Hydantoin Moieties Research Articles

Novel Mannich Bases Derived from 2-Substituted Benzimidazole and (Thio)Hydantoin Moieties as Potent Histone Deacetylase 6 (HDAC6) Inhibitors

Novel Mannich Bases Derived from 2-Substituted Benzimidazole and (Thio)Hydantoin Moieties as Potent Histone Deacetylase 6 (HDAC6) Inhibitors

Reactive Fibrous Materials for Decontamination of Chemical and Biological Threats

Polyamines are water-soluble polyelectrolytes with the amino groups that can be used to attach the polymers onto functional surfaces of fibrous materials. In addition, polyamines can be readily modified by (super) nucleophilic groups such as (alkyl) aminopyridines that enhance the polymer’s ability to promote hydrolysis of organophosphorous chemical warfare agents. Furthermore, attachment of hydantoin moieties augments the number of the imide, amide, or amine groups on the polyamine’s chain, which provides oxidizing properties to the resulting modified polyamine after halogenation. We report on polyamines with side chains modified to contain both (4-aminopyridine, APy) and 5-(4-hydroxybenzylidene) hydantoin (HBH) functionalities with enhanced content of the active bromine. Virucidal activity of the APy-and HBH-modified polyallylamine against human coronavirus (type 229E) was tested both in solution and on nylon-cotton fabric. The polymers appeared to be effective in inactivation of the coronavirus, at both low concentrations and short exposure times.

Tyrosine-derived novel antimicrobial hydantoin polymers: synthesis and evaluation of anti-bacterial activities

A new approach for the design and synthesis of cyclic N-halamine polymers having anti-bacterial activity based on a vinyl derivative of tyrosine-derived hydantoin is reported. The synthesis of N-halamine polymers generally involves the chemical modification of 5,5′-disubstituted hydantoin to introduce polymerizable vinyl moieties thereby restricting the halogen capture only on the amide nitrogen. Here we show the possibility of synthesizing vinyl monomers of N-halamine from α-amino acids wherein both the amide and imide nitrogens are available for halogen capture. Thus, a hydantoin monomer was synthesized from L-tyrosine and copolymerized with methyl methacrylate and 2-(hydroxyethyl)methacrylate, to obtain random co-polymers. The monomer and its co-polymers were characterized using NMR, IR, HRMS, GPC, DSC, EDAX and TGA analysis. Films of the co-polymers cast from 10% acetone solutions were exposed to sodium hypochlorite solution to activate the hydantoin moieties. The oxidative chlorine content of the films ranged from 0.6 to 0.9%. The activated films were exposed to both Gram positive (S. aureus) and Gram negative (E. coli) bacteria using standard protocols. Polymers having chlorine content as little as 0.6% exhibited 6 log reduction in the bacterial growth within 30 min of exposure. The method allows the halogenation of both amide and imide nitrogens and could be applied to the preparation of a number of vinyl hydantoins from many amino acids.

Synthesis and crystal structure of new heterocycles containing 1,2,4-oxadiazole, 1,2,4-oxadiazolone (thione), hydantoin, and mercaptobenzimidazole units.

A number of 1,2,4-oxadiazolone and mercapto nitro benzimidazole derivatives containing 1,2,4-oxadiazole and hydantoin moieties have been prepared, and their structures were identified by means of spectral/physical characteristics including X-ray diffraction data.

Macromol. Biosci. 12/2012

Back Cover: Novel degradable and antibacterial polymers are made by clicking hydantoin moieties to polycaprolactone. The degradability of polycaprolactone was retained and a fast antibacterial action towards Gram-negative and -positive cells was introduced thereby. Further details can be found in the article by L. Tan, S. Maji, C. Mattheis, Y. Chen, and S. Agarwal* on page 1721.

2H-chromene derivatives bearing thiazolidine-2,4-dione, rhodanine or hydantoin moieties as potential anticancer agents

A variety of (Z)-[(2H-chromen-3-yl)methylene]azolidinones 6a–t bearing thiazolidine-2,4-dione, rhodanine or hydantoin scaffolds were designed and synthesized as potential anticancer agents. Inhibitory effect of synthesized compounds 6a–t on the viability of cancer and non-cancer cells was assessed using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) reduction assay. The SAR study revealed that the N-substitution of azolidinone moiety cannot improve the activity but S/NH replacement (thiazolidine-2,4-dione/hydantoin) and S/O alteration (rhodanine/thiazolidine-2,4-dione) enable us to modulate the growth inhibition activity against various cell lines. Moreover, 6-bromo and 2-methyl substituents on chromene ring had positive effects on growth inhibitory activity depending on the tumor cell lines. Among the synthesized compounds, hydantoin derivative 6o with a 6-bromo-2-methyl-2H-chromene substructure showed the best profile of cytotoxicity comparable to that of cisplatin as standard anticancer agent.

Antimicrobial Hydantoin‐grafted Poly(ε‐caprolactone) by Ring‐opening Polymerization and Click Chemistry

Novel degradable and antibacterial polycaprolactone-based polymers are reported in this work. The polyesters with pendent propargyl groups are successfully prepared by ring-opening polymerization and subsequently used to graft antibacterial hydantoin moieties via click chemistry by a copper(I)-catalyzed azide-alkyne cycloaddition reaction. The well-controlled chemical structures of the grafted copolymers and its precursors are verified by FT-IR spectroscopy, NMR spectroscopy, and GPC characterizations. According to the DSC and XRD results, the polymorphisms of these grafted copolymers are mostly changed from semicrystalline to amorphous depending on the amount of grafted hydantoin. Antibacterial assays are carried out with Bacillus subtilis and two strains of Escherichia coli and show fast antibacterial action.

Synthesis and Structural Characterization of Spiro(fluorene-9,4′-imidazolidine)-2′,5′-dione and (9H-Fluorene-9-yl)urea

Alkaline hydrolysis of spiro(fluorene-9,4′-imidazolidine)-2′,5′-dione, 2 resulted in ring opening leading to (9H-fluorene-9-yl) urea, 3. The crystal structures 2 and 3 have been determined. Compound 2 crystallizes in the orthorhombic space group P212121 with a = 7.2596(9) A, b = 9.4497(14) A, c = 17.304(3) A and Z = 4 while compound 3 crystallizes in the monoclinic space group P21/c with a = 4.6171(3) A, b = 14.4713(9) A, c = 16.9762(14) A, β = 95.385(7)° and Z = 4. Both molecules have very similar bond lengths and angles pattern, even after the hydantoin ring opening. The 9H-fluorene moiety is nearly planar with rms of 0.007 and 0.032 A for 2 and 3. The angle between the mean planes of the 9H-fluorene and the hydantoin or carbamide moieties is 86.92(4)° and 71.07(4)° respectively. In both structures N–H···O hydrogen bonds connect molecules into the chains along a. The X-ray molecular structure and IR spectra for 2 and 3 are compared with those calculated by the density functional theory method. Alkaline hydrolysis of spiro(fluorene-9,4′-imidazolidine)-2′,5′-dione resulted in a ring opening product namely (9Н-fluorene-9-yl) urea.

Synthesis and Muscle Relaxant Activity of Two Analogues of Dantrolene Sodium in Mice

Dantrolene sodium (1) is a skeletal muscle relaxant that is known to act by preventing the release of calcium ions from the sarcoplasmic reticulum. Structure–activity studies of 1 have been limited to changes in the position or the nature of the nitro group, and replacement of the 4-nitrobenzene, furan, and hydantoin moieties with other rings, usually resulting in compounds with reduced or no activity. To investigate the influence of similarities in the electronic transmission ability of the furan nucleus of 5-aryl, 5-arylthio and 5-styryl-2-furancarboxaldehydes on biological activity, two corresponding analogues of 1 were prepared by the reaction of the respective aldehydes with 1-aminohydantoin and were evaluated by the rota-rod test in mice. Compared with 1 as standard, 1-[[[[5-(4-nitrobenzene)thio]-2-furanyl]-methylene] amino]-2,4-imidazolidinedione (2) exhibited higher activity, and 1-[[[[5-(4-nitrobenzene) ethenyl]-2-furanyl]-methylene]amino]-2,4-imidazolidinedione (3) showed comparable activity at 0.5, 3 and 6h after administration to mice. There is a correlation between the electronic transmission ability of the furan nucleus in compounds 1, 2 and 3 and muscle relaxant activity.

New photosensitive poly(amid‐imide)s containing chalcone moiety and hydantoin derivatives in the main chain: Synthesis and characterization

AbstractSix new poly(amid‐imide)s containing chalchone and hydantoin moieties in the main chain were synthesized through the polycondensation reaction of 1,3‐bis[4,4′‐bis(trimellityimido)phenyl]‐2‐propenone 6 with six hydantoin derivatives 7a‐f in a medium consisting of triphenyl phosphite, calcium chloride, pyridine, and N‐methyl‐2‐pyrrolidone. The polycondensation reaction produced a series of novel poly(amid‐imide)s 8a‐f in high yields with inherent viscosities between 0.26 and 0.42 dL/g. The resulting polymers were characterized by elemental analysis, viscosity measurements, solubility test, thermo gravimetric analysis (TGA and DTG), FTIR, and UV‐Vis spectroscopy. 1,3‐bis[4,4′‐bis(trimellityimido)phenyl]‐2‐propenone 6 was prepared from a three‐step reaction by using 4‐nitro benzaldehyde 1 and 4‐nitro acetophenone 2 as precursors. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009

Microwave-Assisted Synthesis of a New Hydantoin Monomer for Antibacterial Polymeric Materials

11-(4,4-Dimethyl-2,5-dioxoimidazolidin-1-yl)undecyl acrylate was synthesized in a two-step procedure using microwave irradiation. Poly(acrylates) containing fluorinated and hydantoin (5,5-dimethylimidazolidine-2,4-dione) moieties were prepared by free radical polymerization of 2-(perfluorooctyl)ethyl acrylate and the synthesized monomer with the aim of obtaining low surface energy polymeric materials with properties of contact-active biocides. Polymeric films were treated with a bleaching solution in order to convert the hydantoin units to N-halamines, well-known contact-active biocides. The reversibility of the chlorination reaction, necessary to impart a renewable biocide effect, was investigated by Fourier Transform-Attenuated Total Reflection. Preliminary biological tests conducted against Bacillus megaterium demonstrated the effective biocide properties of the prepared materials.

Synthesis and characterization of new flame‐retardant poly(amide‐imide)s containing phosphine oxide and hydantoin moieties in the main chain

AbstractSix new flame‐retardant poly(amide‐imide)s (PAIs) 9a–f with high inherent viscosities containing phosphine oxide and hydantoin moieties in main chain were synthesized from the polycondensation reaction of N,N′‐(3,3′‐diphenylphenylphosphine oxide) bistrimellitimide diacid chloride 7 with six hydantoin derivatives 8a–f by two different methods such as solution and microwave assisted polycondensation. Results showed that the microwave assisted polycondensation, by using a domestic microwave oven, proceeded rapidly, compared with solution polycondensation, and was completed in about 7–9 min. All of the obtained polymers were fully characterized by means of elemental analysis, viscosity measurements, solubility test, and FTIR spectroscopy. Thermal properties and flame retardant behavior of the PAIs 9a–f were investigated using thermal gravimetric analysis (TGA and DTG) and limited Oxygen index (LOI). Data obtained by thermal analysis (TGA and DTG) revealed that these polymers showed good thermal stability. Furthermore, high char yields in TGA and good LOI values indicated that these polymers are capable of exhibiting good flame retardant properties. These polymers can be potentially utilized in flame retardant thermoplastic materials. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102: 5062–5071, 2006

Four cycloalkanespiro-4′-imidazolidine-2′,5′-dithiones

The crystal structures of four cyclo­alkane­spiro-4′-imidazolidine-2′,5′-dithiones, namely cyclo­pentane­spiro-4′-imidazolidine-2′,5′-dithione {systematic name: 1,3-diaza­spiro­[4.4]­nonane-2,4-dithione}, C7H10N2S2, cyclo­hexane­spiro-4′-imidazolidine-2′,5′-dithione {systematic name: 1,3-diaza­spiro­[4.5]decane-2,4-dithione}, C8H12N2S2, cyclo­heptane­spiro-4′-imidazolidine-2′,5′-dithione {systematic name: 1,3-diaza­spiro­[4.6]undecane-2,4-dithione}, C9H14N2S2, and cyclo­octane­spiro-4′-imidazolidine-2′,5′-dithione {systematic name: 1,3-di­aza­spiro­[4.7]dodecane-2,4-dithione}, C10H16N2S2, have been determined. The three-dimensional packing in all of the structures is based on closely similar chains, in which hydantoin moieties are linked through N—H⋯S hydrogen bonding. The size of the cyclo­alkane moiety influences the degree of its deformation. In the cyclo­octane compound, the cyclo­octane ring assumes both boat–chair and boat–boat conformations.

Dimorphism in 3′-aminocyclohexanespiro-5′-hydantoin

The title compound [systematic name: 1'-aminocyclohexanespiro-4'-imidazole-2',5'(3'H,4'H)-dione], C8H13N3O2, has been synthesized and was found to crystallize in two different structures, both monoclinic and both with the same P2(1)/c space group. In the first structure, there are two molecules in the asymmetric unit, one of which uses all of its hydrogen-bond donors and acceptors and forms undulating layers, while the other forms chains propagating perpendicular to the layers. In the second structure, there is only one independent molecule and the packing is based on a chain structure mediated by hydrogen bonding between the hydantoin moieties and further grouped into hydrophilic layers separated by layers of the hydrophobic cyclohexyl groups.

New Optically Active Poly(amide–imide)s Containing N-Trimellitylimido-L-phenylalanine and Hydantoin Moieties: Synthesis and Properties

New Optically Active Poly(amide–imide)s Containing N -Trimellitylimido-L-phenylalanine and Hydantoin Moieties: Synthesis and Properties

New poly(amide imide)s containing bis(4‐trimellitimidophenyl) sulfone and hydantoin moieties in the main chain: Synthesis and properties

AbstractSeveral new poly(amide imide)s were synthesized through the polycondensation reactions of bis(4‐trimellitimidophenyl) sulfone [N,N′‐(4,4′‐diphenylsulfone) bistrimellitimide] with a number of hydantoin derivatives in a medium consisting of thionyl chloride, N‐methyl‐2‐pyrrolidone, and pyridine. The polycondensations produced a series of novel poly(amide imide)s in high yields with inherent viscosities of 0.20–0.46 dL/g. The resulting poly(amide imide)s were characterized with elemental analysis, viscosity measurements, thermogravimetric analysis, derivative thermogravimetry, solubility testing, and Fourier transform infrared spectroscopy. All the polymers were soluble at room temperature in polar solvents such as N,N‐dimethylacetamide, N,N‐dimethylformamide, dimethyl sulfoxide, tetrahydrofuran, and N‐methyl‐2‐pyrrolidone. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 96: 1776–1782, 2005

Hydantoin and hydrogen-bonding patterns in hydantoin derivatives.

The structure of hydantoin (imidazolidine-2,4-dione), C3H4N2O2, has been determined from a twinned crystal. The two carbonyl bond lengths are nearly equal, even though one of them adjoins electron-donating NH groups to either side while the other is adjacent to only one. Ab initio molecular-orbital calculations yield more negative Löwdin charge on the former than the latter. Hydantoin mol­ecules form two chains linked by N—H⋯O hydrogen bonds, from which inversion centres create a `chain of rings'. Out of 50 hydantoin moieties in 49 independent mol­ecules of hydantoin derivatives in the Cambridge Structural Database [Version 5.25; Allen (2002). Acta Cryst. B58, 380–388], five show this arrangement, six are a variant using the same O atom twice, five form a chain of edge-fused 12-membered hydrogen-bonded rings, and all but three of the remainder have one eight-membered ring and/or one chain connecting their hydantoin rings.

Synthesis and properties of new poly(amide imide)s containing trimellitic rings and hydantoin moieties in the main chain under microwave irradiation

AbstractTrimellitic anhydride was reacted with 4,4′‐diaminodiphenyl ether in a mixture of acetic acid and pyridine (3 : 2) at room temperature and was refluxed at 90–100°C, and N,N′‐(4,4′‐diphenylether) bistrimellitimide (3) was obtained in a quantitative yield. 3 was converted into N,N′‐(4,4′‐diphenylether) bistrimellitimide diacid chloride (4) by a reaction with thionyl chloride. Then, six new poly(amide imide)s were synthesized under microwave irradiation with a domestic microwave oven through the polycondensation reactions of 4 with six different derivatives of 5,5‐disubstituted hydantoin in the presence of a small amount of a polar organic medium such as o‐cresol. The polycondensation proceeded rapidly and was completed within 7–10 min, producing a series of new poly(amide imide)s in high yields with inherent viscosities of 0.27–0.66 dL/g. The resulting poly(amide imide)s were characterized by elemental analysis, viscosity measurements, differential scanning calorimetry, thermogravimetric analysis, derivative thermogravimetry, solubility testing, and Fourier transform infrared spectroscopy. All the polymers were soluble at room temperature in polar solvents such as N,N‐dimethylacetamide, N,N‐dimethylformamide, dimethyl sulfoxide, tetrahydrofuran, and N‐methyl‐2‐pyrrolidone. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 92: 3447–3453, 2004

Infrared characterization of biocidal nylon

Attenuated total reflectance Fourier transform infrared spectrometry has been employed to assess the degree of chlorination of hydantoin moieties which are covalently linked to the surface of the polyamide, Nylon 66. The N-chlorinated hydantoin functional groups are active in producing biocidal activity against pathogenic microorganisms upon direct contact with the surface molecules of the fabric. Chlorination of the treated Nylon 66 causes a blue shift of the hydantoin amide bands which can be conveniently monitored as a quality control procedure in the production of the biocidal fabric.

Hydantocidin: A new compound with herbicidal activity from Streptomyces hygroscopicus.

Hydantocidin, a new compound with potent non-selective herbicidal activity, was found in a submerged culture of Streptomyces hygroscopicus SANK 63584. It was isolated from the culture filtrate by the following successive treatments comprised of activated carbon, Diaion HP-20, Dowex 50WX4, and Avicel column chromatographies. Finally it was crystallized as colorless needles from acetone. The molecular formula, C7H10N2O6, was determined by analyses of HRFAB mass spectrum in conjunction with 13C NMR spectrometry. The structural elucidation revealed that it has a unique structure with a spiro-bond between ribose and hydantoin moieties in the molecule. The characteristic herbicidal activities against annuals as well as perennials, including monocotyledonous and dicotyledonous weeds, were observed.