Antimicrobial properties of highly fluorinated silver(I) tris(pyrazolyl)borates

Highly fluorinated tris(pyrazolyl)borate ligand [HB(3,5-(CF3)2Pz)3]- has been used in the isolation of air- and light-stable silver complex, [HB(3,5-(CF3)2Pz)3]Ag(OSMe2). It is a monomeric tetrahedral silver complex with an O-bonded dimethylsulfoxide ligand. The silver adduct [HB(3,5-(CF3)2Pz)3]Ag(OSMe2) and the related [HB(3,5-(CF3)2Pz)3] Ag(THF) (where OSMe2 = dimethyl sulfoxide; THF = tetrahydrofuran) show good antibacterial activity, and their antimicrobial efficacy against Staphylococcus aureus is greater than those of AgNO3 and silver sulfadiazine.     

Silver(I) complexes of fluorinated scorpionates: Ligand effects in silver catalyzed carbene insertion into C-H bonds in alkanes

Activation of C-H bonds of hydrocarbons via intermolecular carbene insertion has been investigated using tris(pyrazolyl)boratosilver(I) catalysts [MeB(3-(CF₃)Pz)₃]Ag(C₂H₄), [MeB(3-(C₂F₅)Pz)₃]Ag(C₂H₄) and [HB(3,5-(CF₃)₂Pz)₃]Ag(C₂H₄). Cyclopentane, 2-methylbutane, and 2,3-dimethylbutane were used as substrates. Carbenes derived from ethyl and tert-butyl diazoacetates have effectively been inserted into tertiary, secondary, as well as primary C-H bonds of hydrocarbons at room temperature using these catalysts. Tertiary C-H bonds in these substrates get preferentially activated over secondary C-H followed by primary C-H bonds. However, it is possible to increase the amount of primary C-H bond activated product by utilizing catalysts with increasingly acidic silver sites and sterically bulky tris(pyrazolyl)borate ligands. The carbene insertion into primary C-H bonds increases in the order: [MeB(3-(CF₃)Pz)₃]Ag(C₂H₄) < [MeB(3-(C₂F₅)Pz)₃]Ag(C₂H₄) < [HB(3,5-(CF₃)₂Pz)₃]Ag(C₂H₄). The carbene derived from tert-butyl diazoacetate with these catalysts shows slightly lower selectivity for primary C-H bonds compared to the ethyl diazoacetate-based carbene.     

Synthesis and spectroscopic investigations of four-coordinate nickel complexes supported by a strongly donating scorpionate ligand

Two four-coordinate nickel complexes, HB(^tBuIm)₃NiBr and HB(^tBuIm)₃NiNO, were prepared by reaction of a bulky tris(carbene)borate ligand with NiBr₂(PPh₃)₂ and NiBr(NO)(PPh₃)₂, respectively, and structurally and spectroscopically characterized. In addition to standard techniques, high-frequency and -field electron paramagnetic resonance (HFEPR) was employed to understand the spin triplet (S = 1) ground state of the bromo complex. HFEPR, combined with electronic absorption spectroscopy allows comparison of this novel complex with other paramagnetic four-coordinate Ni(II) species. The tris(carbene)borate ligand is a stronger σ-donor than corresponding tris(pyrazolyl)borates (traditional “scorpionate” ligands). The tris(carbene)borate ligand may also act as a π-acceptor, in contrast to tris(pyrazolyl)borates, which show relatively little π-bonding interactions. The influence of tris(carbene)borate substituents on the donor strength of the ligand have been elucidated from IR spectroscopic investigations of {NiNO}¹⁰ derivatives. HFEPR spectra of HB(^tBuIm)₃NiBr exhibit hyperfine coupling from Br, which indicates the strong electronic interaction between Ni(II) and this halide ligand, consistent with studies on tris(pyrazolyl)borate Ni(II) complexes.     

Copper complexes of imidazole-2-, pyrrole-2- and indol-3-carbaldehyde thiosemicarbazones: inhibitory activity against fungi and bacteria

Copper complexes of thiosemicarbazones of imidazole-2-carbaldehyde, pyrrole-2-carbaldehyde and indole-3-carbaldehyde were synthesised and characterised. The antimicrobial properties of the free ligands and their complexes were evaluated against yeasts, moulds and bacteria (Gram-positive and Gram-negative). Some copper chelates exhibited a moderate inhibitory activity, better than that of the corresponding free ligands. In particular, the pyrrole derivative [Cu(HL(2))(2)] proved to be a wide spectrum agent, showing an interesting inhibition of the growth of all Gram-positive bacteria and fungi tested at concentrations of 12-50 microg/mL. In contrast, a selective effect was observed for imidazole and indole chelates against fungi and Gram-positive bacteria, respectively.     

Synthesis and characterization of new copper(I) complexes containing 4-(diphenylphosphane)benzoic acid and "scorpionate" ligands with "in vitro" superoxide scavenging activity

New copper(I) complexes have been synthesised from the reaction of CuCl with 4-(diphenylphosphane)benzoic acid and lithium tris(1H-pyrazol-1-yl)methanesulfonate, Li(SO(3))C(pz)(3), sodium hydrotris(3-trifluoromethyl-1H-pyrazol-1-yl)borate, NaHB[3-(CF(3))pz](3), potassium dihydrobis(1H-1,2,4-triazol-1-yl)borate, KH(2)B(tz)(2), hydrotris(1H-1,2,4-triazol-1-yl)borate, KHB(tz)(3), sodium hydrotris(1H-pyrazol-1-yl)borate, NaHB(pz)(3), potassium hydrotris(3,5-dimethyl-1H-pyrazol-1-yl)borate KHB(3,5-Me(2)Pz)(3) or potassium hydrotris(4-bromo-1H-pyrazol-1-yl)borate KHB(4-Brpz)(3). The complexes obtained have been characterized by elemental analyses and FT-IR in the solid state, and by NMR (1H and 31P[(1)H]) spectroscopy and conductivity measurements in solution. The solution data are consistent with partial dissociation of the sterically hindered complexes by way of breaking of Cu-P and Cu-N bonds. Electrospray mass spectrometry has been used to investigate the relative properties of the 4-(diphenylphosphane)benzoic acid and of the "scorpionate" ligands towards copper(I) ions. Chemiluminescence technique was used to evaluate the superoxide scavenging activity of these new copper complexes.     

The introduction of l-phenylalanine into antimicrobial peptide protonectin enhances the selective antibacterial activity of its derivative phe-Prt against Gram-positive bacteria

Protonectin was a typical amphiphilic antimicrobial peptide with potent antimicrobial activity against Gram-positive and Gram-negative bacteria. In the present study, when its eleventh amino acid in the sequence was substituted by phenylalanine, the analog named phe-Prt showed potent antimicrobial activity against Gram-positive bacteria, but no antimicrobial activity against Gram-negative bacteria, indicating a significant selectivity between Gram-positive bacteria and Gram-negative bacteria. However, when Gram-negative bacteria were incubated with EDTA, the bacteria were susceptible to phe-Prt. Next, the binding effect of phe-Prt with LPS was determined. Our result showed that LPS could hamper the bactericidal activity of phe-Prt against Gram-positive bacteria. The result of zeta potential assay further confirmed the binding effect of phe-Prt with LPS for it could neutralize the surface charge of E. coli and LPS. Then, the effect of phe-Prt on the integrity of outer membrane of Gram-negative bacteria was determined. Our results showed that phe-Prt had a much weaker disturbance to the outer membrane of Gram-negative bacteria than the parent peptide protonectin. In summary, the introduction of l-phenylalanine into the sequence of antimicrobial peptide protonectin made phe-Prt show significant selectivity against Gram-positive bacteria, which could partly be attributed to the delay effect of LPS for phe-Prt to access to cell membrane. Although further study is still needed to clarify the exact mechanism of selectivity, the present study provided a strategy to develop antimicrobial peptides with selectivity toward Gram-positive and Gram-negative bacteria.

     

Isolation and phylogenetic analysis of bacteria with antimicrobial activities from the Mediterranean sponges Aplysina aerophoba and Aplysina cavernicola

The aim of this study was to isolate bacteria with antimicrobial activities from the marine sponges Aplysina aerophoba and Aplysina cavernicola. The obtained 27 isolates could be subdivided into eight phylogenetically different clusters based on comparative sequence analysis of their 16S rDNA genes. The sponge isolates were affiliated with the low (Bacillus) and high G+C Gram-positive bacteria (Arthobacter, Micrococcus), as well as the alpha-Proteobacteria (unknown isolate) and gamma-Proteobacteria (Vibrio, Pseudoalteromonas). One novel Bacillus species was identified and two species were closely related to previously uncharacterized strains. Isolates with antimicrobial activity were numerically most abundant in the genera Pseudoalteromonas and the alpha-Proteobacteria. The sponge isolates show antimicrobial activities against Gram-positive and Gram-negative reference strains but not against the fungus Candida albicans. A general pattern was observed in that Gram-positive bacteria inhibited Gram-positive strains while Gram-negative bacteria inhibited Gram-negative isolates. Antimicrobial activities were also found against clinical isolates, i.e. multi-resistant Staphylococcus aureus and Staphylococcus epidermidis strains isolated from hospital patients. The high recovery of strains with antimicrobial activity suggests that marine sponges represent an ecological niche which harbors a hitherto largely uncharacterized microbial diversity and, concomitantly, a yet untapped metabolic potential.     

Antimicrobial properties of phenolic compounds from berries

AIMS: To investigate the antimicrobial properties of phenolic compounds present in Finnish berries against probiotic bacteria and other intestinal bacteria, including pathogenic species. METHODS AND RESULTS: Antimicrobial activity of pure phenolic compounds representing flavonoids and phenolic acids, and eight extracts from common Finnish berries, was measured against selected Gram-positive and Gram-negative bacterial species, including probiotic bacteria and the intestinal pathogen Salmonella. Antimicrobial activity was screened by an agar diffusion method and bacterial growth was measured in liquid culture as a more accurate assay. Myricetin inhibited the growth of all lactic acid bacteria derived from the human gastrointestinal tract flora but it did not affect the Salmonella strain. In general, berry extracts inhibited the growth of Gram-negative but not Gram-positive bacteria. These variations may reflect differences in cell surface structures between Gram-negative and Gram-positive bacteria. Cloudberry, raspberry and strawberry extracts were strong inhibitors of Salmonella. Sea buckthorn berry and blackcurrant showed the least activity against Gram-negative bacteria. CONCLUSION: Different bacterial species exhibit different sensitivities towards phenolics. SIGNIFICANCE AND IMPACT OF THE STUDY: These properties can be utilized in functional food development and in food preservative purposes.     

Inhibitory and antimicrobial activities of OGTI and HV-BBI peptides, fragments and analogs derived from amphibian skin

A series of linear and cyclic fragments and analogs of two peptides (OGTI and HV-BBI) isolated from skin secretions of frogs were synthesized by the solid-phase method. Their inhibitory activity against several serine proteinases: bovine β-trypsin, bovine α-chymotypsin, human leukocyte elastase and cathepsin G from human neutrophils, was investigated together with evaluation of their antimicrobial activities against Gram-negative bacteria (Escherichia coli) and Gram-positive species isolated from patients (Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus sp., Streptococcus sp.). The cytotoxicity of the selected peptides toward an immortal human skin fibroblast cell line was also determined. Three peptides: HV-BBI, its truncated fragment HV-BBI(3-18) and its analog [Phe(8)]HV-BBI can be considered as bifunctional compounds with inhibitory as well as antibacterial properties. OGTI, although it did not display trypsin inhibitory activity as previously reported in the literature, exerted antimicrobial activity toward S. epidermidis. In addition, under our experimental conditions, this peptide did not show cytotoxicity.     

Nanoparticles functionalized with ampicillin destroy multiple-antibiotic-resistant isolates of Pseudomonas aeruginosa and Enterobacter aerogenes and methicillin-resistant Staphylococcus aureus

We show here that silver nanoparticles (AgNP) were intrinsically antibacterial, whereas gold nanoparticles (AuNP) were antimicrobial only when ampicillin was bound to their surfaces. Both AuNP and AgNP functionalized with ampicillin were effective broad-spectrum bactericides against Gram-negative and Gram-positive bacteria. Most importantly, when AuNP and AgNP were functionalized with ampicillin they became potent bactericidal agents with unique properties that subverted antibiotic resistance mechanisms of multiple-drug-resistant bacteria.     

Antimicrobial activities of black-pigmented Gram-negative anaerobes

Abstract The antimicrobial activities of Prevotella intermedia and Porphyromonas gingivalis isolates were tested against other species of Gram-positive and Gram-negative anaerobes as well as against each other. Generally, Pr. intermedia possessed significantly higher antimicrobial activity than P. gingivalis . The strongest activity of P. gingivalis towards Gram-negative anaerobes was directed against Pr. intermedia . Cross-sensitivity between both species was observed with strains from different lesions. Antimicrobial activity towards strains of the same species was detected only with Pr. intermedia . No correlations were found between plasmid content and antimicrobial activity. It was concluded that the inhibitory potency of Pr. intermedia could be one reason for the high proportion of black-pigmented Gram-negative anaerobes in the subgingival flora of periodontitis lesions.     

Purification and properties of antimicrobial peptides from skin secretions of the Eritrea clawed frog Xenopus clivii (Pipidae)

Five peptides with antimicrobial activity were isolated from norepinephrine-stimulated skin secretions of the tetraploid frog Xenopus clivii Peracca, 1898 (Pipidae). Characterization of the peptides demonstrated that they are structurally similar to magainins (2 peptides), caerulein-precursor fragments, CPF (2 peptides), and xenopsin-precursor fragments, XPF (1 peptide) that have been previously isolated from other species of the genus Xenopus. The magainins and the XPF peptide were active only against the Gram-negative microorganism Escherichia coli whereas the CPF peptides were also active against the Gram-positive Staphylococcus aureus. The most abundant antimicrobial peptide in the secretions, CPF-C1 (GFGSLLGKALRLG ANVL.NH(2)) inhibited the growth of the Gram-negative bacteria Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa (MIC≤25μM) suggesting potential for development into an anti-infective agent for use against these emerging antibiotic-resistant pathogens.     

Syntheses and spectroscopic and structural characterization of silver(I) complexes containing tris(isobutyl)phosphine and poly(azol-1-yl)borates

Silver(I) derivatives [Ag(L)(PⁱBu₃)] (L = H₂B(tz)₂ (dihydrobis(1H-1,2,4-triazol-1-yl)borate), HB(tz)₃ (hydrotris(1H-1,2,4-triazol-1-yl)borate), Tp (hydrotris(1H-pyrazol-1-yl)borate), Tp∗ (hydrotris(3,5-dimethyl-1H-pyrazol-1-yl)borate), Tp^Me (hydrotris(3-methyl-1H-pyrazol-1-yl)borate), Tp^CF3 (hydrotris(3-trifluoromethyl-1H-pyrazol-1-yl)borate), Tp^4Br (hydrotris(4-bromo-1H-pyrazol-1-yl)borate), HB(btz)₃ (hydrotris(1H-1,2,4-benzotriazol-1-yl)borate), Tm (hydrotris(3-methy-1-imidazolyl-2-thione)borate), pzTp (tetrakis(1H-pyrazol-1-yl)borate), pz⁰Tp^Me (tetrakis(3-methyl-1H-pyrazol-1-yl)borate) have been synthesized from the reaction of [Ag(NO₃)(PⁱBu₃)₂] with ML (M = Na or K) and characterized both in solution (¹H- and ³¹P{¹H} NMR, ESI MS spectroscopy, conductivity) and in the solid state (IR, single crystal X-ray structure analysis). These complexes are air-stable and light-sensitive and non-electrolytes in CH₂Cl₂ and acetone in which they slowly decompose, even with the strict exclusion of oxygen and light, yielding metallic silver and/or azolate (Az) species of formula [Ag(Az)(PⁱBu₃)_x] upon breaking of the bridging B-N_(azole) bond. The solid state structures of [Ag(Tp)(PⁱBu₃)], [Ag(Tp^Me)(PⁱBu₃)], [Ag(Tp^CF3)(PⁱBu₃)], [Ag{HB(btz)₃}(PⁱBu₃)], and [Ag(Tm)(PⁱBu₃)] show that the silver atom adopts a distorted tetrahedral coordination geometry. [Ag(L)(PPh₃)] can be easily obtained from the reaction of [Ag(L)(PⁱBu₃)] with excess PPh₃, whereas from the reverse reaction of [Ag(L)(PPh₃)] with PⁱBu₃a mixture of [Ag(L)(PⁱBu₃)] and [Ag(L)]₂ and [Ag(L)(PPh₃)] was recovered. ³¹P{¹H} NMR variable temperature NMR studies showed that in the pz⁰Tp^x derivatives the scorpionate ligand acts as a bidentate donor, whereas tridentate coordination is found for all tris(azolyl)borate derivatives, both in solution and in the solid state. ESI MS data suggest the existence in solution of species such as [Ag(PⁱBu₃)₂]⁺ upon dissociation of the L ligand, and also the formation of dimeric species of the form [Ag₂(L)(PⁱBu₃)₂]⁺.     

Development of a Gram-negative selective agar (GNSA) for the detection of Gram-negative microflora in sputa in patients with cystic fibrosis

AIMS: To develop a selective agar medium to help detect and quantify Gram-negative flora in the sputum of patients with cystic fibrosis (CF). METHODS AND RESULTS: A novel Gram-negative Selective Agar (GNSA) medium was developed consisting of tryptone soya broth (30 g), bacteriological agar no.1 (10 g), yeast extract (5 g), crystal violet (2 mg), nisin (48 mg), novobiocin (5 mg), cycloheximide (100 mg), amphotericin (2 mg) and double distilled water (1 l), for the selective culture of all Gram-negative flora from the sputum of patients with CF. GNSA was able to support the proliferation of all 34 Gram-negative organisms examined, including 23 species most commonly associated with CF, but was unable to support the growth of the 12 Gram-positive or seven fungal organisms examined. Sensitivity studies demonstrated that the GNSA medium was able to detect not less than 1.50 x 102 CFU ml-1 sputum Pseudomonas aeruginosa, 2.38 x 102 CFU ml-1 sputum Burkholderia cepacia genomovar IIIb and 6.70 x 103 CFU ml-1 sputum Stenotrophomonas maltophilia. A comparison of the microbial flora detected in the sputa of 12 adult CF patients by employment of routine bacteriological agar media and GNSA, demonstrated that GNSA was able to detect all Gram-negative organisms cultured by routine media, but had the advantage of detecting Alcaligenes xylosoxidans in two CF patients, whom had no previous history of Gram-negative infection. CONCLUSIONS: GNSA was unable to support the proliferation of any Gram-positive organism or yeast/fungi, but was successful in supporting the growth of all Gram-negative organisms challenged. SIGNIFICANCE AND IMPACT OF THE STUDY: Employment of this medium coupled with semi-automated technology may aid in helping to efficiently determine Gram-negative loading of respiratory secretions, particularly in response to antibiotic intervention.     

Antimicrobial properties of the frog skin peptide, ranatuerin-1 and its [Lys-8]-substituted analog

The predicted conformation of ranatuerin-1 (SMLSVLKNLG(10)KVGLGFVACK(20)INK QC), an antimicrobial peptide first isolated from the skin of the bullfrog Rana catesbeiana, comprises three structural domains: alpha-helix (residues 1-8), beta-sheet (residues 11-16) and beta-turn (residues 20-25). Circular dichroism studies confirm significant alpha-helical character in 50% trifluoroethanol. Replacement of Cys-19 and Cys-25 by serine resulted only in decreased antimicrobial potency but deletion of either the cyclic heptapeptide region [residues (19-25)] or the N-terminal domain [residues (1-8)] produced inactive analogs. Substitution of the glycine residues in the central domain of the [Ser-19, Ser-25] analog by lysine produced inactive peptides despite increased alpha-helical content and cationicity. The substitution Asn-8-->Lys gave a ranatuerin-1 analog with increased alpha-helicity and cationicity and increased potency against a range of Gram-positive and Gram-negative bacteria and against C. albicans but only a small increase (21%) in hemolytic activity. In contrast, increasing alpha-helicity and hydrophobicity by the substitution Asn-22-->Ala resulted in a 3.5-fold increase in hemolytic activity. Effects on antimicrobial potencies of substitutions of neutral amino acids at positions 4, 18, 22, and 24 by lysine were less marked. Strains of pathogenic E. coli from different groups showed varying degrees of sensitivity to ranatuerin-1 (MIC between 5 and 40 microM) but [Lys-8] ranatuerin-1 showed increased potency (between 2- and 8-fold; P < 0.01) against all strains. The data demonstrate that [Lys-8] ranatuerin-1 shows potential as a candidate for drug development.     

Design and synthesis of spiro[indole-thiazolidine]spiro[indole-pyrans] as antimicrobial agents

A series of novel spiro[indole-thiazolidine]spiro[indole-pyran] derivatives were synthesized from N-(bromoalkyl)indol-2,3-diones via monospiro-bisindole intermediates; the two indole nuclei being connected via N-(CH(2))(n)-N linker. Synthesized compounds were evaluated for their antimicrobial activities in vitro against three Gram-positive bacteria (Staphylococcus aureus, Bacillus subtilis, and Staphylococcus epidermis), four Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Salmonella typhi, and Klebsiella pneumonia) as well as four fungi (Aspergillus niger, Aspergillus fumigatus, Aspergillus flavus, and Candida albicans) using Cup plate method. Bis spiro-indoles exhibited stronger antibacterial and antifungal efficiency than their corresponding mono spiro-indoles. Compound 10e, the most active derivative was shown to inhibit the growth of all bacterial strains and two fungal strains (A. niger and C. albicans).     

The influence of silver content on antimicrobial activity and color of cotton fabrics functionalized with Ag nanoparticles

The aim of this study was to examine the antimicrobial efficiency and color changes of cotton fabrics loaded with colloidal silver nanoparticles which were synthesized without using any stabilizer. The influence of colloidal concentration and consequently, the amount of silver deposited onto the fabric surface, on antimicrobial activity against Gram-negative bacterium Escherichia coli, Gram-positive bacterium Staphylococcus aureus and fungus Candida albicans as well as laundering durability of obtained effects were studied. Although cotton fabrics loaded with silver nanoparticles from 10 ppm colloid exhibited good antimicrobial efficiency, their poor laundering durability indicated that higher concentrated colloids (50 ppm) must be applied for obtaining long-term durability. Additionally, the influence of dyeing with C.I. Direct Red 81 on antimicrobial activity of cotton fabrics loaded with silver nanoparticles as well as the influence of their presence on the color change of dyed fabrics were evaluated. Unlike color change, the antimicrobial efficiency was not affected by the order of dyeing and loading of silver nanoparticles.     

In vitro and in vivo antimicrobial activity of two alpha-helical cathelicidin peptides and of their synthetic analogs

Two alpha-helical antimicrobial peptides (BMAP-27 and -28) and four synthetic analogs were compared for in vitro and in vivo antimicrobial efficacy. All peptides proved active in vitro at micromolar concentrations against a range of clinical isolates, including antibiotic-resistant strains. BMAP-27 and two analogs were more effective towards Gram-negative, and BMAP-28 towards Gram-positive organisms. In addition, BMAP-28 provided some protection in vitro against human herpes simplex virus type 1 (HSV-1). The parent peptides and mBMAP-28 analog protected mice from lethal i.p. infections in an acute peritonitis model at peptide doses significantly lower than those toxic to the animals, suggesting a satisfactory therapeutic index.     

Heteroleptic κ(N,C)-2-phenylpyridine platinum complexes: The use of bis(pyrazolyl)borates as ancillary ligands

Luminescent platinum(II) bis(pyrazolyl)borate complexes bearing orthometalated phenylpyridines (based on 2-phenylpyridine, 3-hexyloxy-2-phenylpyridine and (4-(pyridine-2-yl)-phenyl)methanol) and bis(pyrazolyl)borate ligands (employed as potassium dihydridobis(pyrazolyl)borate and potassium dihydridobis(3,5-dimethylpyrazolyl)borate) have been synthesized and characterized. By reaction of K₂PtCl₄ with phenylpyridine ligands a precursor has been obtained which was further converted to the corresponding heteroleptic complexes. All platinum(II) bis(pyrazolyl)borate complexes have been investigated by nuclear magnetic resonance, Fourier transform infrared spectroscopy, thermal analysis and UV-Vis absorption spectroscopy. Luminescence as well as lifetime measurements in solution and in the solid state have been performed to establish a qualitative relationship between structure and luminescence properties. The absorption and emission properties of these complexes are governed by the nature of the orthometalating ligand with emission maxima ranging from 488 to 551 nm. Emission spectra at room temperature show well-resolved vibronic fine structures and a strong spin-orbit coupling. For the compounds under investigation the mixing of the excited states leads to apparent lifetimes in the microsecond regime (5.7-8.6 μs), rendering these materials phosphorescent.     

In vitro activity of ramoplanin and comparator drugs against anaerobic intestinal bacteria from the perspective of potential utility in pathology involving bowel flora

Susceptibility of intestinal bacteria to various antimicrobial agents in vitro, together with levels of those agents achieved in the gut, provides information on the likely impact of the agents on the intestinal flora. Orally administered drugs that are poorly absorbed may be useful for treatment of intestinal infections and for certain other situations in which intestinal bacteria may play a role. The antimicrobial activity of ramoplanin (MDL 62,198) against 928 strains of intestinal anaerobic bacteria was determined using the NCCLS-approved Wadsworth brucella laked-blood agar dilution method. The activity of ramoplanin was compared with that of ampicillin, bacitracin, metronidazole, trimethoprim/sulfamethoxazole (TMP/SMX), and vancomycin. The organisms tested included Bacteroides fragilis group (n=89), other Bacteroides species (n=16), other anaerobic Gram-negative rods (n=56) anaerobic cocci (n=114), Clostridium species (n=426), and non-sporeforming anaerobic Gram-positive rods (n=227). The overall MIC(90)s of ramoplanin, ampicillin, bacitracin, metronidazole, and vancomycin were 256, 32, 128, 16, and 128 mcg/ml, respectively. Ramoplanin was almost always highly active vs. Gram-positive organisms and relatively poor in activity against Gram-negative organisms, particularly Bacteroides, Bilophila, Prevotella, and Veillonella. Vancomycin was quite similar to ramoplanin in its activity. Ampicillin was relatively poor in activity vs. organisms that often produce beta-lactamase, including most of the Gram-negative rods as well as Clostridium bolteae and C. clostridioforme. Bacitracin was relatively poor in activity against most anaerobic Gram-negative rods, but better vs. most Gram-positive organisms. Metronidazole was very active against all groups other than bifidobacteria and some strains of other types of non-sporeforming Gram-positive bacilli. TMP/SMX was very poorly active, with an MIC(90) of >2048 mcg/ml.