Fatal tumoral hemorrhage from brain metastases of renal cell carcinoma after stereotactic radiotherapy and immune checkpoint inhibitor and vascular endothelial growth factor-targeted therapy combinations.

Introduction: Brain metastasis in renal cell carcinoma, which is reported in 10% of cases, leads to significant morbidity and mortality. Establishment of appropriate and safe treatment for brain metastasis renal cell carcinoma remains a pressing need. Case presentation: A 56-year-old female patient, presenting with anorexia, headache, and occipital swelling, was subsequently diagnosed with clear cell renal cell carcinoma with multiple metastases, including intracranial and epicranial tumors. The patient initially underwent stereotactic radiotherapy for metastatic brain tumors and then received combination therapy with pembrolizumab and lenvatinib. However, after 30 days of treatment, the patient experienced a sudden loss of consciousness due to massive multifocal intracranial hemorrhage, leading to her death the following day. Conclusion: Although fatal tumoral hemorrhage during combined stereotactic radiotherapy and immune checkpoint inhibitor/VEGF-targeted therapy for patients with brain metastasis renal cell carcinoma is an extremely rare complication, it should always be considered a possibility.

Remarkable Improvement of Diabetic Nephropathy in Transplanted Allograft after Kidney Transplantation.

Although glomerular damage caused by diabetic nephropathy was thought to be irreversible, in recent years, there have been reports on improvement in glomerular damage with strict glycemic control. However, few reports are available on the pathologic course after renal transplantation of donor-derived grafts with findings of diabetic nephropathy. A 53-year-old woman underwent an ABO blood-type compatible living-donor renal transplant. The recipient had no history of diabetes, and fasting blood glucose and hemoglobin A1c levels were both normal. The donor was a 57-year-old male who had received treatment for type 2 diabetes mellitus for 10 years. Transplant renal biopsy performed 1 h after revascularization showed mesangial matrix expansion and arterial hyalinosis due to diabetic nephropathy. The blood glucose level was within the normal range after transplantation. Mesangial matrix expansion and arterial hyalinosis disappeared in allograft biopsy samples 7 years after transplantation. We observed significant improvement in the pathological findings of donor-derived diabetic nephropathy after renal transplantation in the subsequent follow-ups.

D-Asparagine is an Ideal Endogenous Molecule for Measuring the Glomerular Filtration Rate.

Introduction: An ideal endogenous molecule for measuring glomerular filtration rate (GFR) is still unknown. However, a rare enantiomer of serine, d-serine, is useful in GFR measurement. This study explored the potential of other d-amino acids for kidney function assessment. Methods: This was a cross-sectional observational study of 207 living kidney transplant donors and recipients, for whom GFR was measured using clearance of inulin (C-in). Associations between levels of d-amino acids and GFR were analyzed using multivariate factor analysis. Fractional excretion (FE), a ratio of the clearance of a substance to C-in as a standard molecule, was calculated to monitor the excretion ratio after glomerular filtration. Dissociation from an ideal FE of 100% was assessed as a bias. Proportional bias against C-in was calculated using Deming regression. Results: Multivariate analysis identified the blood level of d-asparagine to reflect GFR. Means of blood d-asparagine and clearance of d-asparagine (C-d-Asn) were 0.21 µM and 65.0 ml/min per 1.73 m2, respectively. Inulin-based FE (FEin) of d-asparagine was 98.67% (95% confidence interval [CI]: 96.43-100.90%) and less biased than those of known GFR markers, such as FEin of creatinine (147.93 [145.39-150.46]; P < 0.001) and d-serine (84.84 [83.22-86.46]; P < 0.001). A proportional bias of C-d-Asn to C-in was -7.8% (95% CI, -14.5 to -0.6%), which was minor compared to those of clearance of creatinine (-34.5% [-37.9 to -31.0%]) and d-serine (21.2% [13.9-28.9]). Conclusion: D-Asparagine acts similar to inulin in the kidney. Therefore, d-asparagine is an ideal endogenous molecule that can be used for GFR measurement.

A Case Report of a Kidney Transplant Recipient With Organizing Pneumonia After Graft Loss.

We present a case of a 68-year-old male patient who underwent ABO-incompatible living kidney transplantation from his wife because of immunoglobulin A nephropathy 13 years ago. Over time, the patient showed a gradual decline in graft function and required reinitiation of hemodialysis because of fluid overload, which led to his admission to our hospital. An arteriovenous fistula was created, and subsequently, hemodialysis therapy was started. Because he had chronic cytomegalovirus retinopathy and thrombotic microangiopathy due to immunosuppressive therapy at admission, mycophenolate mofetil and tacrolimus were discontinued during hemodialysis initiation. Only low-dose prednisolone was continued. One week later, the patient had a fever, and chest computed tomography revealed bilateral pneumonia, which was not improved by antibiotics. The patient was diagnosed with organized pneumonia. After ruling out opportunistic infection, including pneumocystis pneumonia, increased doses of prednisolone resulted in the remission of organizing pneumonia.

Single-cell transcriptome analysis of a rat model of bilateral renal ischemia-reperfusion injury.

Ischemia-reperfusion injury (IRI) causes massive tissue damage. Renal IRI is the most common type of acute renal injury, and the defects caused by it may progress to chronic kidney disease (CKD). Rodent models of renal IRI, with various patterns, have been used to study the treatment of human kidney injury. A rat model of bilateral IRI, in which the bilateral kidney blood vessels are clamped for 60 min, is widely used, inducing both acute and chronic kidney disease. However, the molecular mechanisms underlying the effects of bilateral IRI on kidney cells have not yet been fully elucidated. This study aimed to perform a whole-transcriptome analysis of the IRI kidney using single-cell RNA sequencing. We found renal parenchymal cells, including those from the proximal tubule, the loop of Henle, and distal tubules, to be damaged by IRI. In addition, we observed significant changes in macrophage population. Our study delineated the detailed cellular and molecular changes that occur in the rat model of bilateral IRI. Collectively, our data and analyses provided a foundation for understanding IRI-related kidney diseases in rat models.

Everolimus Reduces Cancer Incidence and Improves Patient and Graft Survival Rates after Kidney Transplantation: A Multi-Center Study.

Kidney transplantation can prevent renal failure and associated complications in patients with end-stage renal disease. Despite the good quality of life, de novo cancers after kidney transplantation are a major complication impacting survival and there is an urgent need to establish immunosuppressive protocols to prevent de novo cancers. We conducted a multi-center retrospective study of 2002 patients who underwent kidney transplantation between 1965 and 2020 to examine patient and graft survival rates and cumulative cancer incidence in the following groups categorized based on specific induction immunosuppressive therapies: group 1, antiproliferative agents and steroids; group 2, calcineurin inhibitors (CNIs), antiproliferative agents and steroids; group 3, CNIs, mycophenolate mofetil, and steroids; and group 4, mammalian target of rapamycin inhibitors including everolimus, CNIs, mycophenolate mofetil, and steroids. The patient and graft survival rates were significantly higher in groups 3 and 4. The cumulative cancer incidence rate significantly increased with the use of more potent immunosuppressants, and the time to develop cancer was shorter. Only one patient in group 4 developed de novo cancer. Potent immunosuppressants might improve graft survival rate while inducing de novo cancer after kidney transplantation. Our data also suggest that everolimus might suppress cancer development after kidney transplantation.

Incidence and mortality of post-transplant lymphoproliferative disorders after kidney transplantation: A real-world retrospective analysis in Japan.

OBJECTIVES: Post-transplant lymphoproliferative disorder is a potentially life-threatening complication that has a greater risk of occurrence in the setting of immunosuppression and oncogenic viral infections after transplant surgery. Few studies have reported the cumulative incidence, histological subtypes and clinical outcomes of this disorder in kidney transplant recipients. METHODS: We retrospectively investigated 34 post-transplant lymphoproliferative disorder patients diagnosed out of the 1210 kidney transplant recipients who had undergone the surgery at the two largest centers in Japan between January 1983 and December 2017. RESULTS: A total of 32 patients (94.1%) developed late-onset post-transplant lymphoproliferative disorder (diagnosed 1 year after transplantation). The cumulative incidence rates were 0.76% and 1.59% at 5 and 10 years post-transplantation, respectively. The central nervous system was the most common site (35.3%, 12/34). Overall survival was similar between patients with and without central nervous system lesions (P = 0.676). Of all of the cases, 23.5% (8/34) were detected through cancer screening. Importantly, patients with screening-detected post-transplant lymphoproliferative disorder had better overall survival than those with the disorder who had been symptom detected (P = 0.0215). Overall survival was significantly reduced in patients who developed the disorder compared with those who did not (P = 0.0001). CONCLUSIONS: Post-transplant lymphoproliferative disorder was more likely to occur in the late post-transplantation period, which showed that long-term medical examination for transplant recipients is required. Based on our findings, we propose vigilant, long-term, cancer screening in kidney transplant recipients.

Measurement of glomerular filtration rate using endogenous d-serine clearance in living kidney transplant donors and recipients.

BACKGROUND: Endogenous molecules that provide an unbiased and a precise evaluation of kidney function are still necessary. We explored the potential of clearance of d-serine, a rare enantiomer of serine and a biomarker of kidney function, as a measure of glomerular filtration rate (GFR). METHODS: This was a cross-sectional observational study of 200 living kidney transplant donors and recipients enrolled between July 2019 and December 2020 in a single Japanese center, for whom GFR was measured by clearance of inulin (C-in). Clearance of d-serine (C-dSer) was calculated based on blood and urine levels of d-serine, as measured by two-dimensional high-performance liquid chromatography. Analytical performance was assessed by calculating biases. Utilizing data from 129 participants, we developed equations for C-in based on C-dSer and C-cre using a linear regression model, and the performance was validated in 68 participants. FINDINGS: The means of C-in and C-dSer were 66.7 and 55.7 mL/min/1.73 m2 of body surface area, respectively, in the entire cohort. C-dSer underestimated C-in with a proportional bias of 22.0% (95% confidence interval, 14.2-29.8%) and a constant bias of -1.24 (-5.78-3.31), whereas the proportional bias was minor to that of C-cre (34.6% [31.1-38.2%] and 2.47 (-1.18-6.13) for proportional and constant bias, respectively). Combination of C-dSer and C-cre measured C-in with an equation of 0.391 × C-dSer + 0.418 × C-cre + 3.852, which reduced the proportional bias (6.5% [-0.2-13.1%] and -4.30 [-8.87-0.28] for proportional and constant bias, respectively). In the validation dataset, this equation performed well with median absolute residual of 3.5 [2.3-4.8], and high ratio of agreement (ratios of 30% and 15% different from C-in [P30 and P15] of 98.5 [91.4-100] and 89.7 [80.0-95.2], respectively). INTERPRETATION: The smaller proportional bias compared to that of C-cre is an advantage of C-dSer as a measure of C-in. Combinational measurement of d-serine and creatinine, two endogenous molecules, has the potential to serve as a measure of GFR with precision and minor biases and can support important clinical decisions. FUNDING: Japan Society for the Promotion of Science (JSPS, grant number 17H04188), Japan Agency of Medical Research and Development (AMED, JP20gm5010001), Osaka Kidney Bank (OKF19-0010), Shiseido Co., Ltd and KAGAMI Inc.

Rapid deterioration of renal function following coronavirus disease 2019 in a renal transplant recipient.

Introduction: The coronavirus disease 2019 pandemic emerged in December 2019. Renal transplant recipients receiving chronic immunosuppression are considered to be at a high risk of infection. Aside from upper respiratory tract symptoms, coronavirus disease 2019 has also been reported to cause acute kidney injury in 20-50% of infected cases. Case presentation: A 62-year-old male renal transplant recipient presented with high fever, diarrhea, and cough, concurrent with rapid deterioration of graft function. The patient tested positive for coronavirus disease 2019. The pathological findings of the graft biopsy revealed diffuse flattening of tubular epithelial cells and extensive loss of the brush border in proximal tubular cells. Mycophenolate mofetil was discontinued and sotrovimab, remdesivir, intravenous immunoglobulin, and intravenous methylprednisolone were administered, resulting in gradual improvements in clinical symptoms and renal function. Conclusion: We describe a case of a coronavirus disease 2019-infected kidney transplant recipient who developed severe acute kidney injury caused by severe acute tubular necrosis.

[A Case of Urinary Incontinence Due to Ectopic Ureter with Complete Urteral Duplication Successfully Treaeted by Transcatheter Arterial Embolization (TAE)].

A 22-year-old woman who was referred to our hospital presented with a complaint of urinary incontinence since childhood. Abdominal contrast-enhanced computed tomography revealed complete duplication of the left ureter. In addition, the upper half of the left kidney showed poor contrast, accompanied by signs of hydronephrosis. Magnetic resonance urography failed to show an opening between the upper half of the left kidney and the ectopic ureter. Cystoscopy revealed two normally positioned ureteral orifices. After intravenous injection of indigo carmine, however, the dye became evident in the vagina. Thus, she was diagnosed to have urinary incontinence due to complete duplication of the left ureter and an ectopic ureteral opening into the vagina. Transcatheter arterial embolization of the upper half of the kidney, the origin of the ectopic ureter, immediately relieved the patient of urinary incontinence. At the 6-month follow-up, the patient had experienced no recurrence or complications.

Systemic vs. intrathecal central nervous system prophylaxis in primary adrenal/renal diffuse large b-cell LYMPHOMA: A multi-institution retrospective analysis and systematic review.

Primary adrenal lymphoma (PAL) and primary renal lymphoma (PRL) are rare extranodal lymphomas, predominantly of diffuse large B-cell lymphoma subtype. Primary adrenal and renal lymphomas (PARL) exhibit a high predilection for the central nervous system (CNS). Therefore, current guidelines support the use of CNS prophylaxis in PARL, particularly in cases of high-risk Central Nervous System International Prognostic Index (CNS-IPI). However, the route of administration (i.e. systemic vs. intrathecal chemotherapy) has not been clearly elucidated. With this in mind, we initiated an international collaboration and literature review to analyze 50 patient cases, 20 of which received CNS prophylaxis. Based on our analysis, we conclude that PARL may indicate a need for CNS chemo-prophylaxis in the form of systemic high-dose methotrexate (HD-MTX) over intrathecal methotrexate (IT-MTX), although IT-MTX may still have utility in certain cases.

Structural dynamics of the chromo-shadow domain and chromodomain of HP1 bound to histone H3K9 methylated peptide, as measured by site-directed spin-labeling EPR spectroscopy.

The structural dynamics of the chromo-shadow domain (CSD) and chromodomain (CD) of human HP1 proteins essential for heterochromatin formation were investigated at the nanosecond and nanometer scales by site-directed spin labeling electron paramagnetic resonance and pulsed double resonance spectroscopy. Distance measurements showed that the spin-labeled CSD of human HP1α and HP1γ tightly dimerizes. Unlike CD-CD interaction observed in fission yeast HP1 in an inactivated state (Canzio et al., 2013), the two CDs of HP1α and HP1γ were spatially separated from each other, dynamically mobile, and ready for a Brownian search for H3K9-tri-methyl(me3) on histones. Complex formation of the CD with H3K9me3 slowed dynamics of the domain due to a decreased diffusion constant. CSD mobility was significantly (∼1.3-fold) lower in full-length HP1α than in HP1γ, suggesting that the immobilized conformation of human HP1α shows an auto-inactivated state. Differential properties of HP1α and HP1γ to form the inactive conformation could be relevant to its physiological role in the heterochromatin formation in a cell.

Cumulative cancer incidence and mortality after kidney transplantation in Japan: A long-term multicenter cohort study.

Kidney transplantation is the most promising treatment to improve mortality and life quality in end-stage kidney disease; however, cancer remains a leading cause of death. Several factors including immunosuppressants might be associated with a gradual increase in cumulative cancer incidence after kidney transplantation. Risk factors for cancer and overall and cancer-specific survival were analyzed in 1973 kidney transplant recipients from three study institutions in Japan. The 5-, 10-, 20-, and 30-year overall and cancer-specific survival rates were 93.3%, 88.4%, 78.0%, and 63.6% and 99.4%, 98.0%, 95.3%, and 91.7%, respectively. The overall survival rate was significantly higher and the graft survival rate was significantly lower in recipients without cancer than in those with cancer. Older recipient age, longer dialysis duration before kidney transplantation, and history of transfusion were significant predictors of cancer. Dialysis duration before kidney transplantation was a prognostic factor of overall survival rate. Regarding cancer-specific survival rates, older recipient age and dialysis duration before kidney transplantation were prognostic factors of worse cancer-specific survival rates. The type of immunosuppressant was not associated with an increased cancer rate. Aggressiveness of immunosuppressant regimens or potent immunosuppressants might improve graft survival rate while inducing de novo cancer after kidney transplantation. Older age and longer dialysis duration before kidney transplantation were risk factors of cancer-specific survival rate.

Recurrence of Proliferative Glomerulonephritis with Monoclonal Immunoglobulin G Deposits with a Striated Ultrastructure.

A 64-year-old man with nephrotic syndrome was admitted to another hospital where his renal biopsy revealed membranoproliferative glomerulonephritis (MPGN) with monoclonal immunoglobulin (Ig) G, subclass 1, κ light chain (IgG1κ) deposition on immunofluorescence (IF). Proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) was suspected due to monoclonal IgG1κ deposits and the absence of hematological abnormalities. However, the typical PGNMID phenotype was not observed by electron microscopy. Instead, an organized and striated muscle-like structure was observed in the subendothelial space. Since a 2-year treatment with immunosuppressants did not improve his proteinuria, a second biopsy was performed at our hospital. It showed an MPGN-like phenotype; however, monoclonal Ig deposits on IF were no longer observed. One year after the second biopsy, he developed ESRD. Thus, he underwent living kidney transplantation from his wife. Allograft biopsy was performed as proteinuria was observed 3 months after transplantation, which again showed an MPGN-like phenotype with monoclonal IgG1κ deposits. The observed electron-dense deposits were similar to those in the native biopsies. Accordingly, the patient was diagnosed with recurrent MPGN. Adding methylprednisolone pulse therapy to conventional immunosuppressants did not improve the patient's renal function or proteinuria. He died of Legionella pneumonia 8 months after transplantation. Considering the patient's histological findings of MPGN with monoclonal IgG1κ deposits and early recurrence of glomerulonephritis after transplantation, he was diagnosed with PGNMID with novel electron-dense deposits.

Efficacy of a Si-based agent against developing renal failure in a rat remnant kidney model.

Chronic renal failure is exacerbated by oxidative stress, and this condition is difficult to treat in advanced stages. Because of the lack of effective treatments, the disease is a global public health concern. We developed a Si-based agent that continuously generates hydrogen for more than 24 h by reacting with water under conditions similar to those in the gastrointestinal tract. Given the efficacy of hydrogen in the treatment of conditions associated with oxidative stress, we examined whether the Si-based agent had beneficial effects on the development of renal failure. The Si-based agent was orally administered to rats that were developing renal failure. Rats underwent 5/6 nephrectomy to establish a remnant kidney model. Specifically, on day -7, rats underwent right 2/3 nephrectomy, followed by light nephrectomy on day 0. Starting on day -3, the rats were administered a control or Si-based agent-containing diet for 8 weeks. Compared with the findings in control rats, the Si-based agent greatly suppressed the increases of both serum creatinine and urinary protein levels. All analyzed parameters of oxidative stress were significantly suppressed in the Si-based agent groups. Histopathological examination illustrated that glomerular hypertrophy was suppressed by the treatment. Quantitative real-time reverse transcription-polymerase chain reaction revealed that sirtuin 1 and heme oxygenase-1 expression was increased in the Si-based agent groups, suggesting improved antioxidant activity and reduced hypoxia. In addition, caspase-3 and interleukin-6 expression was suppressed in the Si-based agent groups, indicating the alleviation of apoptosis and inflammation. In conclusion, oral administration of a Si-based agent resulted in renoprotective effects, presumably by suppressing oxidative stress via hydrogen generation.

Clinical Efficacy of Intravenous Immunoglobulin for BK Polyomavirus-Associated Nephropathy After Living Kidney Transplantation.

PURPOSE: BK polyomavirus (BKPyV)-associated nephropathy (BKPyVAN) is one of the most difficult infections to be treated after kidney transplantation. Although patients with BKPyVAN usually received a reduction of immunosuppressive agents, the majority of these patients undergo the loss of the graft kidney without any effective treatment afterward. Therefore, development of more effective therapy for BKPyVAN is eagerly expected. PATIENTS AND METHODS: Among patients who underwent a kidney transplantation between January 2016 and April 2019 at our hospital, there were five cases of BKPyVAN. After the initial diagnosis, all patients discontinued administration of mycophenolate mofetil (MMF), which was not enough to diminish decoy cells in urine cytology test. Therefore, all patients received additional intravenous immunoglobulin (IVIG) (100 mg/kg/day) therapy for five days and were evaluated for the therapeutic effect of IVIG with immunohistochemical examination using re-biopsy samples of the graft kidney. RESULTS: After IVIG therapy, 2 cases showed negative decoy cells in urine and 3 cases showed a drastic decrease of plasma BK virus load. Importantly, simian virus (SV) 40 large T antigens diminished after IVIG administration in all cases, which degraded polyomavirus nephropathy classification. CONCLUSION: Although it is difficult to treat BKPyVAN after kidney transplant, IVIG therapy was considered to a promising treatment to improve severity of BKPyVAN especially in cases that dose reduction of immunosuppressive agents was ineffective.

Therapeutic Effects and Functional Mechanism of Intravenous Immunoglobulin in Preclinical Rat Renal Transplant Model of Antibody-Mediated Rejection.

BACKGROUND: Intravenous immunoglobulin (Ig) therapy is used based on empirical findings for treatment of antibody-mediated rejection (AMR) in cases of renal transplantation, although its therapeutic efficacy has not been proven and the functional mechanism of an administered Ig remains elusive. In this study, the therapeutic effects of an Ig were examined in a preclinical rat renal transplant model of AMR to investigate this mechanism. METHODS: To establish an AMR renal graft model, skin graft specimens were obtained from Brown-Norway (BN) rats and transplanted to Lewis rats to produce donor-specific antibodies (DSAs), after which kidney transplantation from the Brown-Norway to Lewis rats was performed. AMR model rats were administered the Ig at a dose of 2 g/kg or saline as a control. Survival period, renal graft histopathology, complement factors, and DSA levels were assessed. RESULTS: The survival period of the group administered the Ig was significantly prolonged. Histopathological examinations of renal grafts also showed significant suppression of glomerulitis and peritubular capillaritis in the Ig group, and real-time polymerase chain reaction analysis results demonstrated significantly lower levels of expression of the complement factors C1q and C3. When the Ig was given to rats that underwent skin grafting but not renal transplantation, DSA was decreased after 6 hours and remained lower than the baseline level for at least 7 days. CONCLUSION: Ig administration suppressed DSA production. The present results showed that suppression of the complement system contributed to effective Ig treatment for AMR.

Oral Administration of Si-Based Agent Attenuates Oxidative Stress and Ischemia-Reperfusion Injury in a Rat Model: A Novel Hydrogen Administration Method.

Organ ischemia-reperfusion injury (IRI), which is unavoidable in kidney transplantation, induces the formation of reactive oxygen species and causes organ damage. Although the efficacy of molecular hydrogen (H2) in IRI has been reported, oral intake of H2-rich water and inhalation of H2 gas are still not widely used in clinical settings because of the lack of efficiency and difficulty in handling. We successfully generated large quantities of H2 molecules by crushing silicon (Si) to nano-sized Si particles (nano-Si) which were allowed to react with water. The nano-Si or relatively large-sized Si particles (large-Si) were orally administered to rats with renal IRI. Animals were divided into four groups: sham, IRI, IRI + nano-Si, and IRI + large-Si. The levels of serum creatinine and urine protein were significantly decreased 72 h following IRI in rats that were administered nano-Si. The levels of oxidative stress marker, urinary 8-hydroxydeoxyguanosine were also significantly decreased with the nano-Si treatment. Transcriptome and gene ontology enrichment analyses showed that the oral nano-Si intake downregulated the biological processes related to oxidative stress, such as immune response, cytokine production, and extrinsic apoptotic signaling pathway. Alterations in the regulation of a subset of genes in the altered pathways were validated by quantitative polymerase chain reaction. Furthermore, immunohistochemical analysis demonstrated that the nano-Si treatment alleviated interstitial macrophage infiltration and tubular apoptosis, implicating the anti-inflammatory and anti-apoptotic effects of nano-Si. In conclusion, renal IRI was attenuated by the oral administration of nano-Si, which should be considered as a novel H2 administration method.

Trityl-Aryl-Nitroxide-Based Genuinely g-Engineered Biradicals, As Studied by Dynamic Nuclear Polarization, Multifrequency ESR/ENDOR, Arbitrary Wave Generator Pulse Microwave Waveform Spectroscopy, and Quantum Chemical Calculations.

Trityl and nitroxide radicals are connected by π-topologically controlled aryl linkers, generating genuinely g-engineered biradicals. They serve as a typical model for biradicals in which the exchange (J) and hyperfine interactions compete with the g-difference electronic Zeeman interactions. The magnetic properties underlying the biradical spin Hamiltonian for solution, including J's, have been determined by multifrequency CW-ESR and 1H ENDOR spectroscopy and compared with those obtained by quantum chemical calculations. The experimental J values were in good agreement with the quantum chemical calculations. The g-engineered biradicals have been tested as a prototype for AWG (Arbitrary Wave Generator)-based spin manipulation techniques, which enable GRAPE (GRAdient Pulse Engineering) microwave control of spins in molecular magnetic resonance spectroscopy for use in molecular spin quantum computers, demonstrating efficient signal enhancement of specific weakened hyperfine signals. Dynamic nuclear polarization (DNP) effects of the biradicals for 400 MHz nuclear magnetic resonance signal enhancement have been examined, giving efficiency factors of 30 for 1H and 27.8 for 13C nuclei. The marked DNP results show the feasibility of these biradicals for hyperpolarization.

Quantum chemistry on quantum computers: quantum simulations of the time evolution of wave functions under the S2 operator and determination of the spin quantum number S.

Quantum computers have an enormous impact on quantum chemical calculations. Approaches to calculate the energies of atoms and molecules on quantum computers by utilizing quantum phase estimation (QPE) and the variational quantum eigensolver (VQE) have been well documented, and dozens of methodological improvements to decrease computational costs and to mitigate errors have been reported until recently. However, the possible methodological implementation of observables on quantum computers such as calculating the spin quantum numbers of arbitrary wave functions, which is a crucial issue in quantum chemistry, has been discussed less. Here, we propose a quantum circuit to simulate the time evolution of wave functions under an S2 operator, exp(-iS2t)|Ψ, and integrate it into the QPE circuit enabling us to determine the spin quantum number of the arbitrary wave functions. We demonstrate that the spin quantum numbers of up to three spins can be determined by only one qubit measurement in QPE.