Sulfonamide Molecule Research Articles

Ceria-Catalyzed Hydrolytic Cleavage of Sulfonamides.

Nanoceria is a promising nanomaterial for the catalytic hydrolysis of a wide variety of substances. In this study, it was experimentally demonstrated for the first time that CeO2 nanostructures show extraordinary reactivity toward sulfonamide drugs (sulfadimethoxine, sulfamerazine, and sulfapyridine) in aqueous solution without any illumination, activation, or pH adjustment. Hydrolytic cleavage of various bonds, including S-N, C-N, and C-S, was proposed as the main reaction mechanism and was indicated by the formation of various reaction products, namely, sulfanilic acid, sulfanilamide, and aniline, which were identified by HPLC-DAD, LC-MS/MS, and NMR spectroscopy. The kinetics and efficiency of the ceria-catalyzed hydrolytic cleavage were dependent on the structure of the sulfonamide molecule and physicochemical properties of Nanoceria prepared by three different precipitation methods. However, in general, all three ceria samples were able to cleave SA drugs tested, proving the robust and unique surface reactivity toward these compounds inherent to cerium dioxide. The demonstrated reactivity of CeO2 to molecules containing sulfonamide or even sulfonyl (and similar) functional groups may be significant for both heterogeneous catalysis and environmentally important degradation reactions.

The effects of UiO-66 ultrafine particles on the rapid detection of sulfonamides in milk: Adsorption performance and mechanism.

Nanoscale MOFs particles possess both excellent adsorption and dispersion properties. In this study, ultrafine particles UiO-66 (UP/UiO-66) with a particle size below 50nm were synthesised by a template-controlled method. UP/UiO-66 was able to achieve a maximum adsorption capacity of 139.64mg/g for 5 methoxylated sulfonamides. Adsorption studies showed that UP/UiO-66 adsorption of sulfonamides can be classified as a pseudo-secondary kinetic adsorption model for single molecular layer adsorption. ELISA (validated by Raman and molecular docking) showed that the sulfonamide molecule was still immunoreactive with antibodies after adsorption by UP/UiO-66. In 15min, UP/UiO-66 could be used directly in the ELISA test for sulfonamides in milk without elution and separation. The LOQ (IC20) of UP/UiO-66-ELISA for sulfonamides in milk was 0.21-2.05ng/mL. The ultrafine particle strategy of UiO-66 is expected to be applied to other MOFs and used as a general pretreatment material for residue monitoring in complex matrices.

Adsorption characteristics of sulfonamide antibiotic molecules on carbon nanotube and the effects of environment

In this paper, the adsorption characteristics of five sulfonamide antibiotic molecules on carbon nanotubes were investigated using density functional theory (DFT) calculations. The adsorption configurations of different adsorption sites were optimized, and the most stable adsorption configuration of each sulfonamide molecule was determined by adsorption energy comparison, and the relative adsorption stability of five sulfonamide molecules on carbon nanotubes was determined by comparing their adsorption energies, i.e., sulfamethazine > sulfadiazine > sulfamerazine > sulfamethoxazole > sulfanilamide. The electron densities of the adsorption configurations were then calculated to confirm that the adsorption of five sulfonamide drug molecules on carbon nanotubes should be physical adsorption. Moreover, the adsorption energy of five sulfonamide molecules on carbon nanotubes in the aqueous environment was larger than that in the vacuum even though the adsorption process remain to be physical adsorption. The adsorption characteristics of the five sulfonamide molecules in various acid-base environments were finally investigated. In contrast, the adsorption energies of the five drug molecules in acid-base environments were significantly reduced, indicating that carbon nanotubes may need to have a suitable pH range to achieve the optimal adsorption effect when they are used for the treatment of sulfonamide antibiotics. In this paper, we use density functional theory (DFT) with PBE functional to study the adsorption properties of five sulfonamides on carbon nanotubes. The structural optimization and the calculation of electronic structural properties are carried out by CP2K package (version 7.1), adopting the DZVP-MOLOPT-SR-GTH basis set and Goedeck-Teter-Hutter (GTH) pseudo potential. Grimme's D3 correction is used to during all the calculations to correctly capture the influence of the van der Waals interactions.

Computational Investigation on Structural and Reactive Sites (HOMO-LUMO, MEP, NBO, NPA, ELF, LOL, RDG) Identification, Pharmacokinetic (ADME) Properties and Molecular Docking Investigation of (E)-4-((4-chlorobenzylidene) amino) Benzene Sulfonamide Compound

(E)-4-((4-chlorobenzylidene) amino) benzene sulfonamide molecule has been optimized and characterized by DFT/B3LYP/6-311++G(d,p) quantum computational method. Mulliken and Fukui function analysis have been done to know the chemical reactivity of the compound. MEP for electrophilic, nucleophilic attack and FMO for electronic transitions have been explained. (ADME) Adsorption Spreading Metabolism and excretion, molecular physicochemical mechanism, inter and intramolecular hydrogen bonding, hyperconjugation, NLO have also been studied. ELF and LOL have been visualized using multiwfn to study about the electronic environment of the molecule. Molecular docking and drug likeness have been performed to know the biological activity of the compound.

B36 bowl-like structure as nanocarrier for sulfonamides: a theoretical study

Density functional theory method used to investigate the interaction of the simplest sulfonamide with the B36 nanocluster. The obtained results indicate that although sulfonamide weakly interacts with convex and concave sides of the nanocluster, the B atom at the edge of B36 nanocluster is favorable position for adsorbing. The interactions have been also studied in terms of natural bond order charges analysis. The electronic properties of the nanocluster are significantly altered once the sulfonamide molecule is adsorbed. Thus, the energy gap between HOMO and LUMO orbitals is reduced which could be applied as a chemical signal. Moreover, the relative high dipole moments obtained for B36/sulfonamide configurations suggest that these structures could be solubilized or dispersed in polar mediums like water. According to the results obtained, the B36 nanostructure could be a potential carrier for delivering sulfonamides in nanomedicine applications.

A density functional theory outlook on the possible sensing ability of boron nitride nanotubes and their Al- and Si-doped derivatives for sulfonamide drugs

ABSTRACTIn this study, the adsorption behavior of boron nitride nanotubes (BNNTs) and their Al- and Si-doped BNNTs toward sulfonamide (SA) drugs is explored using density functional theory (DFT) calculations. Total energies, geometry optimizations, frontier molecular orbital (FMO) and density of state (DOS) analyses were obtained using M06-2X level of theory and the 6-311G(d) basis sets. In the most stable conformation, adsorption energies of the sulfonamide molecule over pristine BNNTs, Al-BNNTs, Si-BNNTs are 25.9, 59.7 and 51.7 kcal/mol, respectively. The HOMO–LUMO gap, Eg, which corresponds to sensing ability, is the most for pristine BNNTs toward SA indicating that BNNTs can be a promising candidate for sensing SA. On the other hand, Al-BNNTs and Si-BNNTs cannot used for sensing SA.

Crystal Engineering for Intramolecular π–π Stacking: Effect of Sequential Substitution of F on Molecular Geometry in Conformationally Flexible Sulfonamides

A small library of ten sulfonamide derivatives comprising two aromatic rings was synthesized to investigate the effect of chronological positioning of the F-atom on the intramolecular π-stacking assembly. The sequential positioning of F-atoms was carried out on one of the aromatic rings that is linked to the sulfonamide moiety directly while the other aromatic ring (phenyl or pyridine) is linked by an ethyl spacer with the sulfonamide moiety. The ethyl spacer is provided to achieve the required flexibility so that both aromatic rings can bend to acquire syn conformation facilitated π-stacking between electron-deficient and electron-rich aromatic rings. The idea was to study the interplay between hydrogen bonding and π-stacking synthons in the conformationally flexible sulfonamide derivatives. The solid-state conformation of all the derivatives was investigated using the single-crystal X-ray diffraction technique. Crystal structure analysis revealed that the syn conformation was achieved only in trifluoro and pentafluoro sulfonamide derivatives with benzene substitution while in all other derivatives the molecules take either midway or anti conformations. None of the sulfonamide molecules with a pyridine moiety showed syn conformation. It could be because of the involvement of the pyridine N-atom in the hydrogen bonding dimeric synthon. The molecular conformation study in solution state using 2D NOESY and HOESY NMR experiments also substantiated syn conformation in a pentafluoro sulfonamide molecule with benzene substitution. The conformational analysis carried out employing density functional theory (DFT) calculations confirmed higher stability for the syn conformation over midway and anti orientations.

Synthesis, characterization and computational study of the newly synthetized sulfonamide molecule

A new compound N-(2,5-dimethyl-4-nitrophenyl)-4-methylbenzenesulfonamide (NDMPMBS) has been derived from 2,5-dimethyl-4-nitroaniline and 4-methylbenzene-1-sulfonyl chloride. Structure was characterized by SCXRD studies and spectroscopic tools. Compound crystallized in the monoclinic crystal system with P21/c space group a = 10.0549, b = 18.967, c = 8.3087, β = 103.18 and Z = 4. Type and nature of intermolecular interaction in crystal state investigated by 3D-Hirshfeld surface and 2D-finger print plots revealed that title compound stabilized by several interactions. The structural and electronic properties of title compound have been calculated at DFT/B3LYP/6-311G++(d,p) level of theory. Computationally obtained spectral data was compared with experimental results, showing excellent mutual agreement. Assignment of each vibrational wave number was done on the basis of potential energy distribution (PED). Investigation of local reactivity descriptors encompassed visualization of molecular electrostatic potential (MEP) and average local ionization energy (ALIE) surfaces, visualization of Fukui functions, natural bond order (NBO) analysis, bond dissociation energies for hydrogen abstraction (H-BDE) and radial distribution functions (RDF) after molecular dynamics (MD) simulations. MD simulations were also used in order to investigate interaction of NDMPMBS molecule with 1WKR and 3ETT proteins protein.

Molecular dynamics-assisted pharmacophore modeling of caspase-3-isatin sulfonamide complex: Recognizing essential intermolecular contacts and features of sulfonamide inhibitor class for caspase-3 binding

The identification of isatin sulfonamide as a potent small molecule inhibitor of caspase-3 had fuelled the synthesis and characterization of the numerous sulfonamide class of inhibitors to optimize for potency. Recent works that relied on the ligand-based approaches have successfully shown the regions of optimizations for sulfonamide scaffold. We present here molecular dynamics-based pharmacophore modeling of caspase-3-isatin sulfonamide crystal structure, to elucidate the essential non-covalent contacts and its associated pharmacophore features necessary to ensure caspase-3 optimal binding. We performed 20ns long dynamics of this crystal structure to extract global conformation states and converted into structure-based pharmacophore hypotheses which were rigorously validated using an exclusive focussed library of experimental actives and inactives of sulfonamide class by Receiver Operating Characteristic (ROC) statistic. Eighteen structure-based pharmacophore hypotheses with better sensitivity and specificity measures (>0.6) were chosen which collectively showed the role of pocket residues viz. Cys163 (S1 sub-site; required for covalent and H bonding with Michael acceptor of inhibitors), His121 (S1; π stack with bicyclic isatin moiety), Gly122 (S1; H bond with carbonyl oxygen) and Tyr204 (S2; π stack with phenyl group of the isatin sulfonamide molecule) as stringent binding entities for enabling caspase-3 optimal binding. The introduction of spatial pharmacophore site points obtained from dynamics-based pharmacophore models in a virtual screening strategy will be helpful to screen and optimize molecules belonging to sulfonamide class of caspase-3 inhibitors.

N-(6-Methylpyridin-2-yl)mesitylenesulfonamide and acetic acid--a salt, a cocrystal or both?

In the solid obtained from N-(6-methylpyridin-2-yl)mesitylenesulfonamide and acetic acid, the constituents interact via two N-H···O hydrogen bonds. The H atom situated in one of these short contacts is disordered over two positions: one of these positions is formally associated with an adduct of the neutral sulfonamide molecule and the neutral acetic acid molecule, and corresponds to a cocrystal, while the alternative site is associated with salt formation between a protonated sulfonamide molecule and deprotonated acetic acid molecule. Site-occupancy refinements and electron densities from difference Fourier maps suggest a trend with temperature, albeit of limited significance; the cocrystal is more relevant at 100 K, whereas the intensity data collected at room temperature match the description as cocrystal and salt equally well.

4-Amino-N-(4,6-dimethylpyrimidin-2-yl)benzenesulfonamide–1,4-diazabicyclo[2.2.2]octane (2/1)

The asymmetric unit of the title co-crystal, C12H14N4O2S·0.5C6H12N2, comprises the sulfonamide mol­ecule and half a mol­ecule of 1,4-di­aza­bicyclo­[2.2.2]octane (DABCO), the latter being disposed about a crystallographic twofold rotation axis. In the sulfonamide mol­ecule, the aromatic rings are almost perpendicular to one another [dihedral angle = 75.01 (8)°]. In the crystal, mol­ecules are connected into a three-mol­ecule aggregate via amide–DABCO N—H⋯N hydrogen bonds, and these are connected into a three-dimensional architecture via amino–DABCO N—H⋯O and amino-pyrimidine N—H⋯N hydrogen bonds.

N-(1-Allyl-1H-indazol-5-yl)-4-methoxybenzenesulfonamide hemihydrate

In the title compound, C17H17N3O3 .0.5H2O, the indazole system makes a dihedral angle of 46.19 (8)° with the plane through the benzene ring and is nearly perpendicular to the allyl group, as indicated by the dihedral angle of 81.2 (3)°. In the crystal, the water mol­ecule, disordered over two sites related by an inversion center, forms O—H⋯N bridges between indazole N atoms of two sulfonamide mol­ecules. It is also connected via N—H⋯O inter­action to the third sulfonamide mol­ecule; however, due to the water mol­ecule disorder, only every second mol­ecule of sulfonamide participates in this inter­action. This missing inter­action results in a slight disorder of the sulfonamide S,O and N atoms which are split over two sites with half occupancy. With the help of C–H⋯O hydrogen bonds, the mol­ecules are further connected into a three-dimensional network.

Solid-State Form Screen of Cardiosulfa and Its Analogues

Cardiosulfa is a biologically active sulfonamide molecule that was recently shown to induce abnormal heart development in zebrafish embryos through activation of the aryl hydrocarbon receptor (AhR). The present report is a systematic study of solid-state forms of cardiosulfa and its biologically active analogues that belong to the N-(9-ethyl-9H-carbazol-3-yl)benzene sulfonamide skeleton. Cardiosulfa (molecule 1; R(1) = NO2, R(2) = H, R(3) = CF3), molecule 2 (H, H, CF3), molecule 3 (CF3, H, H), molecule 4 (NO2, H, H), molecule 5 (H, CF3, H), and molecule 6 (H, H, H) were synthesized and subjected to a polymorph search and solid-state form characterization by X-ray diffraction, differential scanning calorimetry (DSC), variable-temperature powder X-ray diffraction (VT-PXRD), FTIR, and solid-state (ss) NMR spectroscopy. Molecule 1 was obtained in a single-crystalline modification that is sustained by N-H⋅⋅⋅π and C-H⋅⋅⋅O interactions but devoid of strong intermolecular N-H⋅⋅⋅O hydrogen bonds. Molecule 2 displayed a N-H⋅⋅⋅O catemer C(4) chain in form I, whereas a second polymorph was characterized by PXRD. The dimorphs of molecule 3 contain N-H⋅⋅⋅π and C-H⋅⋅⋅O interactions but no N-H⋅⋅⋅O bonds. Molecule 4 is trimorphic with N-H⋅⋅⋅O catemer in form I, and N-H⋅⋅⋅π and C-H⋅⋅⋅O interactions in form II, and a third polymorph was characterized by PXRD. Both polymorphs of molecule 5 contain the N-H⋅⋅⋅O catemer C(4) chain, whereas the sulfonamide N-H⋅⋅⋅O dimer synthon R2(2)(8) was observed in polymorphs of 6. Differences in the strong and weak hydrogen-bond motifs were correlated with the substituent groups, and the solubility and dissolution rates were correlated with the conformation in the crystal structure of 1-6. Higher solubility compounds, such as 2 (10.5 mg mL(-1)) and 5 (4.4 mg mL(-1)), adopt a twisted confirmation, whereas less-soluble 1 (0.9 mg mL(-1)) is nearly planar. This study provides practical guides for functional-group modification of drug lead compounds for solubility optimization.

Photocatalytic Degradation of Sulfonamides over the Short Multi-Walled Carbon Nanotube-TiO<sub>2</sub> Hybrid

The short multi-walled carbon nanotube-TiO2 (SMWNT-TiO2) hybrid was synthesized via direct growth of TiO2 nanoparticles on the surface of the functionalized SMWNTs by the hydrothermal treatment and utilized as the photocatalyst in the sulfonamides degradation under UV light irradiation. The photodegradation efficiency of sulfonamides was examined by HPLC technique, which demonstrates that sulfonamides can be readily degraded under UV light irradiation. However, the four sulfonamides have different degradation rates, which is in the order of sulfadimidine > sulfanilamide > sulfamethoxazole > sulfathiazole. These experimental results can be attributed to the point charge of the atoms in the sulfonamide molecule and its adsorption on the surface of the SMWNT-TiO2 hybrid.

(E)-4-Amino-N-(1,2-dihydropyridin-2-ylidene)benzenesulfonamide nitromethane monosolvate

In the title solvate, C11H11N3O2S·CH3NO2, the dihedral angle between the benzene ring and the N-containing ring is 85.94 (11)°, and an approximate V shape arises for the sulfonamide mol­ecule. In the crystal, N—H⋯O and N—H⋯N hydrogen bonds and weak C—H⋯O inter­actions link the sulfonamide mol­ecules into a three-dimensional network. The nitro­methane solvent mol­ecules are located in the inter­stitial sites in the sulfonamide network.

Two Novel Potential Anticonvulsant Salts of 5-Amino-2-Sulfonamide-1,3,4-Thiadiazole

Two crystal structures of sulfonamide salts were studied by X-Ray diffraction. The compound C2H5N4O2S2 +·H2O·Cl− (I), (Hats·H2O·Cl, Hats = protonated 5-amino-2-sulfonamide-1,3,4-thiadiazole) crystallizes in orthorhombic space group, P212121, with unit cell parameters a = 10.047(4), b = 5.186(2), c = 16.766(6) A and the compound C2H5N4O2S2 +·CH3O3S− (II), crystallizes in monoclinic space group, Cc, with unit cell parameters a = 5.378(3), b = 19.707(6), c = 10.014(5) A, beta = 99.97(1)°. The molecules in compound I are arranged in a helix of alternating water and Hats molecules. Helixes are interconnected by hydrogen bonds provided by Cl− ions and one ring with a graph set R 6 4 (12) is determined. The crystal structure of compound II presents mesylate and Hats molecules bonded by two hydrogen bond determining a ring with a graph set R 2 2 (8). Two substituted sulfonamide salts were obtained, the hydrochloride is monohydrate and develops a helix arrangement of alternating water/sulfonamide molecules, meanwhile the mesylate is bonded to sulfonamide molecule determining a ring, with a graph set R 2 2 (8).

The anilinium chloride adduct of 4-bromo-N-phenylbenzenesulfonamide

The title compound anilinium chloride-4-bromo-N-phenyl-benzenesulfonamide (1/1), C 6 H B N + ·Cl - ·C 12 H 10 BrNO 2 S, displays a hydrogen-bonded ladder motif with four independent N-H···-Cl bonds in which both the NH group of the sulfonamide molecule and the NH 3 group of the anilinium ion [N···Cl = 3.135 (3)-3.196 (2) A and N-H···Cl = 151-167] are involved. This hydrogen-bonded chain contains two independent R 2 4 (8) rings and each chloride ion acts as an acceptor of four hydrogen bonds.

Generation of group-specific antibodies against sulfonamides.

To develop a sulfonamide-specific ELISA, different attempts were made to obtain monoclonal antibodies specific for the common structure of sulfonamides. In a first approach, sulfanilamide was linked to albumins using glutaraldehyde or a succinimide ester as cross-linker. A weak immune response or none at all was induced after immunization of mice with those conjugates. High antibody titers were obtained with conjugates where sulfanilamide was linked to albumins or casein (azocasein) with a diazotation reaction. However, the antibodies were only highly specific for the bound sulfanilamide molecule. In a second approach, sulfonamide-protein conjugates were used in which the sulfonamide molecule is linked at its side chain, leaving the common structure of sulfonamides unchanged. Three sulfonamide derivatives (S, TS, and PS, previously described in the literature) containing a carboxyl group in their side chain were linked to proteins using a carbodiimide mediated reaction. Immunization with the S-conjugates led to high antibody titers, but the antibodies were only highly specific for the bound S-molecule. Group-specific antibodies were obtained after immunization with the PS- and TS-conjugates. It was described that immunization with PS-conjugates lead to the recognition of other sulfonamides (sulfamethazine, -merazine, -diazine, and -dimethoxine) that are not well recognized by antibodies induced after immunization with TS-conjugates. Therefore, we tried to guide the immune response in the direction of recognition of the common structure of sulfonamides by immunizing the animals alternately with PS- and TS-conjugates. The polyclonal antibodies of the mice indeed had a broader specificity, but the specificity of the monoclonals obtained after fusion experiments was not influenced. Immunization with TS-conjugates seemed sufficient to obtain sulfonamide-specific monoclonal antibodies. With the best monoclonal (mAb 3B5B10E3) two competitive inhibition (ci) ELISA's were developed: one coated with antigen and the other coated with the monoclonal antibody. Sulfadiazine, -dimethoxine, -thiazole, -pyridine, and -methoxazole were detected in both ELISA's at their MRL-value (100 ppb) in buffer solution. Sulfadiazine, sulfathiazole, and sulfamethoxazole could even be detected at 10 ppb.

Cobinding of bilirubin and sulfonamide and of two bilirubin molecules to human serum albumin: A site model

Differential light absorption spectra of the bilirubin-albumin 1:1 complex, obtained on addition of 20 different sulfonamides, differ with respect to shape and amplitude. This finding seems to indicate that the sulfonamide molecule is bound in direct touch with the bilirubin. The light absorption spectrum of bilirubin-albumin 1:1 undergoes changes on cobinding of a fatty acid anion, laurate, and on variation of pH, previously explained by a change of dihedral angle between the two chromophores of the bilirubin molecule. In bilirubin-albumin 2:1, binding of laurate and variation of pH cause little change of the spectrum. This is best explained by binding of the two bilirubin molecules in close proximity, preventing conformational changes in the complex. From measurements of fluorescence of the lone tryptophan group in albumin and quenching on binding of bilirubin, we calculated the distance of 22 Å from tryptophan to the first bound bilirubin molecule, and of 18 Å to the second. Mutual quenching of the bilirubin fluorescence from two bound bilirubin molecules seemed to indicate that the two are bound closely together. A model of bilirubin-albumin with a binding site capable of accommodating one bilirubin and one sulfonamide molecule, or two molecules of bilirubin, is compatible with our findings.

Displacement of Albumin-Bound Antimicrobial Agents by Bilirubin

The ability of bilirubin to displace antimicrobial agents from their binding sites on albumin was studied in vitro by equilibrium dialysis. Sulfonamides, tetracyclines, penicillins and cephalosporins of different degrees of protein binding were tested. It was found that bilirubin reduced the protein binding of all four classes of antimicrobial agents, although by varying degrees. This effect was most pronounced with the compounds which had the highest degree of protein binding, such as cloxacillin, cephazolin, methacycline and sulfisoxazole, all of which are bound greater than 80% by albumin. On the other hand, the drugs with less than 25% binding, such as ampicillin, cephalexine and tetracycline were not ostensibly displaced by bilirubin. Scatchard plots of the binding of sulfamethoxazole to albumin in the presence of 400 mumol/1 of bilirubin, showed that bilirubin almost completely displaced the sulfonamide molecule from the high affinity site on the albumin molecule. Reduced protein binding of drugs in hyperbilirubinemic infants may have pharmacokinetic significance.