A new perspective on vitamin B12 deficiency in rheumatology: a case-based review.

Vitamin B12 (cobalamin) deficiency is common in patients with rheumatic diseases. Pernicious anemia is a well-known cause, but recent reports suggest that autoimmune-derived deficiency may not be limited to this cause alone. Symptoms of low vitamin B12 concentration are often deceptive, mimicking and overlapping with symptoms of other conditions. Neuropsychiatric manifestations, anemia, and fatigue are frequently attributed to a rheumatic disease without further evaluation. In this study, we present three cases of patients with neuropathic pain, depression, fatigue, and muscle weakness, initially attributed to a rheumatic disease, which almost completely resolved after implementing vitamin B12 supplementation. Furthermore, we provide an overview of current scientific reports regarding the potential use of cobalamin in rheumatology. Treatment of pain and neuropathy, often very challenging in long-lasting rheumatic diseases, can be more effective after a course of vitamin B12, even when no apparent deficiency is detected in laboratory tests. Considering recent research demonstrating vitamin B12's nerve-protecting properties, we recommend that physicians should assess vitamin B12 levels early in the diagnostic process of rheumatic diseases. In specific cases, physicians should consider cobalamin supplementation regardless of vitamin B12 serum concentration.

Metabolomics in systemic sclerosis.

Systemic sclerosis is a rare autoimmune condition leading to incurable complications. Therefore fast and precise diagnosis is crucial to prevent patient death and to maintain quality of life. Unfortunately, currently known biomarkers do not meet this need. To address this problem researchers use diverse approaches to elucidate the underlying aberrations. One of the methods applied is metabolomics. This modern technique enables a comprehensive assessment of multiple compound concentrations simultaneously. As it has been gaining popularity, we found it necessary to summarize metabolomic studies presented so far in a narrative review. We found 11 appropriate articles. All of the researchers found significant differences between patients and control groups, whereas the reported findings were highly inconsistent. Additionally, we have found the investigated groups in most studies were scarcely described, and the inclusion/exclusion approach was diverse. Therefore, further study with meticulous patient assessment is necessary.

Co-existence of ANCA-associated vasculitides with immune-mediated diseases: a single-center observational study.

BACKGROUND: Antineutrophil cytoplasmic antibody-associated vasculitides (AAV) is a group of systemic necrotizing small vessel autoimmune diseases, with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) being the two most common. The co-existence of AAV with different immune-mediated diseases (autoimmune disesases - AID) might affect the clinical presentation of the primary disease. The purpose of the study was to assess the co-existence of AAV with AID and to investigate whether it affects the characteristics and the course of AAV. METHODS: A retrospective single-center study was performed to identify patients with a diagnosis of MPA or GPA and concomitant AID, and to investigate their clinical features and characteristics. The group consisted of consecutive unselected AAV patients treated at a large university-based hospital, since 1988 with follow-up until 2022. RESULTS: Among 284 patients diagnosed either with GPA (232) or MPA (52), 40 (14,1%) had co-existing AIDs. The most frequent were: Hashimoto thyroiditis (16 cases), rheumatoid arthritis (8 cases), followed by psoriasis (6 cases), pernicious anemia (3 cases), and alopecia (3 cases). Patients with autoimmune comorbidities had a significantly longer time between the onset of symptoms and the diagnosis (26 vs. 11 months, p < 0.001). Laryngeal involvement (20.0% vs. 9.0%, p = 0,05), peripheral nervous system disorders (35.0% vs. 13.9%, p < 0.001), and neoplasms (20.0% vs. 8.6%, p = 0,044) were more common in patients with AID comorbidities, compared to subjects without AID. In contrast, renal involvement (45.0% vs. 70.9%, p = 0.001) and nodular lung lesions (27.5% vs. 47.5%, p = 0.044) were significantly less frequent in patients with co-morbidities. Following EUVAS criteria, patients with autoimmune co-morbidities had a generalized form of the disease without organ involvement (52.5% vs. 27.2%, p = 0.007), while the others had a higher percentage of generalized form with organ involvement (38.3% vs. 20.0%, p = 0.007). CONCLUSIONS: The coexistence of AAV with different autoimmune diseases is not common, but it might affect the clinical course of the disease. Polyautoimmunity prolonged the time to diagnosis, but the AAV course seemed to be milder. Particular attention should be paid to the increased risk of cancer in these patients. It also seems reasonable that AAV patients should receive a serological screening to exclude the development of overlapping diseases.

Elevated concentration of beta2-microglobulin among patients with carpal tunnel syndrome in the course of primary Sjögren syndrome - a prospective observational study on 50 patients.

INTRODUCTION: Sjögren's syndrome (SS) is a chronic autoimmune disease characterized by lymphocytic infiltrates in the exocrine glands. Carpal tunnel syndrome (CTS) is suggested to be more frequent among SS patients than in the general population. The aim of this study was to seek associations between the CTS and the laboratory and clinical findings of SS patients. METHODS: Fifty patients diagnosed with primary SS (pSS) were examined. Clinical evaluation by a rheumatologist and electrophysiological studies were conducted. Data on laboratory tests results was collected. Control group consisted of 50 sex and age-matched individuals with osteoarthritis (OA). RESULTS: Out of 50 patients in the study group 27 (54%) were diagnosed with CTS. The prevalence of CTS among 50 individuals in the control group was 8%. Among pSS patients with CTS the joint involvement was not more common than in those from the non-CTS group [15 vs. 13 (p = 0.945)]. There was an expected difference in sleep disorders [18 vs. 9 (p = 0.012)] and paresthesia [23 vs. 13 (p = 0.024)]. The major finding was a significant difference in elevated beta2-microglobulin (B2MG) [23 vs. 13 (p = 0.024)]. Other studied factors, suggested in the literature as significant in the pSS-related neuropathy, were not statistically different between the groups. CONCLUSION: Our study confirms that CTS is more prevalent among pSS patients than in the general population and suggests that a new approach is required towards the pathogenesis of this phenomenon. We hypothesize that CTS is more associated with an overall disease activity than joint involvement as such.

The use of intravascular contrast media in patients with impaired kidney function - joint clinical practice position statement of the Polish Society of Nephrology and the Polish Medical Society of Radiology.

Radiological procedures utilising intravascular contrast media (ICM) are fundamental to modern medicine, enhancing diagnostics and treatment in diverse medical fields. However, the application of ICM has been constrained in patients with compromised kidney function due to perceived nephrotoxic risks, called contrast-induced nephropathy or contrastinduced acute kidney injury. Historical evidence marked ICM as a possible contributor to kidney damage. This led to restrictive guidelines advocating limited ICM use in patients with impaired renal function, preventing crucial radiographic interventions in patients with acute kidney injury (AKI) and chronic kidney disease. Recent advances challenge these traditional views. In particular, no direct causal relationship has been confirmed between contrast admi-nistration and elevated serum creatinine concentrations in humans. Furthermore, contemporary research models and meta-analyses do not associate AKI with contrast usage. This paper, prepared by a cross-disciplinary team of nephrologists and radiologists, presents updated guidelines for ICM application amid renal function impairments, emphasising the reduced nephrotoxic risks currently understood and loosening the previous restrictive approach in patients with renal dysfunction.

Dissecting transmembrane bicarbonate transport by 1,8-di(thio)amidocarbazoles.

Synthetic ionophores able to transport bicarbonate and chloride anions across lipid bilayers are appealing for their wide range of potential biological applications. We have studied the bicarbonate and chloride transport by carbazoles with two amido/thioamido groups using a bicarbonate-sensitive europium(III) probe in liposomes and found a highly remarkable transporter concentration dependence. This can be explained by a combination of two distinct transport mechanisms: HCO3-/Cl- exchange and a combination of unassisted CO2 diffusion and HCl transport, of which the respective contributions were quantified. The compounds studied were found to be highly potent HCl transporters. Based on the mechanistic insights on anion transport, we have tested the antimicrobial activity of these compounds and found a good correlation with their ion transport properties and a high activity against Gram-positive bacteria.

The Causes and Potential Injurious Effects of Elevated Serum Leptin Levels in Chronic Kidney Disease Patients.

Leptin is an adipokine that regulates appetite and body mass and has many other pleiotropic functions, including regulating kidney function. Increased evidence shows that chronic kidney disease (CKD) is associated with hyperleptinemia, but the reasons for this phenomenon are not fully understood. In this review, we focused on potential causes of hyperleptinemia in patients with CKD and the effects of elevated serum leptin levels on patient kidney function and cardiovascular risk. The available data indicate that the increased concentration of leptin in the blood of CKD patients may result from both decreased leptin elimination from the circulation by the kidneys (due to renal dysfunction) and increased leptin production by the adipose tissue. The overproduction of leptin by the adipose tissue could result from: (a) hyperinsulinemia; (b) chronic inflammation; and (c) significant lipid disturbances in CKD patients. Elevated leptin in CKD patients may further deteriorate kidney function and lead to increased cardiovascular risk.

Carbazole-Based Colorimetric Anion Sensors.

Owing to their strong carbazole chromophore and fluorophore, as well as to their powerful and convergent hydrogen bond donors, 1,8-diaminocarbazoles are amongst the most attractive and synthetically versatile building blocks for the construction of anion receptors, sensors, and transporters. Aiming to develop carbazole-based colorimetric anion sensors, herein we describe the synthesis of 1,8-diaminocarbazoles substituted with strongly electron-withdrawing substituents, i.e., 3,6-dicyano and 3,6-dinitro. Both of these precursors were subsequently converted into model diamide receptors. Anion binding studies revealed that the new receptors exhibited significantly enhanced anion affinities, but also significantly increased acidities. We also found that rear substitution of 1,8-diamidocarbazole with two nitro groups shifted its absorption spectrum into the visible region and converted the receptor into a colorimetric anion sensor. The new sensor displayed vivid color and fluorescence changes upon addition of basic anions in wet dimethyl sulfoxide, but it was poorly selective; because of its enhanced acidity, the dominant receptor-anion interaction for most anions was proton transfer and, accordingly, similar changes in color were observed for all basic anions. The highly acidic and strongly binding receptors developed in this study may be applicable in organocatalysis or in pH-switchable anion transport through lipophilic membranes.

Isoreticular Linker Substitution in Conductive Metal-Organic Frameworks with Through-Space Transport Pathways.

The extension of reticular chemistry concepts to electrically conductive three-dimensional metal-organic frameworks (MOFs) has been challenging, particularly for cases in which strong interactions between electroactive linkers create the charge transport pathways. Here, we report the successful replacement of tetrathiafulvalene (TTF) with a nickel glyoximate core in a family of isostructural conductive MOFs with Mn2+ , Zn2+ , and Cd2+ . Different coordination environments of the framework metals lead to variations in the linker stacking geometries and optical properties. Single-crystal conductivity data are consistent with charge transport along the linker stacking direction, with conductivity values only slightly lower than those reported for the analogous TTF materials. These results serve as a case study demonstrating how reticular chemistry design principles can be extended to conductive frameworks with significant intermolecular contacts.

Alterations of Fatty Acid Profile May Contribute to Dyslipidemia in Chronic Kidney Disease by Influencing Hepatocyte Metabolism.

Chronic kidney disease (CKD) is associated with atherogenic dyslipidemia. Our aim was firstly to investigate patterns of fatty acids (FA) composition through various stages of CKD, and secondly, to evaluate the effect of CKD-specific FA disturbances on the expression of genes related to lipid metabolism at a cellular level. Serum FA composition was analyzed in 191 patients with consecutive severity stages of CKD, and 30 healthy controls free from CKD. Next, HepG2 human hepatic cells were treated with major representatives of various FA groups, as well as with FA extracted from a mix of serums of controls and of CKD stage 5 patients. Across worsening stages of CKD severity, there was an increasing monounsaturated FA (MUFA) content. It was associated with a concomitant decrease in n-3 and n-6 polyunsaturated FA. The incubation of hepatocytes with FA from CKD patients (compared to that of healthy subjects), resulted in significantly higher mRNA levels of genes involved in FA synthesis (fatty acid synthase (FASN) increased 13.7 ± 3.5 times, stearoyl-CoA desaturase 1 (SCD1) increased 4.26 ± 0.36 times), and very low density lipoprotein (VLDL) formation (apolipoprotein B (ApoB) increased 7.35 ± 1.5 times, microsomal triacylglycerol transfer protein (MTTP) increased 2.74 ± 0.43 times). In conclusion, there were progressive alterations in serum FA composition of patients with CKD. These alterations may partly contribute to CKD hypertriglyceridemia by influencing hepatocyte expression of genes of lipid synthesis and release.

A Photoswitchable Heteroditopic Ion-Pair Receptor.

Designing light-switchable heteroditopic receptors is challenging because it necessitates simultaneous (de)activation of two separate binding sites. Herein, we present the first photoswitchable heteroditopic ion-pair receptor in which both cation and anion binding sites are simultaneously and reversibly switched OFF and ON by a single photoswitch. Our receptor is simple, low molecular weight, and readily synthesized from commercially available precursors. Single-crystal X-ray structures and NMR spectroscopic titrations support ion-pair binding to the receptor both in the solid state and in solution, with strong positive cooperativity between the cation and anion binding. The receptor can be completely switched OFF by UV light-triggered photoisomerization of an acylhydrazone C═N double bond and remains kinetically stable in the deactivated form due to an intramolecular hydrogen bond. Its re-activation could be achieved by light irradiation or, more effectively, by fast acid-catalyzed back-isomerization. Our simple photoswitchable ion-pair receptor may serve as a blueprint for the design of new generations of switchable receptors, transporters, soft materials, and self-assembled systems, where incorporation of a functional heteroditopic ON/OFF photoswitch has been challenging up to now.

1,8-Diamidocarbazoles: an easily tuneable family of fluorescent anion sensors and transporters.

The synthesis, structure and anion recognition properties of an extensive, rationally designed series of bisamide derivatives of 1,8-diaminocarbazole and 1,8-diamino-3,6-dichlorocarbazole are described. Despite simple structures and the presence of only three hydrogen bond donors, such compounds are remarkably strong and selective receptors for oxyanions in DMSO + 0.5%H2O. Owing to their carbazole fluorophore, they are also sensitive turn-on fluorescent sensors for H2PO4- and AcO-, with a more than 15-fold increase in fluorescence intensity upon binding. Despite relatively weak chloride affinity, some of the diamidocarbazoles have also been shown, for the first time, to be very active chloride transporters through lipid bilayers. The binding, sensing and transport properties of these receptors can be easily modulated by the usually overlooked variations in the length and degree of branching of their alkyl side arms. Overall, this study demonstrates that the 1,8-diamidocarbazole binding unit is a very promising and synthetically versatile platform for the development of fluorescent sensors and transporters for anions.

Global Prevalence of Protein-Energy Wasting in Kidney Disease: A Meta-analysis of Contemporary Observational Studies From the International Society of Renal Nutrition and Metabolism.

OBJECTIVE: To better define the prevalence of protein-energy wasting (PEW) in kidney disease is poorly defined. METHODS: We performed a meta-analysis of PEW prevalence from contemporary studies including more than 50 subjects with kidney disease, published during 2000-2014 and reporting on PEW prevalence by subjective global assessment or malnutrition-inflammation score. Data were reviewed throughout different strata: (1) acute kidney injury (AKI), (2) pediatric chronic kidney disease (CKD), (3) nondialyzed CKD 3-5, (4) maintenance dialysis, and (5) subjects undergoing kidney transplantation (Tx). Sample size, period of publication, reporting quality, methods, dialysis technique, country, geographical region, and gross national income were a priori considered factors influencing between-study variability. RESULTS: Two studies including 189 AKI patients reported a PEW prevalence of 60% and 82%. Five studies including 1776 patients with CKD stages 3-5 reported PEW prevalence ranging from 11% to 54%. Finally, 90 studies from 34 countries including 16,434 patients on maintenance dialysis were identified. The 25th-75th percentiles range in PEW prevalence among dialysis studies was 28-54%. Large variation in PEW prevalence across studies remained even when accounting for moderators. Mixed-effects meta-regression identified geographical region as the only significant moderator explaining 23% of the observed data heterogeneity. Finally, two studies including 1067 Tx patients reported a PEW prevalence of 28% and 52%, and no studies recruiting pediatric CKD patients were identified. CONCLUSION: By providing evidence-based ranges of PEW prevalence, we conclude that PEW is a common phenomenon across the spectrum of AKI and CKD. This, together with the well-documented impact of PEW on patient outcomes, justifies the need for increased medical attention.

Hyper-Elongation in Colorectal Cancer Tissue - Cerotic Acid is a Potential Novel Serum Metabolic Marker of Colorectal Malignancies.

BACKGROUNDS/AIMS: Colorectal cancer (CRC) cells show some alterations of lipid metabolism. Elongation of fatty acids (FA) has not been studied in CRC tissues thus far. The aim of this study was to verify if CRC specimens and normal colon mucosa differ in terms of their levels of very long-chain FAs, a product of FA elongation. Moreover, the expression of elongase genes has been studied in normal tissue and CRC. Finally, we searched for some specific products of FA elongation in serum of CRC patients. METHODS: The specimens of normal colon mucosa and CRC were obtained from nineteen CRC patients differ in terms of FA elongation. We also searched for some specific products of FA elongation in serum of CRC patients and from healthy volunteers. Tissue and serum FA profiles were determined by means of gas chromatography-mass spectrometry (GC/MS), and the tissue expression of elongases (ELOVLs) was analyzed with real-time PCR. RESULTS: Compared to normal colon tissue, CRC specimens showed significantly higher levels of 22-, 24- and 26-carbon FAs, stronger expressions of ELOVL1 and ELOVL6 (4- and 9-fold elevated respectively), and higher values of 18: 0/16: 0 elongation index. We also demonstrated presence of cerotic acid (26: 0) in serum of all CRC patients but in none of the healthy controls. CONCLUSIONS: CRC tissue seems to be characterized by enhanced FA elongation (hyper-elongation). Presence of cerotic acid in CRC patients sera and absence of this FA in healthy subjects points to this compound as a strong candidate for specific metabolic marker of colorectal malignancies.

Selective turn-on fluorescence sensing of sulfate in aqueous-organic mixtures by an uncharged bis(diamidocarbazole) receptor.

A linear, uncharged, hydrogen bonding receptor A with two carbazole-based binding domains was synthesised and evaluated for its anion binding properties in DMSO/H2O mixtures. 1H NMR titrations revealed that, in DMSO/H2O 0.5%, A forms both 1 : 1 and 1 : 2 complexes with SO42-, H2PO4-, PhCOO- and Cl-. In 1 : 1 complexes the receptor encloses the tetrahedral anions tightly, forming a helical structure, while Cl- binds with a single carbazole unit only. In the presence of 10% of water the 1 : 2 complexes with SO42- and PhCOO- disappear, and the respective 1 : 1 binding constants decrease sufficiently to be quantified by UV-Vis titration. In this highly competitive medium, A binds sulfate with K1:1 = 105.47 M-1, i.e., it binds approx. 30, 360 and >1000 times more strongly than H2PO4-, PhCOO- and Cl-, respectively. Furthermore, the association with sulfate is over 50 times stronger than that for a model diamidocarbazole 1 under identical conditions, suggesting a very strong chelating effect due to the diglycoyl linker. Increasing the amount of water to 25% (the solubility limit of A) lowers the 1 : 1 binding constant with SO42- to 103.73 M-1. Receptor A was shown to act as a selective turn-on fluorescent sensor for sulfate, able to sense sulfate in sulfate-rich mineral water.

Suitability of selected chromatographic columns for analysis of fatty acids in dialyzed patients.

Gas chromatography-mass spectrometry is a preferred method for fatty acid (FA) analysis in biofluids from patients with metabolic diseases. Complex characteristics of FAs make their analysis particularly challenging. Selection of an appropriate chromatographic column is particularly important component of the process as it provides optimal separation and detection of possibly all FAs present in the sample. However, no accurate protocol for comparative evaluation of capillary columns for the analysis of whole serum FA profile in patients with chronic kidney disease (CKD) has been developed thus far. Therefore, in the present study four columns were examined to select the one providing optimal separation and determination of FA profiles in this group of patients. Moreover, serum FA profiles obtained with the selected column in CKD patients subjected to peritoneal dialysis and healthy controls were compared. Thirty-seven component FAME Mix and sera from CKD patients were used to optimize chromatographic conditions and to select the most appropriate column. The ZB-5 column turned out to be the most appropriate for the analysis of whole FA profile in CKD patients' sera. Then, this column was used to compare FA profiles in patients subjected to peritoneal dialysis and in healthy controls. The analysis demonstrated many abnormalities in the FA profile of CKD patients. Further studies involving larger groups of patients presenting with other stages of CKD are required to explain the impact of the disease progression on composition of serum FAs.

Disorders of serum omega-3 fatty acid composition in dialyzed patients, and their associations with fat mass.

Patients with chronic kidney disease (CKD) are at increased risk of cardiovascular mortality. Lipid disorders, a constant feature of CKD, might contribute to this state. The aim of this study was to evaluate n-3 polyunsaturated fatty acids (PUFA) composition in CKD patients treated with dialysis, in comparison to the general population and to assess possible associations between the n-3 PUFA profile and anthropometric variables. Thirty-three prevalent dialysis patients were studied and compared with an age- and sex-adjusted control group of 22 patients. Fatty acid composition in serum was analyzed by gas chromatography with a mass spectrometer detector (GC-MS) and anthropometric measures were assessed by bioimpedance spectroscopy. The fatty acid profile of dialyzed patients was characterized by a significantly lower percentage content of n-3 PUFA. For α-linolenic acid (ALA), it was 0.21 ± 0.09% in dialysis patients versus 0.33 ± 0.11% in the control group (p < .001). For eicosapentanoic acid (EPA), 0.59 ± 0.23% versus 1.15 ± 0.87% (p < .001), and for docosahexaenoic acid (DHA) 1.11 ± 0.50% versus 1.75 ± 0.87% (p < .001), respectively. The amount of n-3 PUFA decreased with time on dialysis and it correlated positively with body fat mass. For DHA, this correlation was r = .48 (p < .01) and for EPA r = .40 (p < .05). Patients with CKD have a relatively low content of n-3 PUFA which may contribute to their high cardiovascular risk. Patients with a higher content of body fat are characterized by a favorable fatty acid composition.

Multivalency by self-assembly: binding of concanavalin†A to metallosupramolecular architectures decorated with multiple carbohydrate groups.

Multiplication of functional units through self-assembly is a powerful way to new properties and functions. In particular, self-organization of components decorated with recognition groups leads to multivalent entities, amenable to strong and selective binding with multivalent targets, such as protein receptors. Here we describe an efficient, supramolecular, one-pot valency multiplication process proceeding through self-organization of monovalent components into well-defined, grid-shaped [2×2] tetranuclear complexes bearing eight sugar residues for multivalent interaction with the tetrameric lectin, concanavalin A (Con A). The grids are stable in water under physiological pH at a relatively high concentration, but dissociate readily at slightly more acidic pH or upon dilution below a certain threshold, in a type of on-off behavior. The carbohydrate-decorated grids interact strongly and selectively with Con A forming triply supramolecular bio-hybrid polymeric networks, which lead to a highly specific phase-separation and quasi-quantitative precipitation of Con A out of solution. Dramatic effects of valency number on agglutination properties were demonstrated by comparison of grids with divalent carbohydrates of covalent and non-covalent (L-shaped, mononuclear zinc complex) scaffolds. The results presented here provide prototypical illustration of the power of multivalency generation by self-assembly leading to defined arrays of functional groups and binding patterns.

Anion-templated synthesis of a switchable fluorescent [2]catenane with sulfate sensing capability.

Anion templation strategies have facilitated the synthesis of various catenane and rotaxane hosts capable of strong and selective binding of anions in competitive solvents. However, this approach has primarily relied on positively charged precursors, limiting the structural diversity and the range of potential applications of the anion-templated mechanically interlocked molecules. Here we demonstrate the synthesis of a rare electroneutral [2]catenane using a powerful, doubly charged sulfate template and a complementary diamidocarbazole-based hydrogen bonding precursor. Owing to the unique three-dimensional hydrogen bonding cavity and the embedded carbazole fluorophores, the resulting catenane receptor functions as a sensitive fluorescent turn-ON sensor for the highly hydrophilic sulfate, even in the presence of a large excess of water. Importantly, the [2]catenane exhibits enhanced binding affinity and selectivity for sulfate over its parent macrocycle and other acyclic diamidocarbazole-based receptors. We demonstrate also, for the first time, that the co-conformation of the catenane may be controlled by reversible acid/base induced protonation and deprotonation of the anionic template, SO42-. This approach pioneers a new strategy to induce molecular motion of interlocked components using switchable anionic templates.

Vitamin B12 and a metal-organic framework enable the photocatalytic generation of alkyl radicals.

A versatile Co-catalyst-vitamin B12 (cobalamin)-can be photochemically reduced to its catalytically active Co(I) form under visible light irradiation, in the presence of MIL-125-NH2(Ti) as a photocatalyst and utilized for the generation of alkyl radicals. The prior reduction of cobalamin to the Co(II) form is not required in this method.