The impact of treatment for childhood classical Hodgkin lymphoma according to the EuroNet-PHL-C2 protocol on serum anti-Müllerian Hormone.

STUDY QUESTION: What is the impact of the EuroNet-PHL-C2 treatment protocol for children with classical Hodgkin lymphoma (cHL) on gonadal function in girls, based on assessment of serum anti-Müllerian hormone (AMH)? SUMMARY ANSWER: Serum AMH levels decreased after induction chemotherapy and increased during subsequent treatment and 2 years of follow-up, with lowest levels in patients treated for advanced stage cHL. WHAT IS KNOWN ALREADY: Treatment for cHL, particularly alkylating agents and pelvic irradiation, can be gonadotoxic and result in premature reduction of primordial follicles in females. The current EuroNet-PHL-C2 trial aims to reduce the use of radiotherapy in standard childhood cHL treatment, by intensifying chemotherapy. This study aims to assess the gonadotoxic effect of the EuroNet-PHL-C2 protocol. STUDY DESIGN, SIZE, DURATION: This international, prospective, multicenter cohort study is embedded in the EuroNet-PHL-C2 trial, an European phase-3 treatment study evaluating the efficacy of standard cHL treatment with OEPA-COPDAC-28 (OEPA: vincristine, etoposide, prednisone, and doxorubicin; COPDAC-28: cyclophosphamide, vincristine, prednisone, and dacarbazine) versus intensified OEPA-DECOPDAC-21 (DECOPDAC-21: COPDAC with additional doxorubicin and etoposide and 25% more cyclophosphamide) in a randomized setting. Participants were recruited between January 2017 and September 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: Female patients aged ≤18 years, treated according to the EuroNet-PHL-C2 protocol for cHL were recruited across 18 sites in the Netherlands, Belgium, Germany, Austria, and Czech Republic. All parents and patients (aged ≥12 years old) provided written informed consent. Serum AMH levels and menstrual cycle characteristics were evaluated over time (at diagnosis, one to three times during treatment and 2 up to 5 years post-diagnosis) and compared between treatment-levels (TL1, TL2, and TL3) and treatment-arms (OEPA-COPDAC-28 and OEPA-DECOPDAC-21). Serum samples obtained from patients after receiving pelvic radiotherapy were excluded from the main analyses. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 104 females, with median age at diagnosis of 15.6 years (IQR 13.7; 17.0), were included in the analysis. Ninety-nine were (post)pubertal. Eighteen girls were diagnosed with an early stage of cHL (TL1) and 86 with intermediate or advanced stage disease (50 TL2 and 36 TL3, 66% received COPDAC-28 and 34% DECOPDAC-21). Five patients received pelvic radiotherapy. Median AMH level at diagnosis was 1.7 µg/l (IQR 0.9; 2.7). After two courses of OEPA chemotherapy, AMH levels decreased substantially in all patients (98% <0.5 µg/l), followed by a significant increase during the consolidation treatment and follow-up. After 2 years, 68% of patients reached their baseline AMH value, with overall median recovery of 129% (IQR 75.0; 208.9) compared to baseline measurement. Five patients (7%) had AMH <0.5 µg/l. In patients treated for advanced stage disease, AMH levels remained significantly lower compared to early- or intermediate stage disease, with median serum AMH of 1.3 µg/l (IQR 0.8; 2.1) after 2 years. Patients who received DECOPDAC-21 consolidation had lower AMH levels during treatment than patients receiving COPDAC-28, but the difference was no longer statistically significant at 2 years post-diagnosis. Of the 35 postmenarchal girls who did not receive hormonal co-treatment, 19 (54%) experienced treatment-induced amenorrhea, two girls had persisting amenorrhea after 2 years. LIMITATIONS, REASONS FOR CAUTION: The studied population comprises young girls with diagnosis of cHL often concurring with pubertal transition, during which AMH levels naturally rise. There was no control population, while the interpretation of AMH as a biomarker during childhood is complex. The state of cHL disease may affect AMH levels at diagnosis, potentially complicating assessment of AMH recovery as a comparison with baseline AMH. The current analysis included data up to 2-5 years post-diagnosis. WIDER IMPLICATIONS OF THE FINDINGS: The current PANCARE guideline advises to use the cyclophosphamide-equivalent dose score (CED-score, as an estimation of cumulative alkylating agent exposure) with a cut-off of 6000 mg/m2 to identify females aged <25 years at high risk of infertility. All treatment-arms of the EuroNet-PHL-C2 protocol remain below this cut-off, and based on this guideline, girls treated for cHL should therefore be considered low-risk of infertility. However, although we observed an increase in AMH after chemotherapy, it should be noted that not all girls recovered to pre-treatment AMH levels, particularly those treated for advanced stages of cHL. It remains unclear how our measurements relate to age-specific expected AMH levels and patterns. Additional (long-term) data are needed to explore clinical reproductive outcomes of survivors treated according to the EuroNet-PHL-C2 protocol. STUDY FUNDING/COMPETING INTEREST(S): The fertility add-on study was funded by the Dutch charity foundation KiKa (project 257) that funds research on all forms of childhood cancer. C.M-K., D.K., W.H.W., D.H., M.C., A.U., and A.B. were involved in the development of the EuroNet-PHL-C2 regimen. The other authors indicated no potential conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Extended Reichardt's Dye-Synthesis and Solvatochromic Properties.

Three new pyridinium-phenolate dyes based on the benchmark solvatochromic dye Betaine 30 were synthesised. The dyes contained phenylene spacers between the donor and acceptor groups. Their UV-Vis absorption spectra were measured, with the dyes showing strong negative solvatochromic behaviour comparable to that of Betaine 30. These results stood in contrast to the behaviour of the π-extended dye Betaine 21, originally reported in 1963. This dye was synthesised and found to be significantly more solvatochromic than previously reported but prone to degrade. All π-extended dyes synthesised were found to be unstable in certain solvents. Although the increased distance between donor and acceptor did not enhance solvatochromism to the extent predicted, it was still determined that the reduced planarity caused by a phenylene spacer is not as detrimental as believed.

Protection of Boronic Acids Using a Tridentate Aminophenol ONO Ligand for Selective Suzuki-Miyaura Coupling.

Boronic acid protecting group chemistry powerfully enhances the versatility of Suzuki-Miyaura cross-coupling. Prominent examples include trifluoroborate salts, N-methyliminodiacetic acid (MIDA) boronates, and 1,8-diaminonaphthalene boronamides. In this work, we present a bis(2-hydroxybenzyl)methylamine (BOMA) ligand that forms tridentate complexes with boronic acids much like the MIDA ligand but the deprotection is facilitated by organic acids. The BOMA boronates showed considerable stability in both aqueous base and acid, and a variety of chemoselective reactions were performed on these boronates, including selective Suzuki-Miyaura coupling, palladium-catalyzed borylation, ester hydrolysis, alkylation, lithiation-borylation, and oxidative hydroxydeboronation.

Unusual Alternating Crystallization-Induced Emission Enhancement Behavior in Nonconjugated ω-Phenylalkyl Tropylium Salts.

The alternating physical properties, especially melting points, of α,ω-disubstituted n-alkanes and their parent n-alkanes had been known since Baeyer's report in 1877. There is, however, no general and comprehensive explanation for such a phenomenon. Herein, we report the synthesis and examination of a series of novel ω-phenyl n-alkyl tropylium tetrafluoroborates, which also display alternation in their physicochemical characters. Despite being organic salts, the compounds with odd numbers of carbons in the alkyl bridge exist as room temperature ionic liquids. In stark contrast to this, the analogues with even numbers of carbons in the linker are crystalline solids. These solid nonconjugated molecules exhibit curious photoluminescent properties, which can be attributed to their ability to form through-space charge-transfer complexes to cause crystallization-induced emission enhancement. Most notably, the compound with the highest photoluminescent quantum yield in this series showed an unusual arrangement of carbocationic dimer in the solid state. A combination of XRD analysis and ab initio calculations revealed interesting insights into these systems.

Triplet fusion upconversion using sterically protected 9,10-diphenylanthracene as the emitter.

Improving the efficiency of triplet fusion upconversion (TF-UC) in the solid-state is still challenging due to the aggregation and phase separation of chromophores. In this work, two 9,10-diphenylanthracene (DPA) derivatives based on the modification of the 9,10-phenyl rings with bulky isopropyl groups (bDPA-1 and bDPA-2) were used as emitters. By using platinum octaethylporphyrin (PtOEP) as the sensitizer, TF-UC performance was comprehensively investigated in 3 media: toluene solution, polyurethane thin film and nano/micro-crystals in a polyvinyl alcohol matrix. Only a small difference in upconversion efficiency between the bulky DPAs and the DPA reference was observed in toluene solution and polyurethane thin film. However, a large improvement of TF-UC quantum yield was achieved in bDPA-2/PtOEP crystals (ΦUC = (0.92 ± 0.05)%) with a low excitation intensity threshold (52 mW cm-2) compared to that of DPA/PtOEP crystals (ΦUC = (0.09 ± 0.03)%). This difference was largely attributed to improved dispersibility of the PtOEP sensitizer in the bDPA-2 emitter crystals. The bulky DPAs also show excellent stability under UV irradiation with exposure to oxygen compared to DPA. These results provide a strategy for developing efficient solid-state TF-UC systems based on nano/micro-particles of emitter-sensitizer mixtures.

Bilirubin analogues as model compounds for exciton coupling.

A series of phycobilin analogues have been investigated in terms of coupled excitonic systems. These compounds consist of a monomer, a tetrapyrrole structurally similar to bilirubin (bR), and two conjugated bR analogues. Spectroscopic and computational methods have been used to investigate the degree of interchromophore coupling. We find the synthesised bR analogue shows stronger excitonic coupling than bR, owing to a different molecular geometry. The excitonic coupling in the conjugated molecules can be controlled by modifying the bridge side-group. New computed energy levels for bR using the DFT/MRCI method are also presented, which improve on published values and re-assign the character of excited singlet states.

A Molecular Chameleon for Mapping Subcellular Polarity in an Unfolded Proteome Environment.

Environmental polarity is an important factor that drives biomolecular interactions to regulate cell function. Herein, a general method of using the fluorogenic probe NTPAN-MI is reported to quantify the subcellular polarity change in response to protein unfolding. NTPAN-MI fluorescence is selectively activated upon labeling unfolded proteins with exposed thiols, thereby reporting on the extent of proteostasis. NTPAN-MI also reveals the collapse of the host proteome caused by influenza A virus infection. The emission profile of NTPAN-MI contains information of the local polarity of the unfolded proteome, which can be resolved through spectral phasor analysis. Under stress conditions that disrupt different checkpoints of protein quality control, distinct patterns of dielectric constant distribution in the cytoplasm can be observed. However, in the nucleus, the unfolded proteome was found to experience a more hydrophilic environment across all the stress conditions, indicating the central role of nucleus in the stress response process.

Metaphase II oocytes from human unilaminar follicles grown in a multi-step culture system.

STUDY QUESTION: Can complete oocyte development be achieved from human ovarian tissue containing primordial/unilaminar follicles and grown in vitro in a multi-step culture to meiotic maturation demonstrated by the formation of polar bodies and a Metaphase II spindle? SUMMARY ANSWER: Development of human oocytes from primordial/unilaminar stages to resumption of meiosis (Metaphase II) and emission of a polar body was achieved within a serum free multi-step culture system. WHAT IS KNOWN ALREADY: Complete development of oocytes in vitro has been achieved in mouse, where in vitro grown (IVG) oocytes from primordial follicles have resulted in the production of live offspring. Human oocytes have been grown in vitro from the secondary/multi-laminar stage to obtain fully grown oocytes capable of meiotic maturation. However, there are no reports of a culture system supporting complete growth from the earliest stages of human follicle development through to Metaphase II. STUDY DESIGN, SIZE, DURATION: Ovarian cortical biopsies were obtained with informed consent from women undergoing elective caesarean section (mean age: 30.7 ± 1.7; range: 25-39 years, n = 10). PARTICIPANTS/MATERIALS, SETTING, METHODS: Laboratory setting. Ovarian biopsies were dissected into thin strips, and after removal of growing follicles were cultured in serum free medium for 8 days (Step 1). At the end of this period secondary/multi-laminar follicles were dissected from the strips and intact follicles 100-150 µm in diameter were selected for further culture. Isolated follicles were cultured individually in serum free medium in the presence of 100 ng/ml of human recombinant Activin A (Step 2). Individual follicles were monitored and after 8 days, cumulus oocyte complexes (COCs) were retrieved by gentle pressure on the cultured follicles. Complexes with complete cumulus and adherent mural granulosa cells were selected and cultured in the presence of Activin A and FSH on membranes for a further 4 days (Step 3). At the end of Step 3, complexes containing oocytes >100 µm diameter were selected for IVM in SAGE medium (Step 4) then fixed for analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Pieces of human ovarian cortex cultured in serum free medium for 8 days (Step 1) supported early follicle growth and 87 secondary follicles of diameter 120 ± 6 µm (mean ± SEM) could be dissected for further culture. After a further 8 days, 54 of the 87 follicles had reached the antral stage of development. COCs were retrieved by gentle pressure from the cultured follicles and those with adherent mural granulosa cells (n = 48) were selected and cultured for a further 4 days (Step 3). At the end of Step 3, 32 complexes contained oocytes >100 µm diameter were selected for IVM (Step 4). Nine of these complexes contained polar bodies within 24 h and all polar bodies were abnormally large. Confocal immuno-histochemical analysis showed the presence of a Metaphase II spindle confirming that these IVG oocytes had resumed meiosis but their developmental potential is unknown. LIMITATIONS, REASONS FOR CAUTION: This is a small number of samples but provides proof of concept that complete development of human oocytes can occur in vitro. Further optimization with morphological evaluation and fertilization potential of IVG oocytes is required to determine whether they are normal. WIDER IMPLICATIONS OF THE FINDINGS: The ability to develop human oocytes from the earliest follicular stages in vitro through to maturation and fertilization would benefit fertility preservation practice. STUDY FUNDING/COMPETING INTEREST(S): Funded by MRC Grants (G0901839 and MR/L00299X/1). No competing interests.

Emissive Molecular Aggregates and Energy Migration in Luminescent Solar Concentrators.

Luminescent solar concentrators (LSCs) are light harvesting devices that are ideally suited to light collection in the urban environment where direct sunlight is often not available. LSCs consist of highly luminescent compounds embedded or coated on a transparent substrate that absorb diffuse or direct solar radiation over a large area. The resulting luminescence is trapped in the waveguide by total internal reflection to the thin edges of the substrate where the concentrated light can be used to improve the performance of photovoltaic devices. The concept of LSCs has been around for several decades, and yet the efficiencies of current devices are still below expectations for commercial viability. There are two primary challenges when designing new chromophores for LSC applications. Reabsorption of dye emission by chromophores within the waveguide is a significant loss mechanism attenuating the light output of LSCs. Concentration quenching, particularly in organic dye systems, restricts the quantity of chromophores that can be incorporated in the waveguide thus limiting the light absorbed by the LSC. Frequently, a compromise between increased light harvesting of the incident light and decreasing emission quantum yield is required for most organic chromophore-based systems due to concentration quenching. The low Stokes shift of common organic dyes used in current LSCs also imposes another optimization problem. Increasing light absorption of LSCs based on organic dyes to achieve efficient light harvesting also enhances reabsorption. Ideally, a design strategy to simultaneously optimize light harvesting, concentration quenching, and reabsorption of LSC chromophores is clearly needed to address the significant losses in LSCs. Over the past few years, research in our group has targeted novel dye structures that address these primary challenges. There is a common perception that dye aggregates are to be avoided in LSCs. It became apparent in our studies that aggregates of chromophores exhibiting aggregation-induced emission (AIE) behavior are attractive candidates for LSC applications. Strategic application of AIE chromophores has led to the development of the first organic-based transparent solar concentrator that harvests UV light as well as the demonstration of reabsorption reduction by taking advantage of energy migration processes between chromophores. Further developments led us to the application of perylene diimides using an energy migration/energy transfer approach. To prevent concentration quenching, a molecularly insulated perylene diimide with bulky substituents attached to the imide positions was designed and synthesized. By combining the insulated perylene diimide with a commercial perylene dye as an energy donor-acceptor emitter pair, detrimental luminescence reabsorption was reduced while achieving a high chromophore concentration for efficient light absorption. This Account reviews and reinspects some of our recent work and the improvements in the field of LSCs.

Cancer risk in children born after donor ART.

STUDY QUESTION: Do children born after donor ART have an increased risk of developing childhood cancer in comparison to the general population? SUMMARY ANSWER: This study showed no overall increased risk of childhood cancer in individuals born after donor ART. WHAT IS KNOWN ALREADY: Most large population-based studies have shown no increase in overall childhood cancer incidence after non-donor ART; however, other studies have suggested small increased risks in specific cancer types, including haematological cancers. Cancer risk specifically in children born after donor ART has not been investigated to date. STUDY DESIGN, SIZE, DURATION: This retrospective cohort study utilized record linkage to determine the outcome status of all children born in Great Britain (1992-2008) after donor ART. The cohort included 12 137 members who contributed 95 389 person-years of follow-up (average follow-up 7.86 years). PARTICIPANTS/MATERIALS, SETTING, METHODS: Records of all children born in Great Britain (England, Wales, Scotland) after all forms of donor ART (1992-2008) were linked to the UK National Registry of Childhood Tumours (NRCT) to determine the number who subsequently developed cancer by 15 years of age, by the end of 2008. Rates of overall and type specific cancer (selected a priori) were compared with age, sex and calendar year standardized population-based rates, stratifying for potential mediating/moderating factors including sex, age at diagnosis, birth weight, multiple births, maternal previous live births, assisted conception type and fresh/ cryopreserved cycles. MAIN RESULTS AND THE ROLE OF CHANCE: In our cohort of 12 137 children born after donor ART (52% male, 55% singleton births), no overall increased risk of cancer was identified. There were 12 cancers detected compared to 14.4 expected (standardized incidence ratio (SIR) 0.83; 95% CI 0.43-1.45; P = 0.50). A small, significant increased risk of hepatoblastoma was found, but the numbers and absolute risks were small (<5 cases observed; SIR 10.28; 95% CI 1.25-37.14; P < 0.05). This increased hepatoblastoma risk was associated with low birthweight. LIMITATIONS REASONS FOR CAUTION: Although this study includes a large number of children born after donor ART, the rarity of specific diagnostic subgroups of childhood cancer results in few cases and therefore wide CIs for such outcomes. As this is an observational study, it is not possible to adjust for all potential confounders; we have instead used stratification to explore potential moderating and mediating factors, where data were available. WIDER IMPLICATIONS OF THE FINDINGS: This is the first study to investigate cancer risk in children born after donor ART. Although based on small numbers, results are reassuring for families and clinicians. The small but significant increased risk of hepatoblastoma detected was associated with low birthweight, a known risk factor for this tumour type. It should be emphasized that the absolute risks are very small. However, on-going investigation with a longer follow-up is needed. STUDY FUNDING/COMPETING INTEREST(S): This work was funded by Cancer Research UK (C36038/A12535) and the National Institute for Health Research (405526) and supported by the National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London. The work of the Childhood Cancer Research Group (CCRG) was supported by the charity CHILDREN with CANCER UK, the National Cancer Intelligence Network, the Scottish Government and the Department of Health for England and Wales. There are no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Exciton Dynamics of Photoexcited Pendant Porphyrin Polymers in Solution and in Thin Films.

Several new polymers with rotatable zinc porphyrin pendants have been synthesized and their optical spectroscopic and photophysical properties, including upconversion efficiencies, determined in both fluid solution and thin films. Comparisons made with the ß-substituted zinc tetraphenylporphyrin monomers and ZnTPP itself reveal that the yield of triplets resulting from either Q-band or Soret-band excitation of the polymers is surprisingly small. A detailed kinetic analysis of the fluorescence decays and transient triplet absorptions of the substituted monomers and their corresponding polymers reveals that this phenomenon is due to two parallel internal singlet quenching processes assigned to transient intrachain excimer formation. Consequently, the yields of upconverted S2 fluorescence resulting from Q-band excitation in the degassed polymers are significantly diminished in both fluid solution and thin films. Implications of these results for the design of polymer upconverting systems are discussed.

Non-growing follicle density is increased following adriamycin, bleomycin, vinblastine and dacarbazine (ABVD) chemotherapy in the adult human ovary.

STUDY QUESTION: Do the chemotherapeutic regimens of ABVD (adriamycin, bleomycin, vinblastine and dacarbazine) or OEPA-COPDAC (combined vincristine, etoposide, prednisone, doxorubicin (OEPA) and cyclophosphamide, vincristine, prednisone, dacarbazine (COPDAC)) used to treat Hodgkin lymphoma (HL), affect the density, morphology and in vitro developmental potential of human ovarian follicles? SUMMARY ANSWER: Ovarian tissue from women treated with ABVD contained a higher density of non-growing follicles (NGFs) per cubic millimetre and increased numbers of multiovular follicles but showed reduced in vitro growth compared with patients with lymphoma who had not received chemotherapy, patients treated with OEPA-COPDAC, age-matched healthy women and age-related model-predicted values. WHAT IS KNOWN ALREADY: Chemotherapy regimens can cause a loss of follicles within the ovary, which depends on the drugs given. Early stage HL is commonly treated by ABVD, a non-alkylating regimen that apparently has ovarian sparing qualities; thus it is important to investigate the histological appearance and distribution of follicles within ABVD-treated ovarian tissue. STUDY DESIGN, SIZE, DURATION: Thirteen ovarian biopsies were obtained from HL patients (six adolescents and seven adults) and one biopsy from a non-HL patient. Two HL patients and the non-HL patient had received no treatment prior to biopsy collection. The remaining 11 HL patients received one of two regimens: ABVD or OEPA-COPDAC. Tissue was analysed histologically and compared to biopsies from healthy women, and in a subgroup of patients, tissue was cultured for 6 days in vitro. PARTICIPANTS/MATERIALS, SETTING, METHODS: Ovarian biopsies were obtained from patients undergoing ovarian cryopreservation for fertility preservation and from healthy women at the time of Caesarian section ('obstetric tissue'). Follicle number and maturity were evaluated in sections of ovarian cortical tissue, and compared to an age-related model of mean follicle density and to age-matched contemporaneous biopsies. The developmental potential of follicles was investigated after 6 days of tissue culture. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 6877 follicles were analysed. ABVD-treated tissue contained a higher density of NGFs per cubic millimetre (230 ± 17) (mean ± SEM) than untreated (110 ± 54), OEPA-COPDAC-treated (50 ± 27) and obstetric (20 ± 4) tissue (P < 0.01), with follicle density 9-21 SD higher than predicted by an age-related model. Biovular and binucleated NGFs occurred frequently in ABVD-treated and in adolescent-untreated tissue but were not observed in OEPA-COPDAC-treated or obstetric tissue, although OEPA-COPDAC-treated tissue contained a high proportion of morphologically abnormal oocytes (52% versus 23% in untreated, 22% in ABVD-treated and 25% in obstetric tissue; P < 0.001). Activation of follicle growth in vitro occurred in all groups, but in ABVD-treated samples there was very limited development to the secondary stage, whereas in untreated samples from lymphoma patients growth was similar to that observed in obstetric tissue (untreated; P < 0.01 versus ABVD-treated, NS versus obstetric). LARGE SCALE DATA: N/A LIMITATIONS, REASONS FOR CAUTION: Although a large number of follicles were analysed, these data were derived from a small number of biopsies. The mechanisms underpinning these observations have yet to be determined and it is unclear how they relate to future fertility. WIDER IMPLICATIONS OF THE FINDINGS: This study confirms that the number of NGFs is not depleted following ABVD treatment, consistent with clinical data that female fertility is preserved. Our findings demonstrate that immature follicle density can increase as well as decrease following at least one chemotherapy treatment. This is the first report of morphological and follicle developmental similarities between ABVD-treated tissue and the immature human ovary. Further experiments will investigate the basis for the marked increase in follicle density in ABVD-treated tissue. STUDY FUNDING/COMPETING INTERESTS: Funded by UK Medical Research Council Grants G0901839 and MR/L00299X/1. The authors have no competing interests.

Determinants of the efficiency of photon upconversion by triplet-triplet annihilation in the solid state: zinc porphyrin derivatives in PVA.

Spectroscopic, photophysical and computational studies designed to expose and explain the differences in the efficiencies of non-coherent photon upconversion (NCPU) by triplet-triplet annihilation (TTA) have been carried out for a new series of alkyl-substituted diphenyl and tetraphenyl zinc porphyrins, both in fluid solution and in solid films. Systematic variations in the alkyl-substitution of the phenyl groups in both the di- and tetraphenyl porphyrins introduces small, but well-understood changes in their spectroscopic and photophysical properties and in their TTA efficiencies. In degassed toluene solution TTA occurs for all derivatives and produces the fluorescent S2 product states in all cases. In PVA matrices, however, none of the di-phenylporphyrins exhibit measurable NCPU whereas all the tetraphenyl-substituted compounds remain upconversion-active. In PVA the NCPU efficiencies of the zinc tetraphenylporphyrins vary significantly with their steric characteristics; the most sterically crowded tetraphenyl derivative exhibits the greatest efficiency. DFT-D computations have been undertaken and help reveal the sources of these differences.

Highly Fluorescent Pyridinium Betaines for Light Harvesting.

We report the findings of our experimental and theoretical investigations into the properties of pyridinium enolates and their potential utility in light-harvesting applications, such as in luminescent solar concentrators (LSCs). We present the synthesis, structures, photophysical characterization, and wavefunction-based quantum-chemical studies of five cyclobetaines. The performance of an LSC device incorporating one of these cyclobetaines is shown to be comparable to state-of-the-art devices.

A Green Route to Conjugated Polyelectrolyte Interlayers for High-Performance Solar Cells.

Synthesis of fluorene-based conjugated polyelectrolytes was achieved via Suzuki polycondensation in water and completely open to air. The polyelectrolytes were conveniently purified by dialysis and analysis of the materials showed properties expected for fluorene-based conjugated polyelectrolytes. The materials were then employed in solar cell devices as an interlayer in conjunction with ZnO. The double interlayer led to enhanced power conversion efficiency of 10.75 % and 15.1 % for polymer and perovskite solar cells, respectively.

Re-implantation of cryopreserved ovarian cortex resulting in restoration of ovarian function, natural conception and successful pregnancy after haematopoietic stem cell transplantation for Wilms tumour.

With the improvement of long-term cancer survival rates, growing numbers of female survivors are suffering from treatment-related premature ovarian insufficiency (POI). Although pre-treatment embryo and oocyte storage are effective fertility preservation strategies, they are not possible for pre-pubertal girls or women who cannot delay treatment. In these cases, the only available treatment option is ovarian cortex cryopreservation and subsequent re-implantation. A 32-year-old woman had ovarian cortex cryopreserved 10 years previously before commencing high-dose chemotherapy and undergoing a haematopoietic stem cell transplant for recurrent adult Wilms tumour, which resulted in POI. She underwent laparoscopic orthotopic transplantation of cryopreserved ovarian cortex to the original site of biopsy on the left ovary. She ovulated at 15 and 29 weeks post-re-implantation with AMH detectable, then rising, from 21 weeks, and conceived naturally following the second ovulation. The pregnancy was uncomplicated and a healthy male infant was born by elective Caesarean section at 36+4 weeks gestation. This is the first report of ovarian cortex re-implantation in the UK. Despite the patient receiving low-risk chemotherapy prior to cryopreservation and the prolonged tissue storage duration, the re-implantation resulted in rapid restoration of ovarian function and natural conception with successful pregnancy.

High performance p-type molecular electron donors for OPV applications via alkylthiophene catenation chromophore extension.

The synthesis of key 4-alkyl-substituted 5-(trimethylsilyl)thiophene-2-boronic acid pinacol esters 3 allowed a simplified alkylthiophene catenation process to access bis-, ter-, quater-, and quinquethiophene π-bridges for the synthesis of acceptor-π-bridge-donor- π-bridge-acceptor (A-π-D-π-A) electron donor molecules. Based on the known benzodithiophene-terthiophene-rhodanine (BTR) material, the BXR series of materials, BMR (X = M, monothiophene), BBR (X = B, bithiophene), known BTR (X = T, terthiophene), BQR (X = Q, quaterthiophene), and BPR (X = P(penta), quinquethiophene) were synthesised to examine the influence of chromophore extension on the device performance and stability for OPV applications. The BTxR (x = 4, butyl, and x = 8, octyl) series of materials were synthesised by varying the oligothiophene π-bridge alkyl substituent to examine structure-property relationships in OPV device performance. The devices assembled using electron donors with an extended chromophore (BQR and BPR) are shown to be more thermally stable than the BTR containing devices, with un-optimized efficiencies up to 9.0% PCE. BQR has been incorporated as a secondary donor in ternary blend devices with PTB7-Th resulting in high-performance OPV devices with up to 10.7% PCE.

Organic Photovoltaic Materials--Design, Synthesis and Scale-Up.

This account describes the work of our group in the area of organic photovoltaics in the past six years. The emphasis is on our experiences in the development of the organic materials, their characterization, scale-up and application in devices. We share our insight into the relationship between synthetic methods, molecular properties, bulk material properties and device performance.

Regioselective synthesis of fullerene multiadducts via tether-directed 1,3-dipolar cycloaddition.

The regioselective synthesis of fullerene multiadducts was achieved from commercially available reagents in one pot over two steps. The configuration of the isolated regioisomers was determined using various NMR methods, UV-vis spectroscopy and electrochemical analysis with the structure of one isomer confirmed by single crystal X-ray analysis. Interesting variation in regioselectivity was observed when different amino acid reagents were used in the reactions. Theoretical calculations and additional experiments, such as deuterium exchange, led to a proposed mechanism for the regioselective product formation.

An externally validated age-related model of mean follicle density in the cortex of the human ovary.

PURPOSE: The ability to accurately estimate a woman's ovarian reserve by non-invasive means is the goal of ovarian reserve prediction. It is not known whether a correlation exists between model-predicted estimates of ovarian reserve and data generated by direct histological analysis of ovarian tissue. The aim of this study was to compare mean non-growing follicle density values obtained from analysis of ovarian cortical tissue samples against ovarian volume models. METHODS: Non-growing follicle density values were obtained from 13 ovarian cortical biopsies (16-37 years). A mean non-growing follicle density was calculated for each patient by counting all follicles in a given volume of biopsied ovarian cortex. These values were compared to age-matched model generated densities (adjusted to take into consideration the proportion of ovary that is cortex) and the correlation between data sets tested. RESULTS: Non-growing density values obtained from fresh biopsied ovarian cortical samples closely matched model generated data with low mean difference, tight agreement limits and no proportional error between the observed and predicted results. CONCLUSION: These findings validate the use of the adjusted population and ovarian volume models, to accurately predict mean follicle density in the ovarian cortex of healthy adult women.