Tautomeric Isomers Research Articles

Synthesis, conformational analysis and antimicrobial activity of 10-benzyl-1,2,4-triazolo[4,3-b]1,2,4-triazino[5,6-b]indole acyclo C-nucleoside analogs

Condensation of 5-benzyl-3-hydrazino-1,2,4-triazino[5,6-b]indole with various sugar aldoses or ketoses gave the corresponding sugar hydrazones as single geometrical isomer or exist in E/Z tautomeric isomers. The hydrazones underwent heterocyclization with Fe(Ш)Cl3 to give the N2-adduct acyclo C-nucleosides: 3-(alditol-1yl)-10-benzyl-1,2,4-triazolo[4,3-b]1,2,4-triazino[5,6-b]indoles rather than the N4-adduct: 10-(alditol-1-yl)-3-benzyl-1,2,4-triazolo[3,4-c]1,2,4-triazino[5,6-b] indoles on the basis of chemical and UV spectral proofs. Conformational analysis of their polyacetates were studied. The new acyclo C-nucleosides were evaluated for antimicrobial activity.

Histidine tautomerism-mediated transthyretin amyloidogenesis: A molecular insight

Characterization of the conformational alterations involved in monomer misfolding is essential for elucidating the molecular basis of the initial stage of protein accumulation. Here, we report the first structural analyses of transthyretin (TTR) (26−57) fragments with two histidine tautomeric states (δ; Nδ1H and ε; Nε2H) using replica-exchange molecular dynamics (REMD) simulations. Explaining the organizational properties and misfolding procedure is challenging because the δ and ε configurations can occur in the free neutral state. REMD revealed that β-sheet generation is favored for the δδ (16.8%) and εδ (6.7%) tautomeric isomers, showing frequent main-chain contacts between the stable regions near the head (N-terminus) and central (middle) part compared to the εε (4.8%) and δε (2.8%) isomers. The presence of smaller and wider local energy minima may be related to the structural stability and toxicity of δδ/εδ and εε/δε. Histidines31 and 56 were the parts of regular (such as β-strand) and nonregular (such as coil) secondary structures within the highly toxic TTR isomer. For TTR amyloidosis, focusing on hazardous isomeric forms with high sheet contents may be a potent treatment strategy. Overall, our findings support the tautomerism concept and aid in our comprehension of the basic tautomeric actions of neutral histidine throughout the misfolding process.

Mechanistic insights into the conformational switch in profilin-1 subject to collective effects of mutation and histidine tautomerism

Mutations and histidine (His) tautomerism in profilin-1 (PFN1) are associated with amyotrophic lateral sclerosis (ALS). The conformational changes in PFN1 caused by the collective effects of G117V mutation and His tautomeric isomers εε, εδ, δε, and δδ were clarified using molecular dynamics (MD) simulations. The predominant structural variations were seen in α-helices, β-sheets, turns, and coils and the His tautomer's unique degree of disruption was seen in these conformations. The content of α-helices was 23.2 % in the εε and δδ isomers, but the observed α-helices in the isomers εδ and δε were 20.3 % and 21.7 % respectively. The percentage of β-sheet was found to be higher (34.1) in the εε isomer than in the εδ, δε, and δδ isomers, and the values were 30.4, 29.7, and 31.9, respectively. Intermolecular water dynamics analysis discloses that His 133 can form an intramolecular H-bond interaction (Nα-H---Nδ), confirming the experimental observations in the simulations of εε, δε, and δδ isomers of G117V PFN1 mutant. It was concluded that these solvent molecules are crucial for aggregation and must be considered in future research on the PFN1 associated with ALS. Overall, the study offers a thorough microscopic understanding of the pathogenic mechanisms behind conformational changes that cause aggregation illnesses like ALS.

Exposure to the electric field: A potential way to block the aggregation of histidine tautomeric isomers of β-amyloid

Controlling protein misfolding and accumulation in neurodegeneration is a challenge in chemical neuroscience. The application of appropriate electric fields (EFs) can be a potential noninvasive therapy to treat neuro disorders. The effect of EFs of varying intensities and directions on the conformational dynamics of β-Amyloid40 (Aβ40) under histidine tautomerism has been investigated for the first time. Our findings suggest that peptides tend to align their dipole moments with the orientation of EF. Irrespective of the EF direction, the dipole moment magnitude is affected by the EF strength. With the conformational changes, the EF strength equal to 0.5 V/nm destroyed the β-sheet content of the δδδ isomer as a potentially toxic agent. The content of the alpha-helical structure which can be transformed into the β-sheet is reduced. The strength of the EF showed a significant influence on the reduction of the number of intra-protein hydrogen bonds especially when EF is equal to 0.5 V/nm which could facilitate destabilization of the structure of the peptides. Current findings provide quantitative insights into the tautomerization-mediated Aβ40 dynamic and conformational changes induced by the external EFs in aqueous solutions, which may provide beneficial information for use as a therapeutic technique.

Histidine tautomerism dependent conformational transitions driven aggregation of profilin-1: Implications in amyotrophic lateral sclerosis

Aggregation of profilin-1 (PFN1) causes a fatal neurodegenerative disease, familial amyotrophic lateral sclerosis (fALS). Histidine (His) tautomerism has been linked to the formation of fibril aggregation causing neurodegenerative disease. Characterization of intermediate species that form during aggregation is crucial, however, this has proven very challenging for experimentalists due to their transient nature. Hence, molecular dynamics (MD) simulations have been performed on the His tautomeric isomers εε, εδ, δε, and δδ of PFN1 to explain the structural changes and to correlate them with its aggregation propensity. MD simulations show that His133 presumably plays a major role in the aggregation of PFN1 upon His tautomerism compared to His119. Further, the formation of a new 310-helix is observed in εε and δε but 310-helix is not observed in δδ and εδ isomers. In addition, our findings unveil that β-sheet dominating conformations are observed in His119(δ)-His133(δ) δδ isomer of PFN1 with significant antiparallel β-sheets between residues T15-G23, S29-A33, L63-L65, Q68-S76, F83-T89, T97-T105, and K107-K115, suggesting a novel aggregation mechanism possibly occur for the formation of PFN1 aggregates. Overall, these results propose that MD simulations of PFN1 His tautomers can provide a detailed microscopic understanding of the aggregation mechanisms which are hard to probe through experiments.

Mechanistic Insights into the Polymorphic Associations and Cross-Seeding of Aβ and hIAPP in the Presence of Histidine Tautomerism: An All-Atom Molecular Dynamic Study.

Hundreds of millions of people around the world have been affected by Type 2 diabetes (T2D) which is a metabolic disorder. Clinical research has revealed T2D as a possible risk factor for Alzheimer’s disease (AD) development (and vice versa). Amyloid-β (Aβ) and human islet amyloid polypeptide are the main pathological species in AD and T2D, respectively. However, the mechanisms by which these two amyloidogenic peptides co-aggregate are largely uninvestigated. Herein, for the first time, we present the cross-seeding between Amylin1-37 and Aβ40 considering the particular effect of the histidine tautomerism at atomic resolution applying the all-atom molecular dynamics (MD) simulations for heterodimeric complexes. The results via random seed MD simulations indicated that the Aβ40(δδδ) isomer in cross-talking with Islet(ε) and Islet(δ) isomers could retain or increase the β-sheet content in its structure that may make it more prone to further aggregation and exhibit higher toxicity. The other tautomeric isomers which initially did not have a β-sheet structure in their monomeric forms did not show any generated β-sheet, except for one seed of the Islet(ε) and Aβ40(εεε) heterodimers complex that displayed a small amount of formed β-sheet. This computational research may provide a different point of view to examine all possible parameters that may contribute to the development of AD and T2D and provide a better understanding of the pathological link between these two severe diseases.

Infrared spectroscopic and density functional theoretical study on the binary rhodium–oxygen Rh2O9+ cation

The mass-selected dirhodium oxide Rh2O9+ was prepared from the reaction of laser ablation of rhodium atoms with O2/He mixtures. Infrared spectra of Rh2O9+ are measured by infrared photodissociation spectroscopy in the rhodium-oxygen and OO stretching frequency region observed at 1254, 876 and 1536 cm−1. To assign the experimental spectra, total 43 tautomeric isomers with doublet, quartet, sextet and octet states are optimized and analyzed to compare the experimental with simulated spectra derived from density functional calculations. Further CCSD(T) single point energy confirmed the most stable isomer was the dinuclear sextet Rh2O9+ cation with a pseudo five-numbered ring as well as one Rh-O-Rh core terminally bonded to one superoxide, two terminal Rh-O, and two dioxygen groups. The three observed bands at 876, 1254 and 1536 cm−1 bands are exactly assigned to the terminal Rh-O, superoxide OO and weak dioxygen OO stretching modes compared to calculated vibration frequencies of the sextet Rh2O9+ cation(isolmer 29). Bonding analysis indicate that both rhodium of the Rh2O9+ cation observed display + 5 and + 3 formal oxidation state, respectively.

Intrinsic Origin of Tau Protein Aggregation: Effects of Histidine Tautomerism on Tau267-312 Monomer.

Histidine tautomerism is considered a crucial component that affects the constitutional and accumulation characteristics of the tau267-312 monomer in the neutral condition, which are connected with the pathobiology of Alzheimer's disease (AD). Interpreting the organizational characteristics and accumulation procedure is a challenging task because two tautomeric conformations (the Nε-H or Nδ-H tautomer) can occur in the open neutral condition. In the current work, replica-exchange molecular dynamics (REMD) simulations were performed to investigate the structural properties of the tau267-312 monomer considering the histidine tautomeric effect. Based on the simulation outcomes, the histidine 268 (H268) (δ)-H299 (δ) (δδ) isomer had the highest β-sheet content with a value of 26.2%, which acquires a sheet-governing toxic conformer with the first abundant conformational state of 22.6%. In addition, δδ displayed notable antiparallel β-sheets between lysine 8 (K8)-asparagine 13 (N13) and valine 40 (V40)-tyrosine 44 (Y44) as well as between K32-H33 and V40-Y44 (β-meander supersecondary structure), indicating this tautomeric isomer may exist to stimulate tau oligomerization. Furthermore, H299 was found to play an essential role in the structural stabilization of the δδ isomer compared with H268. The present research will aid in obtaining insight into the organizational and accumulation properties of tau protein in the presence of histidine tautomerism to control AD.

Tautomeric Effect of Histidine on the Monomeric Structure of Amyloid β-Peptide(1-42).

Tautomeric state of histidine is one of the factors that influence the structural and aggregation properties of amyloid β (Aβ)-peptide in neutral state. It is worth it to uncover the monomeric properties of Aβ(1-42) peptide in comparison with Aβ(1-40) peptide. Our replica-exchange molecular dynamics simulations results show that the sheet content of each tautomeric isomer in Aβ(1-42) monomer is slightly higher than that in Aβ(1-40) monomer except His6(δ)-His13(δ)-His14(δ) (δδδ) isomer, implying higher aggregation tendency in Aβ(1-42), which is in agreement with previous experimental and theoretical studies. Further analysis indicates that (εεε), (εδε), (εδδ), and (δδε) isomers prefer sheet conformation although they are in nondominating states. Particularly, it is confirmed that antiparallel β-sheets of (εδδ) were formed at K16-E22 (22.0-43.9%), N27-A30 except G29 (21.9-40.2%), and M35-I41 except G37 (24.1-43.4%). Furthermore, (εδδ) may be the easiest one to overcome structural transformation due to nonobstructing interactions between K16 and/or L17 and histidine residues. The current study will help to understand the tautomeric effect of Aβ(1-42) peptide to overcome Alzheimer's disease.

Infrared Spectroscopic Study of the Adsorption Forms of Cyanuric Acid and Cyanuric Chloride on TiO2

Cyanuric acid is often found to be the end product in the hydrolysis of waste melamine and in the TiO2-mediated photocatalytic decomposition of s-triazine-containing compounds used as herbicides or dyes. The photocatalytically recalcitrant nature of cyanuric acid on TiO2 may be closely related to its adsorption properties, including the tautomeric forms present on the surfaces and their bonding structures, which remain to be determined. In this paper, we present the optimized adsorption structures of the four tautomeric isomers (triketo, diketo, monoketo, and triol) of cyanuric acid on a model rutile-TiO2(110) surface and their vibrational absorptions. Experimentally, the adsorption structures of cyanuric acid and chloride on powdered TiO2 are analyzed on the basis of the theoretically obtained, characteristic infrared information. Cyanuric acid on TiO2 at 35 °C exists in triketo and hydroxylated forms, but the diketo becomes the predominant form on the surface at 250 °C, being bonded to a titanium site via one of its carbonyl groups and with a N-H···O hydrogen bonding interaction. Hydroxylation of cyanuric chloride occurs as it is adsorbed on TiO2 at 35 °C. Upon being heated to 200 °C, the surface is mainly covered with the diketo form of cyanuric acid after the adsorption of cyanuric chloride.

Molecular structure investigation and tautomerism aspects of (E)-3-benzylideneindolin-2-one

The synthesis and spectral characterization of the (E)-3-benzylideneindolin-2-one is reported. The compound crystallized in the monoclinic system with space group P21/n with cell coordinates a= 3.9849 (2) Å, b= 22.2236 (9) Å, c= 12.2501 (5) Å, β= 95.0535 (12) ∘, V=1080.64 (8) Å 3, and Z= 4. In the crystal, molecules are packed in chains formed via weak intermolecular C13–H13A ⋯O1 and N1-H1N1 …O1 hydrogen bonding. The relative stabilities of the two tautomeric isomers of 3 are calculated by DFT/B3LYP method using 6-311G(d,p) basis set in gas phase and in solution. The quantum chemical calculations, NMR studies and the XRD analyses showed that the keto form T0 is the only form that could exist in gas, solution and solid phases respectively. The calculated geometric parameters of the dimer molecule showed better agreement with the XRD data than those obtained for single isolated molecule. This shed light on the effect of intermolecular interactions on the calculated geometric parameters. MEP study showed that, the O-atom and the NH proton are the most reactive H-acceptor and H-donor sites, respectively. The N-H...O H-bonding interactions increased the negative charge at the O-atoms and the positive charge of the NH protons compared to the monomer unit. The synthesis, X-ray single crystal structure, spectral characterizations and DFT computation of the (E)-3-benzylideneindolin-2-one 3 is reported.

Research on Synthesis of New Azo Calix[4]arene and its Dyeing Properties

With the raw materials of calix[4]arene, benzocaine, tricaine and procaine hydrochloride, three new azo calix[4]arene derivatives—6a, 6b and 6c are synthesized by diazotization–coupling reaction of an aromatic amine, with its yield of 83%, 81% and 83% respectively. The structural characterization is in a way of IR, 1H NMR and elemental analysis. This paper investigates the spectral properties of azo calix[4]arene derivatives under different solution pH conditions through the UV–visible spectroscopy, and researches the dyeing properties through the dyeing curve, color yield test and fastness test. The results show that, with the increase of pH value, the azo calix[4]arene derivatives—6a, 6b and 6c form azo–hydrazone tautomeric isomers with the maximum absorption peak redshift; the dyeing effect of the compound is good, of which the dye–uptake rate of the compound 6a is as high as 78%; the surface depth of color yield is 2.798, and the dry and wet rubbing fastness and the soaping fastness are respectively 4, which is a better disperse dye.

Protonation/deprotonation process of Emodin in aqueous solution and pKa determination: UV/Visible spectrophotometric titration and quantum/molecular mechanics calculations

We combined theoretical and experimental studies to elucidate the important deprotonation process of Emodin in water. We used the UV/Visible spectrophotometric titration curves to obtain its pKa values, pKa1=8.0±0.1 and pKa2=10.9±0.2. Additionally, we obtained the pKa values of Emodin in the water–methanol mixture (1:3v/v). We give a new interpretation of the experimental data, obtaining apparent pKa1=6.2±0.1, pKa2=8.3±0.1 and pKa3>12.7.Performing quantum mechanics calculations for all possible deprotonation sites and tautomeric isomers of Emodin in vacuum and in water, we identified the sites of the first and second deprotonation. We calculated the standard deprotonation free energy of Emodin in water and the pKa1, using an explicit model of the solvent, with Free Energy Perturbation theory in Monte Carlo simulations obtaining, ΔGaq=12.1±1.4kcal/mol and pKa1=8.7±0.9. With the polarizable continuum model for the solvent, we obtained ΔGaq=11.6±1.0kcal/mol and pKa1=8.3±0.7. Both solvent models gave theoretical results in very good agreement with the experimental values.

Interplay between hydroxyl radical attack and H-bond stability in guanine–cytosine

We combine ONIOM simulations with an elaborated hydrated DNA model to evaluate the effects of the hydroxyl radical, one of the major products in irradiated cells, on the stability of the guanine–cytosine (G:C) base pair. Our results demonstrate that the addition of the hydroxyl radical to the cytosine moiety results in inter-base hydrogen bonds rearrangements, eventually leading to a so-called rare tautomeric isomer. In these processes, the O6(G)–N4(C) hydrogen bond strength plays a crucial role as one of the driving forces for the double proton transfer. We also demonstrate that the surrounding environment affects the stability of the non-canonical mutagenic forms. As in undamaged DNA, the water molecules of the first hydration shell might catalyze the exchange of protons while π-stacking tunes the energetic profile of the reaction. The degenerative effects of the induced rare tautomers are shown to be governed by the transition states along the PT reactions, which in turn determines their lifetimes.

Synthetic Studies on Novel 1,4-Dihydro-2-methylthio-4,4,6-trisubstituted Pyrimidine-5-carboxylic Acid Esters and Their Tautomers

A mixture of alkyl 1,4-dihydro-2-methylthio-4,4,6-trisubstituted pyrimidine-5-carboxylate 1 and its tautomeric isomer, alkyl 1,6-dihydro-2-methylthio-4,6,6-trisubstituted pyrimidine-5-carboxylate 2 is synthesized by the Atwal-Biginelli cyclocondensation reaction of S-methylisothiourea hemisulfate salt 3 with 2-(gem-disubstituted)methylene-3-oxoesters 4 that can be accessed by the Lehnert procedure for the Knoevenagel-type condensation. The structures of the tautomeric products of the Atwal-Biginelli cyclocondensation reaction, 1 and 2, which are inseparable from each other, are determined unambiguously by (1)H-NMR spectroscopy at various temperatures and nuclear Overhauser enhancement spectroscopy (NOESY) experiment. Because these dihydropyrimidine products are otherwise inaccessible and thus hitherto unavailable, the synthetic methods established in this study will help to expand the molecular diversity of their related derivatives.

Sterically Encumbered Iridium Bis(N-heterocyclic carbene) Systems: Multiple C−H Activation Processes and Isomeric Normal/Abnormal Carbene Complexes

The reaction of [Ir(coe)2Cl]2 (coe = cyclooctene) with the N-heterocyclic carbene N,N′-bis(2,6-diisopropylphenyl)imidazol-2-ylidene (IPr) in tetrahydrofuran under anaerobic conditions leads to the formation of two main products, the planar four-coordinate Ir(I) complex Ir(IPr)(IPr′′)Cl (1) formed by dehydrogenation of one of the IPr isopropyl substituents (to give the mixed NHC/alkene donor IPr′′) and the trigonal bipyramidal Ir(III) system Ir(IPr)(aIPr)(H)2Cl (6), which features both “normal” and “abnormal” C-bound isomers of the NHC ligand. Formation of 1 presumably proceeds via initial C−H activation at iridium(I); moreover, subsequent reactivity for 1 initiated by chloride abstraction suggests that C−H oxidative addition chemistry is facile for the methyl C−H bonds of the carbene isopropyl substituent. Thus, the square pyramidal Ir(III) alkene alkyl hydride [Ir(IPr′)(IPr”)H]+[BArf4]− (2) is formed on reaction with Na[BArf4] in fluorobenzene. In contrast to the Ir(I) system 1, the alignment of the alkene ligand in solid 2 is such that it lies coplanar with the IrC4 basal plane. Quantum chemical investigations imply that the energetic difference between this alkene orientation and an alternative perpendicular conformation is small (ca. 5 kcal mol−1), with steric factors (notably at the alkene 2-position) being important. Hydrogenation of 1 proceeds via an intermediate identified as Ir(IPr)(IPr′′)(H)2Cl to give the Ir(III) dihydride Ir(IPr)2(H)2Cl (4), the structure of which can be compared with those of the tautomeric isomer 6 and the mixed IPr/IMes carbene complex Ir(IPr)(IMes)(H)2Cl [IMes = N,N′-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene]. Crystallographically determined bond lengths for the Ir−C linkages trans to the respective carbenes imply relatively similar σ-donor properties for the IPr, aIPr, and IMes ligands.

Molecular Structure of the trans and cis Isomers of Metal-Free Phthalocyanine Studied by Gas-Phase Electron Diffraction and High-Level Quantum Chemical Calculations: NH Tautomerization and Calculated Vibrational Frequencies

The molecular structure of the trans isomer of metal-free phthalocyanine (H2Pc) is determined using the gas electron diffraction (GED) method and high-level quantum chemical calculations. B3LYP calculations employing the basis sets 6-31G**, 6-311++G**, and cc-pVTZ give two tautomeric isomers for the inner H atoms, a trans isomer having D2h symmetry and a cis isomer having C2v symmetry. The trans isomer is calculated to be 41.6 (B3LYP/6-311++G**, zero-point corrected) and 37.3 kJ/mol (B3LYP/cc-pVTZ, not zero-point corrected) more stable than the cis isomer. However, Hartree-Fock (HF) calculations using different basis sets predict that cis is preferred and that trans does not exist as a stable form of the molecule. The equilibrium composition in the gas phase at 471 degrees C (the temperature of the GED experiment) calculated at the B3LYP/6-311++G** level is 99.8% trans and 0.2% cis. This is in very good agreement with the GED data, which indicate that the mole fraction of the cis isomer is close to zero. The transition states for two mechanisms of the NH tautomerization have been characterized. A concerted mechanism where the two H atoms move simultaneously yields a transition state of D2h symmetry and an energy barrier of 95.8 kJ/mol. A two-step mechanism where a trans isomer is converted to a cis isomer, which is converted into another trans isomer, proceeds via two transition states of C(s) symmetry and an energy barrier of 64.2 kJ/mol according to the B3LYP/6-311++G** calculation. The molecular geometry determined from GED is in very good agreement with the geometry obtained from the quantum chemical calculations. Vibrational frequencies, IR, and Raman intensities have been calculated using B3LYP/6-311++G**. These calculations indicate that the molecule is rather flexible with six vibrational frequencies in the range of 20-84 cm(-1) for the trans isomer. The cis isomer might be detected by infrared matrix spectroscopy since the N-H stretching frequencies are very different for the two isomers.

Synthesis, characterization and crystal structure of the tridentate metalloligand formed from mono-condensation of ferrocenoylacetone and 1,2-phenylenediamine

Reaction of the ferrocenoylacetone 1 with o-phenylenediamine in refluxing dry toluene affords the new air and thermally stable organometallic tridentate compound (“half unit”) 2, which was isolated and characterized by elemental analysis, IR, UV–visible, 1H and 13C NMR spectroscopy and, in addition, authenticated by a single crystal X-ray diffraction analysis. In solution, the metalloligand 2 exists as a mixture of two tautomeric isomers: a keto-amine or enaminone form (60%), CpFe(η 5-C 5H 4)–C(O)CH C(CH 3)N(H)- o-C 6H 4NH 2 (Cp = η 5-C 5H 5), and a keto-imine or iminone form (40%), CpFe(η 5-C 5H 4)–C(O)CH 2C(CH 3)N- o-C 6H 4NH 2, whereas only the enaminone form is found in the solid state. The structure of 2 is stabilized by a network of intra- and intermolecular hydrogen bonds involving N–H, NH 2 and C O groups.

Ultraviolet–visible spectroscopic study of 3,5-dithio-2,7-dimethyl-[1,2,4]-triazepine: Qualitative analysis of tautomeric behaviour

Room temperature UV–vis absorption spectra of the tautomeric system 3,5-dithio-2,7-dimethyl-[1,2,4]-triazepine in solution, in acetonitrile (CH 3CN), are measured at different water volume percentages. The comparison of the obtained measures to the calculated allowed absorption transitions, using ZINDO/S package, reveals the coexistence of all the tautomeric forms in aprotic polar solution with a high dominance of the dithione form. The solute–water hydrogen bond, which seems to be of 1: n-type, favours the dithiol and monothiol conformers to the detriment of the dithione one. Further experimental investigations lead to the result that standing at ambient Laboratory conditions in the dark favours the dithione tautomeric isomer, while standing at indirect sunlight shifts the tautomeric equilibrium away from this specie.

UCS1025A and B, new antitumor antibiotics from the fungus Acremonium species.

[structure: see text] UCS1025A and B, novel pentacyclic polyketides with an unprecedented furopyrrolizidine skeleton, were isolated from the fungus Acremonium sp. KY4917. The structures and stereochemistry were elucidated by a combination of two-dimensional NMR and X-ray crystallographic analysis. UCS1025A showed unique chemical equilibria involving three tautomeric isomers and exhibited antimicrobial activity and antiproliferative activity against human tumor cell lines.