Impact of Asialoglycoprotein Receptor and Mannose Receptor Deficiency on Murine Plasma N-glycome Profiles.

The asialoglycoprotein receptor (ASGPR) and the mannose receptor C-type 1 (MRC1) are well known for their selective recognition and clearance of circulating glycoproteins. Terminal galactose and N-Acetylgalactosamine are recognized by ASGPR, while terminal mannose, fucose, and N-Acetylglucosamine are recognized by MRC1. The effects of ASGPR and MRC1 deficiency on the N-glycosylation of individual circulating proteins have been studied. However, the impact on the homeostasis of the major plasma glycoproteins is debated and their glycosylation has not been mapped with high molecular resolution in this context. Therefore, we evaluated the total plasma N-glycome and plasma proteome of ASGR1 and MRC1 deficient mice. ASGPR deficiency resulted in an increase in O-acetylation of sialic acids accompanied by higher levels of apolipoprotein D, haptoglobin, and vitronectin. MRC1 deficiency decreased fucosylation without affecting the abundance of the major circulating glycoproteins. Our findings confirm that concentrations and N-glycosylation of the major plasma proteins are tightly controlled and further suggest that glycan-binding receptors have redundancy, allowing compensation for the loss of one major clearance receptor.

Cancer care in transgender and gender-diverse persons: results from two national surveys among providers and health service users by the Italian Association of Medical Oncology.

BACKGROUND: Transgender and gender-diverse (TGD) population represents an underserved group across the cancer care continuum. To assess the perspective of both oncology health care providers (OHPs) and TGD individuals in Italy, we conducted two national surveys: one among 2407 OHPs about their attitudes, knowledge and behavior toward TGD patients, and one among TGD persons about their health needs, experiences and barriers encountered in the use of health services across the cancer continuum. MATERIALS AND METHODS: The surveys were self-compiled web-based computer-aided web interview, conducted in Italy within the 'OncoGender-Promoting Inclusion in Oncology' project, led by the Italian national cancer society [Associazione Italiana di Oncologia Medica (AIOM)]-associated researchers. All members of AIOM were invited by e-mail to participate in the OHP survey. TGD persons were reached through advocacy groups and consumers' panel. The recruitment was completed on a voluntary basis. Survey data were collected and managed using an online platform managed by ELMA Research, an independent pharmaceutical marketing agency. RESULTS: A total of 305 OHPs (13% of AIOM members) and 190 TGD individuals participated in the surveys. Only 19% of OHPs felt competent in providing care to TGD patients and 21% declared not to feel comfortable in treating TGD patients. Seventy-one percent of TGD persons reported that they had never joined any cancer screening program; 32% reported one or more acts of discrimination by health care providers. Seventy-two percent of OHPs recognized the lack of specific education on cancer care for TGD patients and deemed it necessary to receive adequate training. CONCLUSIONS: A general lack of knowledge among OHPs about TGD health issues seems to be the main driver of difficulties in providing assistance and of discriminatory attitudes against TGD individuals. Ultimately, this whole issue generates access barriers and contributes to lack of trust in health care services. Educational interventions and an implementation of person-centric cancer policies are urgently needed.

Vaccination for seasonal influenza, pneumococcal infection and SARS-CoV-2 in patients with solid tumors: recommendations of the Associazione Italiana di Oncologia Medica (AIOM).

Patients with cancer have a well-known and higher risk of vaccine-preventable diseases (VPDs). VPDs may cause severe complications in this setting due to immune system impairment, malnutrition and oncological treatments. Despite this evidence, vaccination rates are inadequate. The Italian Association of Medical Oncology [Associazione Italiana di Oncologia Medica (AIOM)] has been involved in vaccination awareness since 2014. Based on a careful review of the available data about the immunogenicity, effectiveness and safety of flu, pneumococcal and anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, we report the recommendations of the AIOM about these vaccinations in adult patients with solid tumors. The AIOM recommends comprehensive education on the issue of VPDs. We believe that a multidisciplinary care model may improve the vaccination coverage in immunocompromised patients. Continued surveillance, implementation of preventive practices and future well-designed immunological prospective studies are essential for better management of our patients with cancer.

Position paper of the Italian Association of Medical Oncology on the impact of COVID-19 on Italian oncology and the path forward: the 2021 Matera statement.

The coronavirus disease 2019 (COVID-19) pandemic has severely affected cancer care and research by disrupting the prevention and treatment paths as well as the preclinical, clinical, and translational research ecosystem. In Italy, this has been particularly significant given the severity of the pandemic's impact and the intrinsic vulnerabilities of the national health system. However, whilst detrimental, disruption can also be constructive and may stimulate innovation and progress. The Italian Association of Medical Oncology (AIOM) has recognized the impact of COVID-19 on cancer care continuum and research and proposes the '2021 Matera statement' which aims at providing pragmatic guidance for policymakers and health care institutions to mitigate the impact of the global health crisis on Italian oncology and design the recovery plan for the post-pandemic scenario. The interventions are addressed both to the pillars (prevention, diagnosis, treatment, follow-up, health care professionals) and foundations of cancer care (communication and care relationship, system organization, resources, research, networking). The priorities to be implemented can be summarized in the MATERA acronym: Multidisciplinarity; Access to cancer care; Telemedicine and Territoriality; Equity, ethics, education; Research and resources; Alliance between stakeholders and patients.

The molecular profiling of solid tumors by liquid biopsy: a position paper of the AIOM-SIAPEC-IAP-SIBioC-SIC-SIF Italian Scientific Societies.

The term liquid biopsy (LB) refers to the use of various biological fluids as a surrogate for neoplastic tissue to achieve information for diagnostic, prognostic and predictive purposes. In the current clinical practice, LB is used for the identification of driver mutations in circulating tumor DNA derived from both tumor tissue and circulating neoplastic cells. As suggested by a growing body of evidence, however, there are several clinical settings where biological samples other than tissue could be used in the routine practice to identify potentially predictive biomarkers of either response or resistance to targeted treatments. New applications are emerging as useful clinical tools, and other blood derivatives, such as circulating tumor cells, circulating tumor RNA, microRNAs, platelets, extracellular vesicles, as well as other biofluids such as urine and cerebrospinal fluid, may be adopted in the near future. Despite the evident advantages compared with tissue biopsy, LB still presents some limitations due to both biological and technological issues. In this context, the absence of harmonized procedures corresponds to an unmet clinical need, ultimately affecting the rapid implementation of LB in clinical practice. In this position paper, based on experts' opinions, the AIOM-SIAPEC-IAP-SIBIOC-SIF Italian Scientific Societies critically discuss the most relevant technical issues of LB, the current and emerging evidences, with the aim to optimizing the applications of LB in the clinical setting.

Early prediction of pancreatic cancer from new-onset diabetes: an Associazione Italiana Oncologia Medica (AIOM)/Associazione Medici Diabetologi (AMD)/Società Italiana Endocrinologia (SIE)/Società Italiana Farmacologia (SIF) multidisciplinary consensus position paper.

Pancreatic cancer (PC) is a common cause of cancer-related death, due to difficulties in detecting early-stage disease, to its aggressive behaviour, and to poor response to systemic therapy. Therefore, developing strategies for early diagnosis of resectable PC is critical for improving survival. Diabetes mellitus is another major public health problem worldwide. Furthermore, diabetes can represent both a risk factor and a consequence of PC: nowadays, the relationship between these two diseases is considered a high priority for research. New-onset diabetes can be an early manifestation of PC, especially in a thin adult without a family history of diabetes. However, even if targeted screening for patients at higher risk of PC could be a promising approach, this is not recommended in asymptomatic adults with new-onset diabetes, due to the much higher incidence of hyperglycaemia than PC and to the lack of a safe and affordable PC screening test. Prompted by a well-established and productive multidisciplinary cooperation, the Italian Association of Medical Oncology (AIOM), the Italian Medical Diabetologists Association (AMD), the Italian Society of Endocrinology (SIE), and the Italian Society of Pharmacology (SIF) here review available evidence on the mechanisms linking diabetes and PC, addressing the feasibility of screening for early PC in patients with diabetes, and sharing a set of update statements with the aim of providing a state-of-the-art overview and a decision aid tool for daily clinical practice.

Antineoplastic dosing in overweight and obese cancer patients: an Associazione Italiana Oncologia Medica (AIOM)/Associazione Medici Diabetologi (AMD)/Società Italiana Endocrinologia (SIE)/Società Italiana Farmacologia (SIF) multidisciplinary consensus position paper.

Most anticancer molecules are administered in body-size-based dosing schedules, bringing up unsolved issues regarding pharmacokinetic data in heavy patients. The worldwide spread of obesity has not been matched by improved methods and strategies for tailored drug dosage in this population. The weight or body surface area (BSA)-based approaches may fail to fully reflect the complexity of the anthropometric features besides obesity in cancer patients suffering from sarcopenia. Likewise, there is a lack of pharmacokinetic data on obese patients for the majority of chemotherapeutic agents as well as for new target drugs and immunotherapy. Therefore, although the available findings point to the role of dose intensity in cancer treatment, and support full weight-based dosing, empirical dose capping often occurs in clinical practice in order to avoid toxicity. Thus a panel of experts of the Associazione Italiana Oncologia Medica (AIOM), Associazione Medici Diabetologi (AMD), Società Italiana Endocrinologia (SIE), and Società Italiana Farmacologia (SIF), provides here a consensus statement for appropriate cytotoxic chemotherapy and new biological cancer drug dosing in obese patients.

COVID-19 infection in cancer patients: what has been the contribution of Associazione Italiana Oncologia Medica (AIOM) to oncological care since the beginning of the first pandemic wave?

High mortality rates in elderly patients or in those with underlying chronic illnesses and/or a compromised immune system is a peculiar feature of COVID-19 infection. The possible coexistence of a cancer and COVID-19 infection in the same individual prompted concerns regarding their synergistic effect on prognosis. In order to balance patients' needs with the risks related to the infection, the question oncologists have asked from the beginning of the first wave of the pandemic has been: 'how can we deal with COVID-19 infection in cancer patients?' In pursuing its mission, the Associazione Italiana Oncologia Medica (AIOM) has made every possible effort to support cancer patients, health care professionals and institutions in the decision-making processes the pandemic has engendered within this scenario. The relevant documents as well as the educational and institutional initiatives the AIOM has taken are reported in this article.

Functional Improvement After Outpatient Cardiac Rehabilitation in Acute Coronary Syndrome Patients is Not Related to Improvement in Left Ventricular Ejection Fraction.

INTRODUCTION: Cardiac rehabilitation (CR) improves the functional capacity and the prognosis of patients with coronary artery disease. AIM: Our study was aimed at assessing the relationship between functional improvement (evaluated with 6-min Walk Test-6MWT) and the improvement in left ventricular ejection fraction (LVEF) after CR. METHODS: We collected data from 249 patients (age 66.79 ± 11.06 years; males 81.52%) with a recent history of Acute Coronary Syndrome that performed CR. The functional improvement after CR was expressed as the Δ between distance covered at the final versus the initial 6-min Walking Test (6-MWT), while LVEF was calculated with transthoracic echocardiogram at the beginning and at the end of the CR. RESULTS: Patients were divided accordingly to their pre-rehab LVEF (≥ 55% vs < 55%). With superimposable age and baseline 6MWT distance covered (434.58 vs 405.12 m, p = 0.08), the latter group presented higher Δ meter values at 6MWT (167.93 vs 193.97 m, p = 0.018). However, no statistically significant positive correlation between Δ meters and Δ LVEF was found. Moreover, linear regression analyses found that nor baseline LVEF nor Δ LVEF were significant determinants of Δ meters when considering the whole group, with age, basal 6MWT and peak CK-MB as additional covariates in the model. CONCLUSION: Although it could be expected that an increase in LVEF is related to the functional improvement after CR, no significant correlation was found in our population.

Leopoldia comosa prevents metabolic disorders in rats with high-fat diet-induced obesity.

PURPOSE: Obesity is the main feature of a complex illness known as metabolic syndrome. Anti-obesogenic therapies are often associated with side effects and represent a high cost in conventional pharmacological approaches. New strategies based on natural remedies are under continuous investigation. Leopoldia comosa (L.) Parl. (L. comosa) is a spontaneous plant with diuretic, anti-inflammatory and antioxidant properties. Recently, a hypoglycemic activity mediated by inhibition of carbohydrate digestion has been identified. The aim of this study was to evaluate the effects of a diet supplemented with L. comosa extracts on a rat model of diet-induced obesity. METHODS: Leopoldia comosa bulb extracts were obtained using a dynamic extractor. Phytochemical properties and in vitro determination of the antioxidant activity and of the inhibitory effects on lipase and pancreatic amylase were performed. Rats were fed (12 weeks) a standard diet, or a high-fat diet (HFD), or an HFD plus L. comosa (20 or 60 mg/die) extracts. The metabolic and anthropometric parameters were recorded. RESULTS: Results indicated that L. comosa inhibited lipase and pancreatic amylase activities. In vivo data showed that the supplementation with both doses of L. comosa extracts counteracted the HFD-dependent effects. It reduced body weight, abdominal obesity and dyslipidemia, and improved glucose tolerance with a reduction of lipidic tissue hypertrophy and liver steatosis, as compared to HFD-fed rat. In liver, L. comosa reduced protein expression levels of PEPCK and G6Pase. CONCLUSION: We suggest that L. comosa extracts prevent obesity-dependent metabolic disorders. This paves the way for their therapeutic application as a natural anti-obesity drug.

Steepest-entropy-ascent nonequilibrium quantum thermodynamic framework to model chemical reaction rates at an atomistic level.

The steepest entropy ascent (SEA) dynamical principle provides a general framework for modeling the dynamics of nonequilibrium (NE) phenomena at any level of description, including the atomistic one. It has recently been shown to provide a precise implementation and meaning to the maximum entropy production principle and to encompass many well-established theories of nonequilibrium thermodynamics into a single unifying geometrical framework. Its original formulation in the framework of quantum thermodynamics (QT) assumes the simplest and most natural Fisher-Rao metric to geometrize from a dynamical standpoint the manifold of density operators, which represent the thermodynamic NE states of the system. This simplest SEAQT formulation is used here to develop a general mathematical framework for modeling the NE time evolution of the quantum state of a chemically reactive mixture at an atomistic level. The method is illustrated for a simple two-reaction kinetic scheme of the overall reaction F+H_{2}⇔HF+F in an isolated tank of fixed volume. However, the general formalism is developed for a reactive system subject to multiple reaction mechanisms. To explicitly implement the SEAQT nonlinear law of evolution for the density operator, both the energy and the particle number eigenvalue problems are set up and solved analytically under the dilute gas approximation. The system-level energy and particle number eigenvalues and eigenstates are used in the SEAQT equation of motion to determine the time evolution of the density operator, thus effectively describing the overall kinetics of the reacting system as it relaxes toward stable chemical equilibrium. The predicted time evolution in the near-equilibrium limit is compared to the reaction rates given by a standard detailed kinetic model so as to extract the single time constant needed by the present SEA model.

Estimating 12-week death probability in patients with refractory metastatic colorectal cancer: the Colon Life nomogram.

Background: Regorafenib and TAS-102 have recently demonstrated statistically significant survival gains in patients with refractory metastatic colorectal cancer (mCRC). Life expectancy ≥12 weeks was an inclusion criterion in registrative trials, and the identification of proper clinical selection tools for the daily use of these drugs in heavily pre-treated patients is needed to improve the cost-benefit ratio. We aimed at building a nomogram able to predict death probability within 12 weeks from the date of assessment of refractory mCRC. Patients and methods: Four hundred eleven refractory mCRC patients with ECOG performance status (PS) ≤2 receiving regorafenib, TAS-102 or other treatments were used as developing set. Putative prognostic variables were selected using a random forest model and included in a binary logistic model from which the nomogram was developed. The nomogram was externally validated and its performance was evaluated by examining calibration (how close predictions were to the actual outcome) and discriminative ability (Harrell C index) both on developing (internal validation) and validating (external validation) sets. Results: Four variables were selected and included in the nomogram: PS (P < 0.0001), primary tumor resection (P = 0.027), LDH value (P = 0.0001) and peritoneal involvement (P = 0.081). In the developing set, the nomogram discriminative ability was high (C = 0.778), and was confirmed in the validating set (C = 0.778), where the overall outcome was better as a consequence of the enrichment in patients receiving regorafenib or TAS-102 (46% versus 34%; P < 0.0001). Conclusions: Our nomogram may be a useful tool to predict the probability of death within 12 weeks in patients with refractory mCRC. Based on four easy-to-collect variables, the 'Colon Life' nomogram and free app for smartphones may improve mCRC patients' selection for later-line therapies and assist researchers for the enrollment in clinical trials in this setting.

GC-MS characterisation and biological activity of essential oils from different vegetative organs of Plectranthus barbatus and Plectranthus caninus cultivated in north Italy.

Essential oils (EOs) from the roots, stems and leaves of Plectranthus barbatus (A) and Plectranthus caninus (B), cultivated in north Italy, were obtained by steam distillation and chemically characterised by gas chromatography-mass spectrometry. The highest yields were obtained from roots (268.15 and 673.60 mg/kg from A and B), followed by leaves (64.34 and 26.65 mg/kg) and stems (19.76 and 18.63 mg/kg). A total of 128 structures were identified in A and 121 in B. Fe(++) chelating and antiradical activities (DPPH and ABTS) were evaluated: root and stem EOs showed the strongest activities, while EOs from leaves did not show relevant activities. All EOs were tested for their in vitro antimicrobial activity, showing optimal growth-inhibition in antibiogram (∅>35 mm) and MIC tests (32-64 µg/mL) against Candida albicans, while EOs from leaves of both species showed a good activity (25 < ∅ < 34 mm, MIC 64-128 µg/mL) against Escherichia coli.

Prognostic factors in elderly patients with malignant pleural mesothelioma: results of a multicenter survey.

BACKGROUND: The incidence of malignant pleural mesothelioma (MPM) in elderly patients is increasing. There are no specific guidelines for their management. METHODS: The clinical records of elderly patients (⩾70 years old) with MPM referred from January 2005 to November 2011 to six Italian Centres were reviewed. Age, gender, histology, International Mesothelioma Interest Group (IMIG) stage, Eastern Cooperative Oncology Group Performance Status (ECOG-PS), Charlson Comorbidity Index (CCI) and treatment modalities were analysed and correlated to overall survival (OS). RESULTS: In total, 241 patients were identified. Charlson Comorbidity Index was ⩾1 in 92 patients (38%). Treatment was multimodality therapy including surgery in 18, chemotherapy alone in 180 (75%) and best supportive care in 43 cases (18%). Chemotherapy was mainly pemetrexed based. Median OS was 11.4 months. Non-epithelioid histology (HR 2.32; 95% CI 1.66-3.23, P<0.001), age ⩾75 years (HR 1.44; 95% CI 1.08-1.93, P=0.014), advanced (III-IV) stage (HR 1.47; 95% CI 1.09-1.98, P=0.011) and CCI⩾1 (HR 1.38; 95% CI 1.02-1.85, P=0.034) were associated to a shorter OS. Treatment with pemetrexed was associated with improved OS (HR 0.40; 95% CI 0.28-0.56, P<0.001). CONCLUSIONS: Non-epithelioid histology, age ⩾75 years, advanced IMIG stage and presence of comorbidities according to CCI were significant prognostic factors in elderly patients with MPM. Treatment with pemetrexed-based chemotherapy was feasible in this setting. Prospective dedicated trials in MPM elderly patients selected according to prognostic factors including comorbidity scales are warranted.

Controlling the alien hand through the mirror box. A single case study of alien hand syndrome.

Disruption of motor control in the alien hand syndrome might result from a dissociation between intentions and sensory information. We hypothesized that voluntary motor control in this condition could improve by restoring the congruency between motor intentions and visual feedback. The present study shows that, in one patient with right alien hand syndrome, the use of a mirror box paradigm improved motor speed. We speculate that the visual feedback provided by the mirror increases the sense of congruence between intention and sensory feedback, leading to motor improvement.

Neurological recovery after out-of-hospital cardiac arrest: hospital admission predictors and one-year survival in an urban cardiac network experience.

AIM: The aim of the study was to detect early predictors of neurological recovery and evaluate one year survival related to neurological status at discharge in patients (pts) admitted after out of hospital cardiac arrest (OHCA). METHODS: Sixty-three consecutive pts with OHCA from any cardiac cause, admitted to our cardiac intensive care unit, were classified according to survival and cerebral performance category (CPC) scale from 1 to 4 at hospital discharge. Pre-hospital and emergency room (ER) variables were analyzed to identify early predictors of neurological recovery as defined CPC=1-2. RESULTS: Overall in-hospital survival was 60%. Sixty-eight and 32% of survivors were classified as CPC 1-2 and CPC 3-4 respectively. During one year follow-up 96% of patients classified as CPC 1-2 survived and 100% of CPC 3-4 died. Emergency crew witnessing, performance of cardio pulmonary resuscitation (CPR) by witnesses, the call for chest pain, no history of heart disease and a Glasgow coma scale (GCS) of ≥9 on arrival to the ER, were more frequent in patients classified as CPC 1-2 and times from "OHCA to return of spontaneous circulation (ROSC)", from "emergency medical system (EMS) arrival to ROSC" and "first DC shock to ROSC" were also significantly shorter in these patients. The time of first DC shock to ROSC in pts who presented with rhythm in ventricular fibrillation and the time from OHCA to ROSC in pts with witnessed OHCA were an independent predictors of neurological recovery. CONCLUSION: Forty-one percent of pts admitted to our tertiary centre after OHCA were discharged with CPC 1-2 and at one year follow-up 96% of these were alive, while all pts classified as CPC 3-4 died. Easily documented information such as the time from OHCA to ROSC and the time of first shock to ROSC are early independent predictors of neurological recovery.

Camptothecin resistance in cancer: insights into the molecular mechanisms of a DNA-damaging drug.

Poisoning of DNA topoisomerase I is the mechanism by which camptothecins interfere with tumor growth. Although the clinical use of camptothecins has had a significant impact on cancer therapy, de novo or acquired clinical resistance to these drugs is common. Clinical resistance to camptothecins is still a poorly understood phenomenon, likely involving pharmacological and tumor-related factors. Experimental models including yeast and mammalian cell cultures suggest three general mechanisms of camptothecin resistance: i) reduced cellular accumulation of drugs, ii) alteration in the structure/expression of topoisomerase I, and iii) alterations in the cellular response to camptothecin-DNA-ternary complex formation. Some lines of evidence have also suggested links between cellular camptothecin resistance, the existence of a subset of tumor-initiating cells and miRNA deregulation. In this regard, a better definition of the molecular events clarifying the regulation of tumorigenesis and gene expression might contribute to gain insight into the molecular mechanisms on the basis of camptothecin resistance of tumors and to identify new molecular tools for targeting cancer cells. The relevance of these mechanisms to clinical drug resistance has not yet been completely defined, but their evaluation in clinical specimens should help to define personalized treatments including camptothecins as single agents or in combination with other cytotoxic and target-specific anticancer agents. The present review focuses on the cellular/ molecular aspects involved in resistance of tumor cells to camptothecins, including the potential role of cancer stem cells and deregulated miRNAs, and on the approaches proposed for overcoming resistance.

Using virtual reality to rehabilitate neglect.

PURPOSE: Virtual Reality (VR) platforms gained a lot of attention in the rehabilitation field due to their ability to engage patients and the opportunity they offer to use real world scenarios. As neglect is characterized by an impairment in exploring space that greatly affects daily living, VR could be a powerful tool compared to classical paper and pencil tasks and computer training. Nevertheless, available platforms are costly and obstructive. Here we describe a low cost platform for neglect rehabilitation, that using consumer equipments allows the patient to train at home in an intensive fashion. METHOD: We tested the platform on IB, a chronic neglect patient, who did not benefit from classical rehabilitation. RESULTS: Our results show that IB improved both in terms of neglect and attention. Importantly, these ameliorations lasted at a follow up evaluation 5 months after the last treatment session and generalized to everyday life activities. CONCLUSIONS: VR platforms built using equipment technology and following theoretical principles on brain functioning may induce greater ameliorations in visuo-spatial deficits than classical paradigms possibly thanks to the real world scenarios in association with the "visual feedback" of the patient's own body operating in the virtual environment.

Synthesis, characterization, DFT studies and catalytic activities of manganese(II) complex with 1,4-bis(2,2':6,2''-terpyridin-4'-yl) benzene.

A new di-manganese complex with "back-to-back" 1,4-bis(2,2':6,2''-terpyridin-4'-yl) benzene ligation has been synthesized and characterised by a variety of techniques. The back-to-back ligation presents a novel new mononuclear manganese catalytic centre that functions as a heterogeneous catalysis for the evolution of oxygen in the presence of an exogenous oxidant. We discuss the synthesis and spectroscopic characterizations of this complex and propose a mechanism for oxygen evolution activity of the compound in the presence of oxone. The di-manganese complex also shows efficient and selective catalytic oxidation of sulfides in the presence of H(2)O(2). Density functional theory calculations were used to assess the structural optimization of the complex and a proposed reaction pathway with oxone. The calculations show that middle benzene ring is distorted respect to both of metallic centers, and this in turn leads to negligible resonance of electrons between two sides of complex. The calculations also indicate the unpaired electron located on oxyl-ligand emphasizes the radical mechanism of water oxidation for the system.