A novel palladium complex with a coumarin-thiosemicarbazone hybrid ligand inhibits Trypanosoma cruzi release from host cells and lowers the parasitemia in vivo.

In this work, two analogous coumarin-thio and semicarbazone hybrid compounds were prepared and evaluated as a potential antichagasic agents. Furthermore, palladium and platinum complexes with the thiosemicarbazone derivative as ligand (L1) were obtained in order to establish the effect of metal complexation on the antiparasitic activity. All compounds were fully characterized both in solution and in solid state including the resolution of the crystal structure of the palladium complex by X-ray diffraction methods. Unexpectedly, all experimental and theoretical characterizations in the solid state, demonstrated that the obtained palladium and platinum complexes are structurally different: [PdCl(L1)] and [PtCl2(HL1)]. All the studied compounds lower the proliferation of the amastigote form of Trypanosoma cruzi while some of them also have an effect on the trypomastigote stage. Additionally, the compounds inhibit T. cruzi release from host cells in variable extents. The Pd compound presented a remarkable profile in all the in vitro experiments, and it showed no toxicity for mammalian cells in the assayed concentrations. In this sense, in vivo experiments were performed for this compound using an acute model of Chagas disease. Results showed that the complex significantly lowered the parasite count in the mice blood with no significant toxicity.

Diarrhea secondary to intestinal infiltration secondary to renal epidermoid carcinoma.

Renal squamous cell carcinoma is a rare neoplasm in adults, but with an aggressive behavior. It is diagnosed in most cases in advanced stages. The invasion of the digestive tract by this type of tumor is rare, due to the anatomical arrangement of the colon, however, when it occurs, it carries a poor prognosis for the patient. Digestive endoscopy allows us to reach a definitive diagnosis since these patients usually present digestive manifestations, such as diarrhoea, digestive bleeding or abdominal pain.

Multi-target heteroleptic palladium bisphosphonate complexes.

Bisphosphonates are the most commonly prescribed drugs for the treatment of osteoporosis and other bone illnesses. Some of them have also shown antiparasitic activity. In search of improving the pharmacological profile of commercial bisphosphonates, our group had previously developed first row transition metal complexes with N-containing bisphosphonates (NBPs). In this work, we extended our studies to heteroleptic palladium-NBP complexes including DNA intercalating polypyridyl co-ligands (NN) with the aim of obtaining potential multi-target species. Complexes of the formula [Pd(NBP)2(NN)]·2NaCl·xH2O with NBP = alendronate (ale) or pamidronate (pam) and NN = 1,10 phenanthroline (phen) or 2,2'-bipyridine (bpy) were synthesized and fully characterized. All the obtained compounds were much more active in vitro against T. cruzi (amastigote form) than the corresponding NBP ligands. In addition, complexes were nontoxic to mammalian cells up to 50-100 µM. Compounds with phen as ligand were 15 times more active than their bpy analogous. Related to the potential mechanism of action, all complexes were potent inhibitors of two parasitic enzymes of the isoprenoid biosynthetic pathway. No correlation between the anti-T. cruzi activity and the enzymatic inhibition results was observed. On the contrary, the high antiparasitic activity of phen-containing complexes could be related to their ability to interact with DNA in an intercalative-like mode. These rationally designed compounds are good candidates for further studies and good leaders for future drug developments. Four new palladium heteroleptic complexes with N-containing commercial bisphosphonates and DNA intercalating polypyridyl co-ligands were synthesized and fully characterized. All complexes displayed high anti-T. cruzi activity which could be related to the inhibition of the parasitic farnesyl diphosphate synthase enzyme but mainly to their ability to interact DNA.

Interaction with Blood Proteins of a Ruthenium(II) Nitrofuryl Semicarbazone Complex: Effect on the Antitumoral Activity.

The steady rise in the cancer burden and grim statistics set a vital need for new therapeutic solutions. Given their high efficiency, metallodrugs are quite appealing in cancer chemotherapy. This work examined the anticancer activity of an anti-trypanosomal ruthenium-based compound bearing the 5-nitrofuryl pharmacophore, [RuII(dmso)2(5-nitro-2-furaldehyde semicarbazone)] (abbreviated as RuNTF; dmso is the dimethyl sulfoxide ligand). The cytotoxicity of RuNTF was evaluated in vitro against ovarian adenocarcinoma, hormone-dependent breast adenocarcinoma, prostate carcinoma (grade IV) and V79 lung fibroblasts human cells. The activity of RuNTF was similar to the benchmark metallodrug cisplatin for the breast line and inactive against the prostate line and lung fibroblasts. Given the known role of serum protein binding in drug bioavailability and the distribution via blood plasma, this study assessed the interaction of RuNTF with human serum albumin (HSA) by circular dichroism (CD) and fluorescence spectroscopy. The fluorescence emission quenching from the HSA-Trp214 residue and the lifetime data upon RuNTF binding evidenced the formation of a 1:1 {RuNTF-albumin} adduct with log Ksv = (4.58 ± 0.01) and log KB = (4.55 ± 0.01). This is supported by CD data with an induced CD broad band observed at ~450 nm even after short incubation times. Importantly, the binding to either HSA or human apo-transferrin is beneficial to the cytotoxicity of the complex towards human cancer cells by enhancing the cytotoxic activity of RuNTF.

Ibandronate metal complexes: solution behavior and antiparasitic activity.

To face the high costs of developing new drugs, researchers in both industry and academy are looking for ways to repurpose old drugs for new uses. In this sense, bisphosphonates that are clinically used for bone diseases have been studied as agents against Trypanosoma cruzi, causative parasite of Chagas disease. In this work, the development of first row transition metal complexes (M = Co2+, Mn2+, Ni2+) with the bisphosphonate ibandronate (iba, H4iba representing the neutral form) is presented. The in-solution behavior of the systems containing iba and the selected 3d metal ions was studied by potentiometry. Mononuclear complexes [M(Hxiba)](2-x)- (x = 0-3) and [M(Hiba)2]4- together with the formation of the neutral polynuclear species [M2iba] and [M3(Hiba)2] were detected for all studied systems. In the solid state, complexes of the formula [M3(Hiba)2(H2O)4]·6H2O were obtained and characterized. All obtained complexes, forming [M(Hiba)]- species under the conditions of the biological studies, were more active against the amastigote form of T. cruzi than the free iba, showing no toxicity in mammalian Vero cells. In addition, the same complexes were selective inhibitors of the parasitic farnesyl diphosphate synthase (FPPS) enzyme showing poor inhibition of the human one. However, the increase of the anti-T. cruzi activity upon coordination could not be explained neither through the inhibition of TcFPPS nor through the inhibition of TcSPPS (T. cruzi solanesyl-diphosphate synthase). The ability of the obtained metal complexes of catalyzing the generation of free radical species in the parasite could explain the observed anti-T. cruzi activity.

Adjustments, extinction, and remains of selenocysteine incorporation machinery in the nematode lineage.

Selenocysteine (Sec) is encoded by an UGA codon with the help of a SECIS element present in selenoprotein mRNAs. SECIS-binding protein (SBP2/SCBP-2) mediates Sec insertion, but the roles of its domains and the impact of its deficiency on Sec insertion are not fully understood. We used Caenorhabditis elegans to examine SBP2 function since it possesses a single selenoprotein, thioredoxin reductase-1 (TRXR-1). All SBP2 described so far have an RNA-binding domain (RBD) and a Sec-incorporation domain (SID). Surprisingly, C. elegans SBP2 lacks SID and consists only of an RBD. An sbp2 deletion mutant strain ablated Sec incorporation demonstrating SBP2 essentiality for Sec incorporation. Further in silico analyses of nematode genomes revealed conservation of SBP2 lacking SID and maintenance of Sec incorporation linked to TRXR-1. Remarkably, parasitic plant nematodes lost the ability to incorporate Sec, but retained SecP43, a gene associated with Sec incorporation. Interestingly, both selenophosphate synthetase (SPS) genes are absent in plant parasitic nematodes, while only Cys-containing SPS2 is present in Sec-incorporating nematodes. Our results indicate that C. elegans and the nematode lineage provide key insights into Sec incorporation and the evolution of Sec utilization trait, selenoproteomes, selenoproteins, and Sec residues. Finally, our study provides evidence of noncanonical translation initiation in C. elegans, not previously known for this well-established animal model.

Cancer risk with biologic and targeted synthetic DMARDs in patients with rheumatic diseases and previous malignancies: Results from the BIOBADASER register.

OBJECTIVE: to investigate the occurrence and relative risk of incident malignancy in patients with rheumatic diseases and previous malignancies treated with biologic and targeted synthetic DMARDs (b/tsDMARDs). METHODS: Cohort study of patients included in BIOBADASER 3.0 up to 2021, treated with b/tsDMARDs and history of a previous malignancy. Incident cancer was defined as any cancer (new primary, local recurrence or metastases) during the drug exposure. Incidence rate ratios of cancer per 1,000 patients-year (PY) and 95 % confidence interval (CI) were estimated. Rates of incident cancer in tsDMARDs and other bDMARDs versus TNFi were compared. RESULTS: A total of 352 patients from over 9,129 patients recorded in BIOBADASER 3.0 had a history of a previous malignancy. Overall, there were 47 incident malignancies (28 solid cancers, 18 non-melanoma skin cancers and 1 melanoma). The overall rate of incident malignancy was 47.4 (95 % CI 35.6-63.1) events/1,000 PY, ranging between 24.5 events/1000 PY in the anti-CD20 group to 93 events/1000 PY in the anti-CTLA-4 group. We did not find differences in the adjusted rate of incident cancer in patients exposed to JAKi [0.5 (95 % CI 0.2-1.7)], anti-CD20 [0.4(95 % CI 0.1-1)], or anti-IL6 [1.1(95 % CI 0.5-2.4)], anti-CTLA-4 [1.5 (95 % CI 0.7-3.1) or anti-IL17 [0.7 (95 % CI 0.2-2.4) versus TNFi therapy. CONCLUSIONS: We did not find differences in the risk of incident cancer in patients with rheumatic diseases and a previous malignancy between TNFi and other b/tsDMARDs. While incident cancers in our cohort were limited, our data is reassuring, awaiting validation in future studies.

Selenosemicarbazone Metal Complexes as Potential Metal-based Drugs.

The discovery of the anticancer activity of cisplatin has marked the emergence of modern Inorganic Medicinal Chemistry. This field of research is concerned with the application of inorganic compounds to therapy or diagnosis of disease. In particular, metal coordination of bioactive ligands has gained recognition in drug design. The interaction between transition metal ions and the organic drugs could enhance their diagnostic and therapeutic potentials by improving the stability and/or bioavailability or by achieving a metal-drug synergism through a dual or multiple mechanisms of action. The isosteric replacement of sulfur by selenium in thiosemicarbazones leads to selenosemicarbazones. This class of compounds exhibits numerous biological activities like antitumor, antimicrobial, antiviral, etc. and, in most cases, they were more pronounced in comparison to the sulfur analogues. On the other hand, while the effect of transition metal complexation on the biological activity of thiosemicarbazones has been widely studied, the pharmacological activity of the corresponding metal-selenosemicarbazone compounds has been less explored. In this work, the most relevant results related to the selenosemicarbazone metal complexes as potential metal-based drugs have been reviewed.

5-Nitrofuryl-Containing Thiosemicarbazone Gold(I) Compounds: Synthesis, Stability Studies, and Anticancer Activity.

This work describes the synthesis of four gold(I) [AuClL] compounds containing chloro and biologically active protonated thiosemicarbazones based on 5-nitrofuryl (L=HSTC). The stability of the compounds in dichloromethane, DMSO, and DMSO/culture media solutions was investigated by spectroscopy, cyclic voltammetry, and conductimetry, indicating the formation overtime of cationic monometallic [Au(HTSC)(DMSO)]± or [Au(HTSC)2 ]± , and/or dimeric species. Neutral [{Au(TSC)}2 ] species were obtained from one of the compounds in dichlomethane/n-hexane solution and characterized by X-ray crystallography revealing a Au-Au bond, and deprotonated thiosemicarbazone (TSC). The cytotoxicity of the gold compounds and thiosemicarbazone ligands was evaluated against selected cancer cell lines and compared to that of Auranofin. Studies of the most stable, cytotoxic, and selective compound on a renal cancer cell line (Caki-1) demonstrated its relevant antimigratory and anti-angiogenic properties, and preferential accumulation in the cell nuclei. Its mode of action seems to involve interaction with DNA, and subsequent cell death via apoptosis.

5-Nitrofuryl-Containing Thiosemicarbazone Gold(I) Compounds: Synthesis, Stability Studies, and Anticancer Activity.

Invited for this month's cover are the collaborating groups of Esteban Rodríguez-Arce from the University of Chile and María Contel from The City University of New York Brooklyn College. The cover picture shows "Supergold" a very powerful gender neutral warrior with superpowers who fights against cancer! The warrior's golden armor and sword represent the pharmacological power of the gold atom. Engraved on the shield, the gold-thiosemicarbazone molecules are the warrior's coat of arms. Supergold selectively destroys different cancer cells. More information can be found in the Research Article by Esteban Rodríguez-Arce, María Contel, and co-workers.

Copper(I)-Thiosemicarbazone Complexes with Dual Anticancer and Antiparasitic Activity.

Four new Cu(I) complexes of the general formula [Cu(PP)(LL)][BF4 ], in which PP is a phosphane ligand (triphenylphosphane or 1,2-bis(diphenylphosphano)ethane (dppe)) and LL is a bioactive thiosemicarbazone ligand (4-(methyl)-1-(5-nitrofurfurylidene)thiosemicarbazone) or 4-(ethyl)-1-(5-nitrofurfurylidene)thiosemicarbazone) were synthesized and fully characterized by classical analytical and spectroscopic methods. The anti-trypanosome and anticancer activities were investigated in vitro on Trypanosoma cruzi and in two human cancer cell lines (ovarian OVCAR3 and prostate PC3). To test the selectivity toward parasites and cancer cells, the cytotoxicity on normal monkey kidney VERO and human dermal fibroblasts HDF cells was also evaluated. The new heteroleptic complexes were more cytotoxic on T. cruzi and chemoresistant prostate PC3 cells than the benchmark drugs nifurtimox and cisplatin. The compounds also showed a high level of cellular internalization by the OVCAR3 cells and, in particular, those containing the dppe phosphane showed activation of the cell death mechanism via apoptosis. On the other hand, the production of reactive oxygen species induced by these complexes was not evident.

Juvenile idiopathic arthritis in the young adult. Methodology, objectives, and initial data from the JUVENSER registry.

OBJECTIVES: To describe the methodology, objectives, and initial data of the registry of young adult patients diagnosed with Juvenile Idiopathic Arthritis (JIA), JUVENSER. The main objective of the project is to know the sociodemographic and clinical characteristics, and disease activity of patients with JIA reaching the transition to adulthood. MATERIAL AND METHOD: Longitudinal, prospective, multicentre study, including patients between 16 and 25 years old, with a diagnosis of JIA in any of its categories. The main objective is to determine the characteristics and activity of JIA in the young adult. It includes sociodemographic variables, clinical variables, disease activity and joint damage rates, data on the use of health resources, and treatments used. The total duration of the project will be 3 years. A cohort of 534 young adult patients was obtained. CONCLUSIONS: The JUVENSER registry will constitute a cohort of young adults with JIA, which will allow the evaluation of the clinical characteristics and response to treatment of patients with disease onset in childhood, moving to adult clinics.

Facing Diseases Caused by Trypanosomatid Parasites: Rational Design of Pd and Pt Complexes With Bioactive Ligands.

Human African Trypanosomiasis (HAT), Chagas disease or American Trypanosomiasis (CD), and leishmaniases are protozoan infections produced by trypanosomatid parasites belonging to the kinetoplastid order and they constitute an urgent global health problem. In fact, there is an urgent need of more efficient and less toxic chemotherapy for these diseases. Medicinal inorganic chemistry currently offers an attractive option for the rational design of new drugs and, in particular, antiparasitic ones. In this sense, one of the main strategies for the design of metal-based antiparasitic compounds has been the coordination of an organic ligand with known or potential biological activity, to a metal centre or an organometallic core. Classical metal coordination complexes or organometallic compounds could be designed as multifunctional agents joining, in a single molecule, different chemical species that could affect different parasitic targets. This review is focused on the rational design of palladium(II) and platinum(II) compounds with bioactive ligands as prospective drugs against trypanosomatid parasites that has been conducted by our group during the last 20 years.

Thioredoxin and glutathione systems differ in parasitic and free-living platyhelminths.

BACKGROUND: The thioredoxin and/or glutathione pathways occur in all organisms. They provide electrons for deoxyribonucleotide synthesis, function as antioxidant defenses, in detoxification, Fe/S biogenesis and participate in a variety of cellular processes. In contrast to their mammalian hosts, platyhelminth (flatworm) parasites studied so far, lack conventional thioredoxin and glutathione systems. Instead, they possess a linked thioredoxin-glutathione system with the selenocysteine-containing enzyme thioredoxin glutathione reductase (TGR) as the single redox hub that controls the overall redox homeostasis. TGR has been recently validated as a drug target for schistosomiasis and new drug leads targeting TGR have recently been identified for these platyhelminth infections that affect more than 200 million people and for which a single drug is currently available. Little is known regarding the genomic structure of flatworm TGRs, the expression of TGR variants and whether the absence of conventional thioredoxin and glutathione systems is a signature of the entire platyhelminth phylum. RESULTS: We examine platyhelminth genomes and transcriptomes and find that all platyhelminth parasites (from classes Cestoda and Trematoda) conform to a biochemical scenario involving, exclusively, a selenium-dependent linked thioredoxin-glutathione system having TGR as a central redox hub. In contrast, the free-living platyhelminth Schmidtea mediterranea (Class Turbellaria) possesses conventional and linked thioredoxin and glutathione systems. We identify TGR variants in Schistosoma spp. derived from a single gene, and demonstrate their expression. We also provide experimental evidence that alternative initiation of transcription and alternative transcript processing contribute to the generation of TGR variants in platyhelminth parasites. CONCLUSIONS: Our results indicate that thioredoxin and glutathione pathways differ in parasitic and free-living flatworms and that canonical enzymes were specifically lost in the parasitic lineage. Platyhelminth parasites possess a unique and simplified redox system for diverse essential processes, and thus TGR is an excellent drug target for platyhelminth infections. Inhibition of the central redox wire hub would lead to overall disruption of redox homeostasis and disable DNA synthesis.

Complex I and II Subunit Gene Duplications Provide Increased Fitness to Worms.

Helminths use an alternative mitochondrial electron transport chain (ETC) under hypoxic conditions, such as those found in the gastrointestinal tract. In this alternative ETC, fumarate is the final electron acceptor and rhodoquinone (RQ) serves as an electron carrier. RQ receives electrons from reduced nicotinamide adenine dinucleotide through complex I and donates electrons to fumarate through complex II. In this latter reaction, complex II functions in the opposite direction to the conventional ETC (i.e., as fumarate reductase instead of succinate dehydrogenase). Studies in Ascaris suum indicate that this is possible due to changes in complex II, involving alternative succinate dehydrogenase (SDH) subunits SDHA and SDHD, derived from duplicated genes. We analyzed helminth genomes and found that distinct lineages have different gene duplications of complex II subunits (SDHA, SDHB, SDHC, and SDHD). Similarly, we found lineage-specific duplications in genes encoding complex I subunits that interact with quinones (NDUF2 and NDUF7). The phylogenetic analysis of ETC subunits revealed a complex history with independent evolutionary events involving gene duplications and losses. Our results indicated that there is not a common evolutionary event related to ETC subunit genes linked to RQ. The free-living nematode Caenorhabditis elegans uses RQ and has two genes encoding SDHA (sdha-1 and sdha-2) and two genes encoding NDUF2 (nduf2-1 and nduf2-2). sdha-1 and nduf2-1 are essential genes and have a similar expression pattern during C. elegans lifecycle. Using knockout strains, we found that sdha-2 and nduf2-2 are not essential, even in hypoxia. Yet, sdha-2 and nduf2-2 expression is increased in the early embryo and in dauer larvae, stages where there is low oxygen tension. Strikingly, sdha-1 and sdha-2 as well as nduf2-1 and nduf2-2 showed inverted expression profiles during the C. elegans life cycle. Finally, we found that sdha-2 and nduf2-2 knockout mutant strain progeny is affected. Our results indicate that different complex I and II subunit gene duplications provide increased fitness to worms.

New heterobimetallic ferrocenyl derivatives are promising antitrypanosomal agents.

In the search for a more effective chemotherapy for the treatment of Chagas' disease and human African trypanosomiasis, caused by Trypanosoma cruzi and Trypanosoma brucei parasites, respectively, the use of organometallic compounds may be a promising strategy. In this work, eight new heterobimetallic compounds are described including four 5-nitrofuryl containing thiosemicarbazones as bioactive ligands (HL1-HL4) and dppf = 1,1'-bis(diphenylphosphino) ferrocene as an organometallic co-ligand. Complexes of the formula [MII(L)(dppf)](PF6) with M = Pd or Pt were synthesized and fully characterized in the solid state and in solution, including the determination of the molecular structure of four of them by single crystal X-ray diffraction methods. Most compounds showed activity in the low micromolar or submicromolar range against both parasites, with the platinum compounds being more active than the palladium analogues. Activity was significantly increased by generation of the M-dppf compounds (3-24 fold increase with respect to free ligands HL for T. cruzi and up to 99 fold increase with respect to HL for T. brucei). The inclusion of the organometallic co-ligand also led to lower toxicity in mammalian cells and higher selectivity towards both parasites when compared to the free HL compounds. The complexes interact with DNA and affect the redox metabolism of the parasites. Furthermore, the most active and selective compound of the new series showed no in vivo toxicity in zebrafish embryos.

Platinum(II) metal complexes as potential anti-Trypanosoma cruzi agents.

In the search for new therapeutic tools against Chagas' disease (American Trypanosomiasis) two series of new platinum(II) complexes with bioactive 5-nitrofuryl containing thiosemicarbazones as ligands were synthesized, characterized and in vitro evaluated. Most of the complexes showed IC50 values in the muM range against two different strains of Trypanosoma cruzi, causative agent of the disease, being as active as the anti-trypanosomal drug Nifurtimox. In particular, the coordination of L3 (4-ethyl-1-(5-nitrofurfurylidene)thiosemicarbazide) to Pt(II) forming [Pt(L3)2] lead to almost a five-fold activity increase in respect to the free ligand. Trying to get an insight into the trypanocidal mechanism of action of these compounds, DNA and redox metabolism (intra-parasite free radical production) were evaluated as potential parasite targets. Results suggest that the complexes could inhibit parasite growth through a dual mechanism of action involving production of toxic free radicals by bioreduction and DNA interaction.

ESR, electrochemical and reactivity studies of antitrypanosomal palladium thiosemicarbazone complexes.

Cyclic voltammetry (CV) and electron spin resonance (ESR) techniques were used in the investigation of novel palladium complexes with bioactive thiosemicarbazones derived from 5-nitrofurane or 5-nitrofurylacroleine. Sixteen palladium complexes grouped in two series of the formula [PdCl(2)HL] or [PdL(2)] were studied. ESR spectra of the free radicals obtained by electrolytic reduction were characterized and analyzed. The ESR spectra showed two different hyperfine patterns. The stoichiometry of the complexes does not seem to affect significantly the hyperfine constants however we observed great differences between 5-nitrofurane and 5-nitrofurylacroleine derivatives. The scavenger properties of this family of compounds were lower than Trolox.

DNA conformational changes and cleavage by ruthenium(II) nitrofurylsemicarbazone complexes.

Metal complexes that establish interactions with DNA are being studied not only because of their potential use as therapeutic agents but also as tools for biochemistry and molecular biology. Searching for drugs with anti-trypanosome activity, we previously synthesized a series of ruthenium mixed ligand dimethyl sulfoxide complexes of the type [Ru(II)Cl(2)(DMSO)(2)L], where L is 5-nitrofurylsemicarbazone derivatives and DMSO is dimethyl sulfoxide. Though they present the ability to bind DNA, no activity against parasites in cell culture was observed. Considering their potential application as molecular tools we further analyzed the interactions with DNA through an electrophoretic approach. Non covalent withdrawal of superhelicity and a rapid nicking activity upon covalent interaction was observed. Inhibition of both effects was observed in the presence of distamycin suggesting the involvement of the DNA minor groove in the interaction with the nitrofurylsemicarbazone ruthenium complexes. In addition cleavage inhibition by dimethyl sulfoxide suggests an oxidative mechanism of action.

Vibrational spectra of palladium 5-nitrofuryl thiosemicarbazone complexes: experimental and theoretical study.

The vibrational spectroscopic behavior of a series of 16 palladium(II) complexes with 8 bioactive nitrofuran containing thiosemicarbazones as ligands has been studied in the solid state. The IR and Raman spectra of these complexes and the free nitrofuran thiosemicarbazone ligands were recorded and analyzed. Experimental spectra were satisfactorily described by density functional theory (DFT) calculations. The combination of experimental and theoretical methods allowed us to perform the characterization of the main vibrations that show the mode of coordination of the thiosemicarbazone moiety to palladium even though these vibration bands are located in spectral regions showing a complicated pattern due to the presence of vibrations of the nitrofuran moiety and combination modes involving furan vibrations. A characteristic vibrational spectroscopic pattern has been defined for Pd(II) 5-nitrofuryl thiosemicarbazone complexes. This systematic knowledge may be useful for the analysis of the spectroscopic behavior of other coordination compounds holding the 5-nitrofuran thiosemicarbazone moiety.