SERS as a tool for determination of structurally related compounds: The case of sulfanilamide class antibiotics.

Analysis of real objects based on surface-enhanced Raman spectroscopy (SERS) often utilizes new SERS substrates and/or complex analysis procedures, and they are optimized for only the determination of a single analyte. Moreover, analysis simplicity and selectivity are often sacrificed for maximum (sometimes unnecessary) sensitivity. Consequently, this trend limits the versatility of SERS analysis and complicates its practical implementation. Thus, we have developed a universal, but simple SERS assay suitable for the determination of structurally related antibiotics (five representatives of the sulfanilamide class) in complex objects (human urine and saliva). The assay involves only mixing of acidified analyzed solution with co-activating agent (polydiallyldimethylammonium chloride - PDDA) and SERS substrate (standard colloidal silver nanoparticles). Acidification promotes the generation of SERS spectra with maximum similarity and intensity, which is explained by the favorable enhancement of the protonated sulfanilamide moiety (a structurally similar part of the studied antibiotics) as a result of its strong electrostatic interaction with the SERS-active surface. Meanwhile, the addition of PDDA improves analysis selectivity by reducing background signal from body fluids, enabling to simplify sample pretreatment (dilution for urine; mucin removal and dilution for saliva). Therefore, the assay allows for rapid (≤10 min), precise, and accurate class-specific determination of sulfanilamides within concentration ranges suitable for non-invasive therapeutic drug monitoring in urine (40-600 µM) and saliva (10-30 µM). We also believe that thorough investigation of structurally related analytes and accompanying effects (e.g., high spectral similarity) is a promising direction to improve the understanding of SERS in general and expand its capabilities as an analytical tool.

A technique based on infrared spectroscopy for determining sulfanilamide levels sustainably: Progress and comparisons of greenness and whiteness using ComplexGAPI, AGREE, and RGB.

The study aimed to determine the potential of the infrared (IR) spectrophotometric technique for measuring the content of sulphanilamide with the sulfonamide group. The study aimed to obtain the IR spectra of sulfanilamide and use the -SO2 band at 1114.37 for the quantitative assay, determining its area under the curve (AUC). The study gives an alternative approach to existing analytical techniques that require vast amounts of organic solvents, which are costly and can be toxic, thus impacting the environment and increasing the analysis cost. The study evaluated the method's whiteness and greenness by utilizing the Complex green analytical procedure index, analytical GREEness calculator and Red Green Blue algorithm tool. The linierity was found to be 5 to 30 µg/ml. The present study has developed an infrared (IR) spectroscopic method that employs a straightforward sample preparation technique in methanol. The IR spectroscopic method's linearity range was determined to be 5-30 µg/ml. The p-value was 0.001 at 95 % confidence level assuring better recovery. This method is evaluated according to the Q2R1 ICH guideline. It is applicable to routine quality control analysis without pre-extraction using green IR spectroscopy. In conclusion, the study demonstrated that IR spectrophotometric techniques can quantify sulfanilamide while reducing the use of organic solvents, contributing to the green-and-white analytical chemistry approach. The developed methods are reliable, accurate, and cost-effective and have the potential to be implemented in routine analysis of sulfanilamide.

Selective Bacterial Growth Inactivation by pH-Sensitive Sulfanilamide Functionalized Carbon Dots.

Carbon dots (CDs) were synthesized hydrothermally by mixing citric acid (CA) and an antifolic agent, sulfanilamide (SNM), employed for pH sensing and bacterial growth inactivation. Sulfanilamide is a prodrug; aromatic hetero cyclization of the amine moiety along with other chemical modifications produces an active pharmacological compound (chloromycetin and miconazole), mostly administered for the treatment of various microbial infections. On the other hand, the efficacy of the sulfanilamide molecule as a drug for antimicrobial activity was very low. We anticipated that the binding of the sulfanilamide molecule on the carbon dot (CD) surface may form antibacterial CDs. Citric acid was hybridized with sulfanilamide during the hydrothermal preparation of the CDs. The molecular fragments of bioactivated sulfanilamide molecule play a crucial role in bacterial growth inactivation for Gram-positive and Gram-negative bacteria. The functional groups of citric acid and sulfanilamide were conserved during the CD formation, facilitating the zwitterionic behavior of CDs associated with its photophysical activity. At low concentrations of CDs, the antibacterial activity was apparent for Gram-positive bacteria only. This Gram-positive bacteria selectivity was also rationalized by zeta potential measurement.

Predicting sulfanilamide solubility in the binary mixtures using a reference solvent approach.

BACKGROUND: Solubility is a fundamental physicochemical property of active pharmaceutical ingredients. The optimization of a dissolution medium aims not only to increase solubility and other aspects are to be included such as environmental impact, toxicity degree, availability, and costs. Obtaining comprehensive solubility characteristics of chemical compounds is a non-trivial and demanding process. Therefore, support from theoretical approaches is of practical importance. OBJECTIVES: This study aims to examine the accuracy of the reference solubility approach in the case of sulfanilamide dissolution in a variety of binary solvents. This pharmaceutically active substance has been extensively studied, and a substantial amount of solubility data is available. Unfortunately, using this set of data directly for theoretical modeling is impeded by noticeable inconsistencies in the published solubility data. Hence, this aspect is addressed by data curation using theoretical and experimental confirmations. MATERIAL AND METHODS: In the experimental part of our study, the popular shake-flask method combined with ultraviolet (UV) spectrophotometric measurements was applied for solubility determination. The computational phase utilized the conductor-like screening model for real solvents (COSMO-RS) approach. RESULTS: The analysis of the results of solubility calculations for sulfonamide in binary solvents revealed abnormally high error values for acetone-ethyl acetate mixtures, which were further confirmed with experimental measurements. Additional confirmation was obtained by extending the solubility measurements to a series of homologous acetate esters. CONCLUSIONS: Our study addresses the crucial issue of coherence of solubility data used for many theoretical inquiries, including parameter fitting of semi-empirical models, in-depth thermodynamic interpretations and application of machine learning protocols. The effectiveness of the proposed methodology for dataset curation was demonstrated for sulfanilamide solubility in binary mixtures. This approach enabled not only the formulation of a consistent dataset of sulfanilamide solubility binary solvent mixtures, but also its implementation as a qualitative tool guiding rationale solvent selection for experimental solubility screening.

Sulfonamide drugs: Low-cost spectrofluorometric determination using a computer monitor calibrator for detection.

A possibility of the use of a common monitor calibrator as a portable and inexpensive tool for the fluorometric determination of sulfonamide drugs after their reaction with fluorescamine was examined. The luminescence measurements with a calibrator are based on irradiation of a test sample by the device lamp with a broadband spectrum in the visible and near UV regions and simultaneous registration of the secondary radiation by the device detector. Two types of cuvettes with black light absorbing sides eliminating the reflected self-radiation were tested. The commercially available Eppendorf-type black plastic microtubes ("LightSafe") were suggested as a good option for such measurements. It was shown that a monitor calibrator can be applied for optimization of the determination conditions. By the example of sulfanilamide and sulfamethazine, it was shown that the procedure should be carried out at pH 4-6 and fluorescamine concentration of 200 µmol L-1, and 40 min of the interaction. The limit of detection of sulfanilamide and sulfamethazine using a monitor calibrator is 0.9 µmol L-1 and 0.8 µmol L-1, respectively, which is comparable with their spectrophotometric determination.

Synthesis, Characterization, Anti-Glycation, and Anti-Oxidant Activities of Sulfanilamide Schiff Base Metal Chelates.

The current study reports synthesis, structure establishment, anti-glycation, and anti-oxidant activities of ligand 4-[(2-hydroxynaphthalene-1-ylmethylene)-amino]-benzenesulfonamide (L) and its coordination compounds with Mn(II), Co(II), Ni(II), Cu(II), and Zn(II) metal ions. The analytical techniques used (UV-Vis, FT-IR, CHN/S) confirmed the bidentate nature of the ligand, coordinating via O and N atoms in 2:1 ligand-to-metal ratio. The TG/DTA anylsis displayed that these compounds are thermally stable. Furthermore, the synthesized compounds were evaluated for their anti-glycation and antioxidant potential and showed significant activities with IC50 values range 184.11-386.34 µM and 37.05-126.27 µM, respectively. The Mn (IC50 = 184.11 ± 2.11 µM), Ni (IC50 = 211.26 ± 1.46 µM), Cu (IC50 = 254.56 ± 1.16 µM), and Zn (IC50 = 276.43 ± 2.14 µM) metal complexes exhibited substantial anti-glycation activity and comparatively better activity than the standard rutin (IC50 = 294.4 ± 1.50 µM), whereas Zn complex (IC50 = 37.05 ± 1.53 µM) also showed better DPPH radical scavenging activity than the standard tert-butyl-4-hydroxyanisole (IC50 = 44.7 ± 1.21 µM).

Design and synthesis of ciprofloxacin-sulfonamide hybrids to manipulate ciprofloxacin pharmacological qualities: Potency and side effects.

Fluoroquinolones are a class of antibacterial agents used clinically to treat a wide array of bacterial infections. Although being potent, susceptibility to CNS side effects limits their use. It was observed that improvements in absorption, activity and side effects were achieved via modifications at the N atom of the C7 of the side chain. To meet the increasing demand for development of new antibacterial agents, nineteen novel ciprofloxacin-sulfonamide hybrid molecules were designed, synthesized and characterized by IR, 1H NMR and 13C NMR as potential antibacterial agents with dual DNA gyrase/topoisomerase IV inhibitory activity. Most of the synthesized compounds showed significant antibacterial activity that was revealed by testing their inhibitory activity against DNA gyrase, DNA topoisomerase IV as well as their minimum inhibitory concentration against Staphylococcus aureus. Six ciprofloxacin-sulfonamide hybrids (3f, 5d, 7a, 7d, 7e and 9b) showed potent inhibitory activity against DNA topoisomerase IV, compared to ciprofloxacin (IC50: 0.55 µM), with IC50 range: 0.23-0.44 µM. DNA gyrase was also efficiently inhibited by five ciprofloxacin-sulfonamide hybrids (3f, 5d, 5e, 7a and 7d) with IC50 range: 0.43-1.1 µM (IC50 of ciprofloxacin: 0.83 µM). Compounds 3a and 3b showed a marked improvement in the antibacterial activity over ciprofloxacin against both Gram-positive and Gram-negative pathogens, namely, Staphylococcus aureus Newman and Escherichia coli ATCC8739, with MIC = 0.324 and 0.422 µM, respectively, that is 4.2-fold and 3.2-fold lower than ciprofloxacin (MIC = 1.359 µM) against the Gram-positive Staphylococcus aureus, and MIC = 0.025 and 0.013 µM, respectively, that is 10.2-fold and 19.6-fold lower than ciprofloxacin (MIC = 0.255 µM) against the Gram-negative Escherichia coli ATCC8739. Also, the most active compounds showed lower CNS and convulsive side effects compared to ciprofloxacin with a concomitant decrease in GABA expression.

Quantum chemical study the on interaction between sulfanilamide drug and MgO nanocluster.

The adsorption and interaction of sulfanilamide (SA) with a pristine magnesium oxide (MgO) nano-cage was scrutinized through density functional theory (DFT) calculations. All geometries were optimized at M06-2X/6-311G(d,p) level, and the single-point energy calculation was also carried out at the same level of theory. Also, natural bond orbital (NBO) analysis was carried out and the values related to Wiberg bond index (WBI), donor-acceptor interactions, and partial natural charges were inspected. The MgO nano-cage can adsorb SA more strongly with the adsorption energy (Eads) of - 41.74 kcal/mol, corresponding to the stable configurations. In addition, NBO analysis showed that the donor-acceptor interactions with SA and the MgO nano-cage are stronger. Based on our computations, the HOMO-LUMO gap of the MgO nano-cage changed to a great extent following the adsorption of the SA molecule, which corresponds to the most stable configuration that leads to improved electrical conductivity of the MgO nano-cage. The change in the gap determines the sensing mechanism, which is associated with the change in the electrical conductivity. To calculate the recovery time, transition-state theory (TST) was employed. Based on our calculation, Mg12O12-SA complex composites possess a short recovery time for the desorption of SA. The results show that the MgO nano-cage is an ideal candidate to be employed for developing SA sensors with high efficiency.

Molecular design and preparation of 2-aminothiazole sulfanilamide oximes as membrane active antibacterial agents for drug resistant Acinetobacter baumannii.

A series of 2-aminothiazole sulfanilamide oximes were developed as new membrane active antibacterial agents to conquer the microbial infection. Benzoyl derivative 10c was preponderant for the treatment of drug-resistant A. baumannii infection in contrast to norfloxacin and exerted excellent biocompatibility against mammalian cells including erythrocyte and LO2 cell line. Meanwhile, it had ability to eradicate established biofilm to alleviate the resistance burden. Mechanism investigation elucidated that compound 10c was able to disturb the membrane effectively and inhibit lactic dehydrogenase, which led to cytoplasmic content leakage. The cellular redox homeostasis was interfered via the production of reactive oxygen and nitrogen species (RONS), which further contributed to respiratory pathway inactivation and reduction of GSH activity. This work indicated that 2-aminothiazole sulfanilamide oximes could be a promising start for the exploitation of novel antibacterial agents against pathogens.

Synthesis, in vitro enzyme activity and molecular docking studies of new benzylamine-sulfonamide derivatives as selective MAO-B inhibitors.

Many studies have been conducted on the selective inhibition of human monoamine oxidase B (hMAO-B) enzyme using benzylamine-sulphonamide derivatives. Using various chemical modifications on BB-4h, which was reported previously by our team and showed a significant level of MAO-B inhibition, novel benzylamine-sulphonamide derivatives were designed, synthesised, and their MAO inhibition potentials were evaluated. Among the tested derivatives, compounds 4i and 4t achieved IC50 values of 0.041 ± 0.001 µM and 0.065 ± 0.002 µM, respectively. The mechanism of hMAO-B inhibition by compounds 4i and 4t was studied using Lineweaver-Burk plot. The nature of inhibition was also determined to be non-competitive. Cytotoxicity tests were conducted and compounds 4i and 4t were found to be non-toxic. Molecular docking studies were also carried out for compound 4i, which was found as the most potent agent, within hMAO-B catalytic site.

Synthesis and biological evaluation of Val-Val dipeptide-sulfonamide conjugates.

Novel Val-Val dipeptide-benzenesulfonamide conjugates were reported in this study. These were achieved by a condensation reaction of p-substituted benzenesulfonamoyl alkanamides with 2-amino-4-methyl-N-substituted phenyl butanamide using classical peptide-coupling reagents. The compounds were characterized using Fourier transform infrared, 1 H-nuclear magnetic resonance (NMR), 13 C-NMR, and electrospray ionization-high-resolution mass spectrometry spectroscopic techniques. As predicted from in silico studies, the Val-Val dipeptide-benzenesulfonamide conjugates exhibited antimalarial and antioxidant properties that were analogous to the standard drug. The synthesized compounds were evaluated for in vivo antimalarial activity against Plasmodium berghei. The hematological analysis was also conducted on the synthesized compounds. At 50 mg/kg body weight, compounds 8a, 8d, and 8g-i inhibited the multiplication of the parasite by 48-54% on Day 7 of posttreatment exposure, compared with the 67% reduction with artemisinin. All the synthesized dipeptides had a good antioxidant property, but it was less when compared with vitamin C. The dipeptides reported herein showed the ability to reduce oxidative stress arising from the malaria parasite.

Biological properties of sulfanilamide-loaded alginate hydrogel fibers based on ionic and chemical crosslinking for wound dressings.

In this work, alginate hydrogel fibers loading sulfanilamide were proposed using a combination of Ca2+ ions and glutaraldehyde crosslinking to develop an efficient wound dressing. The structure, mechanical properties, absorbency, in vitro drug release and cytotoxicity of the proposed alginate hydrogel fibers were investigated systematically. The results indicated that crosslinking with glutaraldehyde can efficiently enhance the mechanical properties of the alginate hydrogel fibers, and reduce their swelling degree which is beneficial for hydrogel fibers to obtain adjustable fluid adsorption capacity, sustained drug release feature over hydrogel fibers crosslinked only by Ca2+ ions. Antibacterial activity assay demonstrated the bactericidal ability of the alginate hydrogel fibers towards S. aureus and E. coli with the highest antibacterial rate of 99.9%. Furthermore, a preliminary trial of papermaking process for producing alginate hydrogel mats showed the workability and the applicability of the mechanically tough hydrogel fibers. Cytotoxicity assay indicated the enhancement of cell adhesion and proliferation, revealing the non-cytotoxicity and biocompatibility of the alginate hydrogel mats. Based on the excellent mechanical strength, adjustable fluid adsorption capacity, sustained drug release, and biocompatibility, the bi-crosslinked alginate hydrogel fibers had a promising application as ideal wound dressings in clinic.

Substituted sulfonamide bioisosteres of 8-hydroxyquinoline as zinc-dependent antibacterial compounds.

A series of substituted sulfonamide bioisosteres of 8-hydroxyquinoline were evaluated for their antibacterial activity against the common mastitis causative pathogens Streptococcus uberis, Staphylococcus aureus and Escherichia coli, both in the presence and absence of supplementary zinc. Compounds 9a-e, 10a-c, 11a-e, 12 and 13 were demonstrated to have MICs of 0.0625 µg/mL against S. uberis in the presence of 50 µM ZnSO4. Against S. aureus compounds 9g (MIC 4 µg/mL) and 11d (MIC 8 µg/mL) showed the greatest activity, whereas all compounds were found to be inactive against E. coli (MIC > 256 µg/mL); again in the presence of 50 µM ZnSO4. All compounds were demonstrated to be significantly less active in the absence of supplementary zinc. Compound 9g was subsequently confirmed to be bactericidal, with an MBC (≥3log10 cfu/mL reduction) of 0.125 µg/mL against S. uberis in the presence of 50 µM ZnSO4. To validate the sanitising activity of compound 9g in the presence of supplementary zinc, a quantitative suspension disinfection (sanitizer) test was performed. In this preliminary test, sanitizing activity (>5log10 reduction of CFU/mL in 5 min) was observed against S. uberis for compound 9g at concentrations as low as 1 mg/mL, validating the potential of this compound to function as a topical sanitizer against the major environmental mastitis-causing microorganism S. uberis.

Sulfonamide Inhibition Studies of the ß-Class Carbonic Anhydrase CAS3 from the Filamentous Ascomycete Sordaria macrospora.

A new ß-class carbonic anhydrase was cloned and purified from the filamentous ascomycete Sordaria macrospora, CAS3. This enzyme has a higher catalytic activity compared to the other two such enzymes from this fungus, CAS1 and CAS2, which were reported earlier, with the following kinetic parameters: kcat of (7.9 ± 0.2) × 105 s-1, and kcat/Km of (9.5 ± 0.12) × 107 M-1∙s-1. An inhibition study with a panel of sulfonamides and one sulfamate was also performed. The most effective CAS3 inhibitors were benzolamide, brinzolamide, dichlorophnamide, methazolamide, acetazolamide, ethoxzolamide, sulfanilamide, methanilamide, and benzene-1,3-disulfonamide, with KIs in the range of 54-95 nM. CAS3 generally shows a higher affinity for this class of inhibitors compared to CAS1 and CAS2. As S. macrospora is a model organism for the study of fruiting body development in fungi, these data may be useful for developing antifungal compounds based on CA inhibition.

Design and biological evaluation of a novel type of potential multi-targeting antimicrobial sulfanilamide hybrids in combination of pyrimidine and azoles.

This work explored a novel type of potential multi-targeting antimicrobial three-component sulfanilamide hybrids in combination of pyrimidine and azoles. The hybridized target molecules were characterized by 1H NMR, 13C NMR and HRMS spectra. Some of the developed target compounds exerted promising antimicrobial activity in comparison with the reference drugs norfloxacin and fluconazole. Noticeably, sulfanilamide hybrid 5c with pyrimidine and indole could effectively inhibit the growth of E. faecalis with MIC value of 1 µg/mL. The active molecule 5c showed low cell toxicity and did not obviously trigger the development of resistance towards the tested bacteria strains. Mechanism exploration indicated that compound 5c could not only exert efficient membrane permeability, but also intercalate into DNA of resistant E. faecalis to form 5c-DNA supramolecular complex, which might be responsible for its antimicrobial action. The further investigation showed that this molecule could be effectively transported by human serum albumins through hydrogen bonds and van der Waals force.

N-doped Cu-MOFs for efficient electrochemical determination of dopamine and sulfanilamide.

Fast and efficient tracking of micropollutants in aquatic environment by developing novel electrode materials is of great significance. Herein, a polyvinylpyrrolidone (PVP) assisted strategy is applied for synthesis of nitrogen doped Cu MOFs (N-Cu-MOF) for micropollutants electrochemical detection. The designed N-Cu-MOFs possess uniform octahedral shape with large surface area (1184 m2 g-1) and an average size of roughly 450 nm, exhibiting the excellent electroanalytical capability for the detection of multipollutants. In the case of dopamine (DA) and sulfonamides (SA) as typical microcontaminants, the designed N-Cu-MOFs exhibited wide linear ranges of 0.50 nM-1.78 mM and low detection limit (LOD, 0.15 nM, S/N = 3) for the determination of DA, as well as a linear range of 0.01-58.3 µM and LOD (0.003 µM, S/N = 3) for monitoring SA. The improved performance is attributed to the heteroatom introduction and good dispersion stability of N-Cu-MOF with PVP-decorated. The good electroanalytical ability of N-Cu-MOF for detection of DA and SA can provide a guide to efficient and rapid monitor other micropollutants and construct novel electrochemical sensors.

Synthesis of long-tail nonionic surfactants and their investigation for vesicle formation, drug entrapment, and biocompatibility.

Nonionic surfactants have an extraordinary fascination for the researchers in the field of drug delivery for enhancing drug bioavailability and therapeutic efficacy. Here, we are reporting the synthesis, characterization, drug entrapment efficiency (EE), critical micellar concentration, and biocompatibility evaluation of sulphanilamide based new nonionic surfactants. The surfactants were synthesized in single step reactions and characterized through 1H NMR, FT-IR, and mass spectrometric analysis. The surfactants abilities for niosomal vesicles formation were investigated utilizing Ciprofloxacin as a model drug. The drug loaded niosomal suspension of the synthesized surfactants was screened for shape; size, polydispersity index, and drug EE utilizing AFM, Zetasizer, and UV, respectively. The compatibility of the drug in drug loaded vesicles with excipients was assessed utilizing FT-IR spectroscopy. The biocompatibility of the synthesized surfactants was assessed through blood haemolysis and cell cytotoxicity assays. Results of this study showed that the synthesized surfactants were quite haemocompatible and nontoxic in nature and were able to form spherical vesicles. The size and drug EE of the vesicles were dependant on the length of surfactant aliphatic chain. Surfactant with long aliphatic chain was more efficient in entrapping the drug and could be used as a potential vesicular drug delivery vehicle for improving the lipophilic drug's bioavailability.

Development and Validation of the Simple and Sensitive Spectrophotometric Method of Amoxicillin Determination in Tablets using Sulphanilamides.

A rapid, simple and sensitive spectrophotometric method for the determination of amoxicillin (AM) is described. The method is based on the previous sulphanilamide (SA) and sulphathiazole (STZ) diazotization in the medium of 0.6-0.7 M hydrochloric acid and their subsequent interaction with amoxicillin at pH = 10.5 with formation of yellow-colored azo compouds. Effective molar absorptivities at the absorbance maxima at 445 nm (SA) and 448 nm (STZ) for azo compounds were (1.74 ± 0,06)∆104 L×mol-1×cm-1 and (1.97 ± 0,05)∆104 L×mol-1×cm-1, respectively. Stoichiometric ratios of the components of azo compounds were determined using continuous variations method. Based on the optimum reaction conditions, new methods were developed. These methods allow to determine the amoxicillin in concentration range 1.3-32.9 mg×mL-1 with sulphanilamide and 0.7-27.4 mg×mL-1 with sulphathiazole. The methods were successfully validated for amoxicillin determination in tablets "Amoxil".

Voltammetric Determination of Binding Constant and Stoichiometry of Albumin (Human, Bovine, Ovine)-Drug Complexes.

The parameters characterizing the formation of complexes with albumin (in particular, human serum albumin (HSA)) are fundamental for the characterization of a drug for commercialization purposes and for the determination of common pharmacokinetic parameters. Electrochemical methods appear particularly attractive for the determination of the complexation constant, complex stoichiometry, and percentage of free/bound drug, due to the ease of operation and the wide availability. In this article, we propose an electrochemical method based on differential pulse voltammetry for the determination of albumin-drug interaction parameters, including the replacement of the drug-albumin adduct by a competitive compound, sulfanilamide. The formation of either single or multiple complexes between the considered drug and albumin has been considered. Typically, the method operates with a glassy carbon electrode in NaCl 0.9% as the supporting electrolyte.

A CuAAC Click Approach for the Introduction of Bidentate Metal Complexes to a Sulfanilamide-Derived Antibiotic Fragment.

A simple "click-chemistry" approach was employed in order to functionalize the known antibiotic fragment sulfanilamide with a bidentate pyridyl-triazole pocket, which allowed for the synthesis of ruthenium(II) and rhenium(I) carbonyl chloride complexes. Six new complexes were prepared and comprehensively characterized, including five single crystal X-ray structures, photophysical characterization, and testing for antimicrobial activity. Interestingly, functionalization of the pyridine ring with an ortho-hydroxymethyl group resulted in a greater than 100-fold increase in the rate of ligand release in a dimethylsulfoxide solution. Subsequent studies indicated this process could be further accelerated by irradiation with 265 nm light. Structural characterization of four of the complexes indicates that this is the result of a lengthening and weakening of the Re-NPyridine bond (average (Ltri) = 2.19 Å vs LtriOH = 2.25 Å) due to the steric influence of the hydroxymethyl group. The organometallic rhenium(I) pyridyl-triazole functionality maintains its characteristic fluorescent properties despite the presence of the sulfonamide moiety. Two of the compounds showed modest antimicrobial activity against methicillin-resistant Staphylococcus aureus, whereas the structurally similar sulfamethoxazole alone showed no activity under the same conditions.