating systems and particular attributes of thirty-two amplicon processing pipelines with the goal of helping users to select a pipeline for their metabarcoding projects.

Cell-permeable chameleonic peptides: Exploiting conformational dynamics in de novo cyclic peptide design.

Membrane-traversing peptides offer opportunities for targeting intracellular proteins and oral delivery. Despite progress in understanding the mechanisms underlying membrane traversal in natural cell-permeable peptides, there are still several challenges to designing membrane-traversing peptides with diverse shapes and sizes. Conformational flexibility appears to be a key determinant of membrane permeability of large macrocycles. We review recent developments in the design and validation of chameleonic cyclic peptides, which can switch between alternative conformations to enable improved permeability through cell membranes, while still maintaining reasonable solubility and exposed polar functional groups for target protein binding. Finally, we discuss the principles, strategies, and practical considerations for rational design, discovery, and validation of permeable chameleonic peptides.

Singlet Fission in Perylene Monoimide Single Crystals and Polycrystalline Films.

Singlet fission (SF) is a spin-allowed process in which a photogenerated singlet exciton down-converts into two triplet excitons. Perylene-3,4-dicarboximide (PMI) has singlet and triplet state energies of 2.4 and 1.1 eV, respectively; thus making SF slightly exoergic and providing triplet excitons that have sufficient energy to raise the efficiency of single-junction solar cells by reducing thermalization losses from hot excitons formed when absorbed photons have energies higher than the semiconductor bandgap. However, PMI SF in the solid state has not been studied previously. Here, we show that 2,5-diphenyl-N-(2-ethylhexyl)perylene-3,4-dicarboximide (dp-PMI) crystallizes into a slip-stacked intermolecular morphology favorable for SF. Transient absorption microscopy and spectroscopy show that dp-PMI SF occurs in ≤50 ps in both single crystals and polycrystalline thin films with a triplet yield of 150 ± 20%. Ultrafast SF in the solid state, the high triplet yield, and its photostability make dp-PMI an attractive candidate for SF-enhanced solar cells.

Understanding living with tracheostomy ventilation for motor neuron disease and the implications for quality of life: a qualitative study protocol.

INTRODUCTION: Home mechanical ventilation can be used to manage symptoms of breathlessness and sustain life for people living with motor neuron disease (plwMND). In the UK, less than 1% of plwMND use tracheostomy ventilation (TV). This contrasts with some other countries, where rates are much higher. Due to a lack of evidence about its feasibility, cost-effectiveness or outcomes, TV is not covered in the UK National Institute for Health and Care Excellence guidance. Most plwMND receiving TV in the UK do so as an unplanned crisis intervention, which can lead to a prolonged hospital stay while a complex care package is arranged. There is insufficient literature addressing the burdens and benefits of TV, how it should be initiated and delivered, and how future care choices for plwMND can be supported. The aim of this research is to provide new understandings of the experiences of plwMND using TV, and those of family members and healthcare professionals (HCPs) involved in their care. METHODS AND ANALYSIS: A UK-wide qualitative study with two workstreams: (1) Patient focused case studies (n=6) including plwMND, family members and HCPs to focus on experiences and tasks of daily living from multiple perspectives. (2) Interviews with plwMND (n=10), family members, including bereaved family members (n=10) and HCPs (n=20) on broader experiences and issues relating to use of TV, such as ethical considerations and decision making. ETHICS AND DISSEMINATION: Ethical approval has been granted by the Leicester South Research Ethics Committee (22/EM/0256). All participants will be asked to provide electronic, written and/or audio recorded informed consent. Study findings will be disseminated in peer-reviewed journals and conference presentations and used to develop new resources for teaching and public information.

Global wood anatomical perspective on the onset of the Late Antique Little Ice Age (LALIA) in the mid-6th century CE.

Linked to major volcanic eruptions around 536 and 540 CE, the onset of the Late Antique Little Ice Age has been described as the coldest period of the past two millennia. The exact timing and spatial extent of this exceptional cold phase are, however, still under debate because of the limited resolution and geographical distribution of the available proxy archives. Here, we use 106 wood anatomical thin sections from 23 forest sites and 20 tree species in both hemispheres to search for cell-level fingerprints of ephemeral summer cooling between 530 and 550 CE. After cross-dating and double-staining, we identified 89 Blue Rings (lack of cell wall lignification), nine Frost Rings (cell deformation and collapse), and 93 Light Rings (reduced cell wall thickening) in the Northern Hemisphere. Our network reveals evidence for the strongest temperature depression between mid-July and early-August 536 CE across North America and Eurasia, whereas more localised cold spells occurred in the summers of 532, 540-43, and 548 CE. The lack of anatomical signatures in the austral trees suggests limited incursion of stratospheric volcanic aerosol into the Southern Hemisphere extra-tropics, that any forcing was mitigated by atmosphere-ocean dynamical responses and/or concentrated outside the growing season, or a combination of factors. Our findings demonstrate the advantage of wood anatomical investigations over traditional dendrochronological measurements, provide a benchmark for Earth system models, support cross-disciplinary studies into the entanglements of climate and history, and question the relevance of global climate averages.

Perioperative management of patients with amyotrophic lateral sclerosis: A narrative review.

Amyotrophic lateral sclerosis, or motor neuron disease, is an uncommon progressive neurological disorder. Professionals working in the perioperative field may encounter patients with amyotrophic lateral sclerosis only rarely. The relevant published literature on amyotrophic lateral sclerosis is broad in scope, but a contemporary review focused on the perioperative period is absent. This structured narrative review seeks to provide a summary of the contemporary management of patients and then focuses on eliciting if there are perioperative management considerations specific to amyotrophic lateral sclerosis that can be optimised. A comprehensive structured narrative literature review, including grey literature searching, indicated worsening ventilatory failure is of prime concern but that patients may present with a broad range of neurological symptoms, and that cardiovascular and cognitive dysfunction specific to amyotrophic lateral sclerosis may exist and be occult. Exacerbation of neuromuscular weakness during the perioperative period is multifaceted and requires the application of a high standard of the core principles of surgical and anaesthetic management of neuromuscular disease. Standard perioperative approaches require rigorous attention and potential exists for significant alteration. There is a potential high risk of postoperative increased morbidity from neurological decline and mortality from pulmonary complications. A meticulous approach to planning preoperative assessment, shared decision-making, intraoperative and postoperative care is required.

Accurate de novo design of membrane-traversing macrocycles.

We use computational design coupled with experimental characterization to systematically investigate the design principles for macrocycle membrane permeability and oral bioavailability. We designed 184 6-12 residue macrocycles with a wide range of predicted structures containing noncanonical backbone modifications and experimentally determined structures of 35; 29 are very close to the computational models. With such control, we show that membrane permeability can be systematically achieved by ensuring all amide (NH) groups are engaged in internal hydrogen bonding interactions. 84 designs over the 6-12 residue size range cross membranes with an apparent permeability greater than 1 × 10-6 cm/s. Designs with exposed NH groups can be made membrane permeable through the design of an alternative isoenergetic fully hydrogen-bonded state favored in the lipid membrane. The ability to robustly design membrane-permeable and orally bioavailable peptides with high structural accuracy should contribute to the next generation of designed macrocycle therapeutics.

A reciprocal translocation involving Aspergillus nidulans snxAHrb1/Gbp2 and gyfA uncovers a new regulator of the G2-M transition and reveals a role in transcriptional repression for the setBSet2 histone H3-lysine-36 methyltransferase.

Aspergillus nidulans snxA, an ortholog of Saccharomyces cerevisiae Hrb1/Gbp2 messenger RNA shuttle proteins, is-in contrast to budding yeast-involved in cell cycle regulation, in which snxA1 and snxA2 mutations as well as a snxA deletion specifically suppress the heat sensitivity of mutations in regulators of the CDK1 mitotic induction pathway. snxA mutations are strongly cold sensitive, and at permissive temperature snxA mRNA and protein expression are strongly repressed. Initial attempts to identify the causative snxA mutations revealed no defects in the SNXA protein. Here, we show that snxA1/A2 mutations resulted from an identical chromosome I-II reciprocal translocation with breakpoints in the snxA first intron and the fourth exon of a GYF-domain gene, gyfA. Surprisingly, a gyfA deletion and a reconstructed gyfA translocation allele suppressed the heat sensitivity of CDK1 pathway mutants in a snxA+ background, demonstrating that 2 unrelated genes, snxA and gyfA, act through the CDK1-CyclinB axis to restrain the G2-M transition, and for the first time identifying a role in G2-M regulation for a GYF-domain protein. To better understand snxA1/A2-reduced expression, we generated suppressors of snxA cold sensitivity in 2 genes: (1) loss of the abundant nucleolar protein Nsr1/nucleolin bypassed the requirement for snxA and (2) loss of the Set2 histone H3 lysine36 (H3K36) methyltransferase or a nonmethylatable histone H3K36L mutant rescued hypomorphic snxA mutants by restoring full transcriptional proficiency, indicating that methylation of H3K36 acts normally to repress snxA transcription. These observations are in line with known Set2 functions in preventing excessive and cryptic transcription of active genes.

Disease-related population declines in bats demonstrate non-exchangeability in generalist predators.

The extent to which persisting species may fill the functional role of extirpated or declining species has profound implications for the structure of biological communities and ecosystem functioning. In North America, arthropodivorous bats are threatened on a continent-wide scale by the spread of white-nose syndrome (WNS), a disease caused by the fungus Pseudogymnoascus destructans. We tested whether bat species that display lower mortality from this disease can partially fill the functional role of other bat species experiencing population declines. Specifically, we performed high-throughput amplicon sequencing of guano from two generalist predators: the little brown bat (Myotis lucifugus) and big brown bat (Eptesicus fuscus). We then compared changes in prey consumption before versus after population declines related to WNS. Dietary niches contracted for both species after large and abrupt declines in little brown bats and smaller declines in big brown bats, but interspecific dietary overlap did not change. Furthermore, the incidence and taxonomic richness of agricultural pest taxa detected in diet samples decreased following bat population declines. Our results suggest that persisting generalist predators do not necessarily expand their dietary niches following population declines in other predators, providing further evidence that the functional roles of different generalist predators are ecologically distinct.

The population genetics of the causative agent of snake fungal disease indicate recent introductions to the USA.

Snake fungal disease (SFD; ophidiomycosis), caused by the pathogen Ophidiomyces ophiodiicola (Oo), has been documented in wild snakes in North America and Eurasia, and is considered an emerging disease in the eastern United States of America. However, a lack of historical disease data has made it challenging to determine whether Oo is a recent arrival to the USA or whether SFD emergence is due to other factors. Here, we examined the genomes of 82 Oo strains to determine the pathogen's history in the eastern USA. Oo strains from the USA formed a clade (Clade II) distinct from European strains (Clade I), and molecular dating indicated that these clades diverged too recently (approximately 2,000 years ago) for transcontinental dispersal of Oo to have occurred via natural snake movements across Beringia. A lack of nonrecombinant intermediates between clonal lineages in Clade II indicates that Oo has actually been introduced multiple times to North America from an unsampled source population, and molecular dating indicates that several of these introductions occurred within the last few hundred years. Molecular dating also indicated that the most common Clade II clonal lineages have expanded recently in the USA, with time of most recent common ancestor mean estimates ranging from 1985 to 2007 CE. The presence of Clade II in captive snakes worldwide demonstrates a potential mechanism of introduction and highlights that additional incursions are likely unless action is taken to reduce the risk of pathogen translocation and spillover into wild snake populations.

Tracheostomy ventilation in motor neurone disease: a snapshot of UK practice.

Introduction: Motor neurone disease (MND) is characterized by rapidly progressive motor neurone degeneration which leads to muscle wasting. Mortality and morbidity are due to respiratory muscle failure which may be offset by ventilation. The aim of this observational study was to quantify the number and characteristics of patients living with MND choosing tracheostomy ventilation (TV) in the UK. Methods: Long-term ventilation services in the UK were invited to undertake a retrospective 5-year audit of MND patients under their care between April 2013 and March 2018 who had TV. Patient characteristics, the time spent on ventilation, hospital length of stay, discharge destination, and survival data were collected. Results: Sixty-eight MND patients were initiated on TV over the 5-year period. Eighty-one percent of patients received TV in an emergency setting with more than a third of these undiagnosed at presentation. Patients choosing elective TV were more likely to be male (85%) have a bulbar presentation (54%) and an increased survival of 10 months over the observation period. The mean length of hospital stay post TV was 136 days. Two-thirds of patients were discharged to their own home. Conclusion: Very few patients living with MND in the UK are currently receiving TV. In those who choose TV, there may be a survival advantage to planning an elective procedure. Despite the long inpatient stay and high care costs involved a majority of patients survived and were discharged to their own home.

A global community-sourced assessment of the state of conservation technology.

Conservation technology holds the potential to vastly increase conservationists' ability to understand and address critical environmental challenges, but systemic constraints appear to hamper its development and adoption. Understanding of these constraints and opportunities for advancement remains limited. We conducted a global online survey of 248 conservation technology users and developers to identify perceptions of existing tools' current performance and potential impact, user and developer constraints, and key opportunities for growth. We also conducted focus groups with 45 leading experts to triangulate findings. The technologies with the highest perceived potential were machine learning and computer vision, eDNA and genomics, and networked sensors. A total of 95%, 94%, and 92% respondents, respectively, rated them as very helpful or game changers. The most pressing challenges affecting the field as a whole were competition for limited funding, duplication of efforts, and inadequate capacity building. A total of 76%, 67%, and 55% respondents, respectively, identified these as primary concerns. The key opportunities for growth identified in focus groups were increasing collaboration and information sharing, improving the interoperability of tools, and enhancing capacity for data analyses at scale. Some constraints appeared to disproportionately affect marginalized groups. Respondents in countries with developing economies were more likely to report being constrained by upfront costs, maintenance costs, and development funding (p = 0.048, odds ratio [OR] = 2.78; p = 0.005, OR = 4.23; p = 0.024, OR = 4.26), and female respondents were more likely to report being constrained by development funding and perceived technical skills (p = 0.027, OR = 3.98; p = 0.048, OR = 2.33). To our knowledge, this is the first attempt to formally capture the perspectives and needs of the global conservation technology community, providing foundational data that can serve as a benchmark to measure progress. We see tremendous potential for this community to further the vision they define, in which collaboration trumps competition; solutions are open, accessible, and interoperable; and user-friendly processing tools empower the rapid translation of data into conservation action. Article impact statement: Addressing financing, coordination, and capacity-building constraints is critical to the development and adoption of conservation technology.

La tecnología de conservación tiene el potencial para incrementar considerablemente la habilidad de los conservacionistas para entender y lidiar con los retos ambientales más importantes, pero las restricciones sistémicas parecen dificultar su desarrollo y adopción. La comprensión de estas restricciones y las oportunidades para el avance todavía son limitadas. Encuestamos en línea a 248 usuarios y programadores mundiales de tecnología de conservación para identificar las percepciones existentes del desempeño e impacto potencial de las herramientas actuales, restricciones para los usuarios y programadores y oportunidades clave para el crecimiento. También realizamos grupos de discusión con 45 expertos destacados para triangular los hallazgos. Las tecnologías con el potencial percibido más alto fueron el aprendizaje mecánico y la visión por computadora, la genómica y el eADN y los sensores en red. El 95%, 94% y 92% de los respondientes, respectivamente, clasificó estas tecnologías como muy útiles o como puntos de inflexión. Los retos más apremiantes que afectaron al área como conjunto fueron la competencia por el financiamiento limitado, la duplicación de esfuerzos y el desarrollo inadecuado de capacidades. El 76%, 67% y 55% de los respondientes, respectivamente, identificaron estos retos como de interés primario. Las oportunidades clave para el crecimiento que se identificaron en los grupos de diálogo fueron el incremento de la colaboración y la distribución de información, la mejoría de la operatividad entre herramientas y la potenciación de la capacidad de análisis de datos a escala. Algunas restricciones parecieron afectar desproporcionadamente a grupos marginalizados. Los respondientes de países con economías en desarrollo tuvieron mayor probabilidad de reportar la restricción por los costos iniciales, costos de mantenimiento y la financiación del desarrollo (p = 0.048, tasa de probabilidad [OR] = 2.78; p = 0.005, OR = 4.23; p = 0.024, OR = 4.26), y las mujeres respondientes tuvieron una mayor probabilidad de reportar restricciones por la financiación del desarrollo y habilidades técnicas percibidas (p = 0.027, OR = 3.98; p = 0.048, OR = 2.33). A nuestro entendimiento, este es el primero intento por capturar formalmente las perspectivas y necesidades de la comunidad mundial de la tecnología de conservación, proporcionando datos fundamentales que pueden servir como referencia para medir el progreso. Vemos un potencial tremendo para que esta comunidad amplíe la visión que definen, en la cual la colaboración se sobrepone a la competencia; las soluciones son abierta, accesibles e interoperativas; y las herramientas intuitivas de procesamiento capacitan la traducción veloz de datos a acciones de conservación.

Response to Comment on "A global environmental crisis 42,000 years ago".

Our study on the exact timing and the potential climatic, environmental, and evolutionary consequences of the Laschamps Geomagnetic Excursion has generated the hypothesis that geomagnetism represents an unrecognized driver in environmental and evolutionary change. It is important for this hypothesis to be tested with new data, and encouragingly, none of the studies presented by Picin et al. undermine our model.

Response to Comment on "A global environmental crisis 42,000 years ago".

Our paper about the impacts of the Laschamps Geomagnetic Excursion 42,000 years ago has provoked considerable scientific and public interest, particularly in the so-called Adams Event associated with the initial transition of the magnetic poles. Although we welcome the opportunity to discuss our new ideas, Hawks' assertions of misrepresentation are especially disappointing given his limited examination of the material.

Understanding the influence of geometric and electronic structure on the excited state dynamical and photoredox properties of perinone chromophores.

In this work, a series of eight similarly structured perinone chromophores were synthesized and photophysically characterized to elucidate the electronic and structural tunability of their excited state properties, including excited state redox potentials and fluorescence lifetimes/quantum yields. Despite their similar structure, these chromophores exhibited a broad range of visible absorption properties, quantum yields, and excited state lifetimes. In conjunction with static and time-resolved spectroscopies from the ultrafast to nanosecond time regimes, time-dependent computational modeling was used to correlate this behavior to the relationship between non-radiative decay and the energy-gap law. Additionally, the ground and excited state redox potentials were calculated and found to be tunable over a range of 1 V depending on the diamine or anhydride used in their synthesis (Ered* = 0.45-1.55 V; Eox* = -0.88 to -1.67 V), which is difficult to achieve with typical photoredox-active transition metal complexes. These diverse chromophores can be easily prepared, and with their range of photophysical tunability, will be valuable for future use in photofunctional applications.