Acetyl Carbonyl Research Articles

Structural and antimicrobial properties of 3-[-2-(1,5-dimethy 3-oxo-2-phenyl-2,3- dihydro-1H-pyrazol-4-yl) hydrazilidine]-1,3-diphenylpropane-1,3-dione and its Co(II), Fe(III), Cu(II) and Ni(II) complexes

This work aims at synthesizing new hydrazone molecules with enhanced antibacterial capabilities. Diazotized 4-aminoantipyrine and 1,3-diphenyl-1,3-dione were coupled at around 5 oC to yield 3-[-2-(I,5-dimethy-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl) hydrazilidine]1,3-dione-1,3-diphenylpropane (HPDP). Its Co(II), Fe(III), Cu(II), and Ni(II) complexes were formed by refluxing stoichiometric amounts of chloride salts in separately with HPDP for 6 hours at 60 oC. HPDP and its complexes were characterized by means of spectroscopic techniques, conductivity, micro elemental analysis and melting point. Only HPDP X-ray diffraction spectral was obtained. The in-vitro antibacterial tests of compounds were done on Bacillus subtilis, Streptococcus pneumoniae, Pseudomonas aeruginosa, Escherichia coli (Eco 6 and Eco 13), Staphylococcus aureus, Protus, Staphylococcus intermedius (G101), Klebsiella pneumoniae and Salmonella Typhi. Spectroscopic studies show that HPDP is terdentately coordinated to the metal ion to form octahedral complexes with the acetyl, hydrazinyl nitrogen, and pyrazolone ring carbonyl groups. HPDP crystallized as monochronic with space group PbCa and unit dimensions a = 9.5528(8) Å, α = 90o; b = 19.6260(16) Å, b = 101.426(6)o; c = 12.058(10) Å, g = 90o for z = 4. Antimicrobial evaluations show that HPDP and [Ni(PDP)2] exhibited antibacterial activity against Salmonella. Typhi and Staphylococcus aureus up to the least concentration (0.31 μg/cm3), suggesting their potential for application as antibacterial drugs. KEY WORDS: Selenium, Amino acids, Vitamin B3, Mixed ligand, Complexes, Antioxidant Bull. Chem. Soc. Ethiop. 2024, 38(6), 1691-1702. DOI: https://dx.doi.org/10.4314/bcse.v38i6.15

X-ray structure of the Rhodobacter sphaeroides reaction center with an M197 Phe→His substitution clarifies the properties of the mutant complex.

The first steps of the global process of photosynthesis take place in specialized membrane pigment-protein complexes called photosynthetic reaction centers (RCs). The RC of the photosynthetic purple bacterium Rhodobacter sphaeroides, a relatively simple analog of the more complexly organized photosystem II in plants, algae and cyanobacteria, serves as a convenient model for studying pigment-protein interactions that affect photochemical processes. In bacterial RCs the bacteriochlorophyll (BChl) dimer P serves as the primary electron donor, and its redox potential is a critical factor in the efficient functioning of the RC. It has previously been shown that the replacement of Phe M197 by His strongly affects the oxidation potential of P (E m P/P+), increasing its value by 125 mV, as well as increasing the thermal stability of RC and its stability in response to external pressure. The crystal structures of F(M197)H RC at high resolution obtained using various techniques presented in this report clarify the optical and electrochemical properties of the primary electron donor and the increased resistance of the mutant complex to denaturation. The electron-density maps are consistent with the donation of a hydrogen bond from the imidazole group of His M197 to the C2-acetyl carbonyl group of BChl PB. The formation of this hydrogen bond leads to a considerable out-of-plane rotation of the acetyl carbonyl group and results in a 1.2 Å shift of the O atom of this group relative to the wild-type structure. Besides, the distance between BChl PA and PB in the area of pyrrole ring I was found to be increased by up to 0.17 Å. These structural changes are discussed in association with the spectral properties of BChl dimer P. The electron-density maps strongly suggest that the imidazole group of His M197 accepts another hydrogen bond from the nearest water molecule, which in turn appears to form two more hydrogen bonds to Asn M195 and Asp L155. As a result of the F(M197)H mutation, BChl PB finds itself connected to the extensive hydrogen-bonding network that pre-existed in wild-type RC. Dissimilarities in the two hydrogen-bonding networks near the M197 and L168 sites may account for the different changes of the E m P/P+ in F(M197)H and H(L168)F RCs. The involvement of His M197 in the hydrogen-bonding network also appears to be related to stabilization of the F(M197)H RC structure. Analysis of the experimental data presented here and of the data available in the literature points to the fact that the hydrogen-bonding networks in the vicinity of BChl dimer P may play an important role in fine-tuning the redox properties of the primary electron donor.

Molecular Docking, Synthesis, and Tyrosinase Inhibition Activity of Acetophenone Amide: Potential Inhibitor of Melanogenesis.

Tyrosinase and its related proteins are responsible for pigmentation disorders, and inhibiting tyrosinase is an established strategy to treat hyperpigmentation. The carbonyl scaffolds can be effective inhibitors of tyrosinase activity, and the fact that both benzoic and cinnamic acids are safe natural substances with such a scaffolded structure, it was speculated that hydroxyl-substituted benzoic and cinnamic acid derivatives may exhibit potent tyrosinase inhibitory activity. These moieties were incorporated into new chemotypes that displayed in vitro inhibitory effect against mushroom tyrosinase with a view to explore antimelanogenic ingredients. The most active compound, 2-((3-acetylphenyl)amino)-2-oxoethyl(E)-3-(2,4-dihydroxyphenyl)acrylate (5c), inhibited mushroom tyrosinase with an IC50 of 0.0020 ± 0.0002 μM, while 2-((3-acetylphenyl)amino)-2-oxoethyl 2,4-dihydroxybenzoate (3c) had an IC50 of 27.35 ± 3.6 μM in comparison to the positive control arbutin and kojic acid with a tyrosinase inhibitory activity of IC50 of 191.17 ± 5.5 μM and IC50 of 16.69 ± 2.8 μM, respectively. Analysis of enzyme kinetics revealed that 5c is a competitive and reversible inhibitor with dissociation constant (Ki) value 0.0072 μM. In silico docking studies with mushroom tyrosinase (PDB ID 2Y9X) predicted possible binding modes in the enzymatic pocket for these compounds. The orthohydroxyl of the cinnamic acid moiety of 5c is predicted to form hydrogen bond with the active site side chain carbonyl of Asn 260 (2.16 Å) closer to the catalytic site Cu ions. The acetyl carbonyl is picking up another hydrogen bond with Asn 81 (1.90 Å). The inhibitor 5c passed the panassay interference (PAINS) alerts. This study presents the potential of hydroxyl-substituted benzoic and cinnamic acids and could be beneficial for various cosmetic formulations.

Real‐Time Interrogation of Aspirin Reactivity, Biochemistry, and Biodistribution by Hyperpolarized Magnetic Resonance Spectroscopy

AbstractHyperpolarized magnetic resonance spectroscopy enables quantitative, non‐radioactive, real‐time measurement of imaging probe biodistribution and metabolism in vivo. Here, we investigate and report on the development and characterization of hyperpolarized acetylsalicylic acid (aspirin) and its use as a nuclear magnetic resonance (NMR) probe. Aspirin derivatives were synthesized with single‐ and double‐13C labels and hyperpolarized by dynamic nuclear polarization with 4.7 % and 3 % polarization, respectively. The longitudinal relaxation constants (T1) for the labeled acetyl and carboxyl carbonyls were approximately 30 seconds, supporting in vivo imaging and spectroscopy applications. In vitro hydrolysis, transacetylation, and albumin binding of hyperpolarized aspirin were readily monitored in real time by 13C‐NMR spectroscopy. Hyperpolarized, double‐labeled aspirin was well tolerated in mice and could be observed by both 13C‐MR imaging and 13C‐NMR spectroscopy in vivo.

Inversion of Optical Activity in the Synthesis of Mercury Sulfide Nanoparticles: Role of Ligand Coordination

AbstractOptical activity in inorganic colloidal materials was controlled through interactions of chiral molecules with the nanoparticle (NP) surface. An inversion of optical activity in the synthesis of mercury sulfide (HgS) NPs was demonstrated with an intrinsically chiral crystalline system in the presence of an identical chiral capping ligand. A continuous decrease in the positive first Cotton effect and an eventual reversal of CD profile were observed upon heating the aqueous solution of HgS NPs capped with N‐acetyl‐l‐cysteine (Ac‐l‐Cys) at 80 °C. Ac‐l‐Cys afforded two bidentate coordination configurations with an almost mirror image of each other using the thiolate and either of carboxylate or acetyl–carbonyl groups on the HgS core. Experiment and calculation suggest that a shift in the distribution of the NP formation with energy in response to the combinations of ligand coordination structure and chiral crystalline surface is responsible for the inversion of optical activity.

New voltammetric method useful for water insoluble or weakly soluble compounds: application to pKa determination of hydroxyl coumarin derivatives

Here, we reveal a different way of doing the voltammetric experiments that considers the electroactive species packaged in the electrodic phase instead of dissolved in solution. In this way, it is possible to obtain voltammograms of insoluble species. In this work, the method is exemplified by obtaining voltammograms for weakly soluble coumarins but it could be extrapolated to other weakly soluble compounds. We have studied a comprehensive series of 3-acetyl-hydroxycoumarins derivatives which are insoluble in aqueous medium but capable of being trapped in a three-dimensional multi-walled carbon nanotubes (MWCNT) network. Consequently, an electrodic phase composed of an MWCNT modified glassy carbon electrode (GCE) containing the coumarin derivative is prepared. The voltammetric experiment is performed with the above electrodic phase and an aqueous medium as the solution phase. All the coumarin derivatives show one anodic peak due to the oxidation of the hydroxyl group in the phenyl ring. The oxidation peaks follow a one-electron, one-proton irreversible, pH-dependent process for all monohydroxylated compounds. The Ep values are closely dependent of the substituent effect being the 7,8-cum derivative more easily oxidized due to both the electron donor effect of neighboring hydroxyls groups and hydrogen bonding interaction between them. On the other hand, the hydroxyl of the 7-cum derivative is the most difficult to oxidize due to the electron-attracting effect of the lactone carbonyl group at position 2 and acetyl carbonyl at position 3 which is conjugated with OH at 7 positions. From the breaks in the graphs Ep versus pH, we estimate the voltammetric pKa values for all the studied coumarin derivatives.

Trans-Acetyldicarbonyl(η5-cyclopentadienyl)[tris(3,5-dimethylphenyl)phosphane-κP]molybdenum(II)

The title compound, [Mo(C5H5)(C2H3O)(C24H27P)(CO)2], was prepared by reaction of [Mo(C5H5)(CO)3(CH3)] with tris(3,5-dimethylphenyl)phosphane. The complex exhibits a four-legged piano-stool geometry with trans-disposed acetyl and phosphane ligands. The molecular geometry is nearly identical to that of the triphenylphosphane derivative, but introduction of methyl groups on the aromatic phosphane substituents significantly impacts supramolecular organization. In the crystal, non-classical C—H...O interactions involving the acetyl carbonyl group lead to a chain motif along [010], and another set of C—H...O close contacts join inversion-related molecules.

Chemistry of 2,5-dihydroxyacetophenone, a Key Chromophore in Cellulosic Substrates

2,5-Dihydroxyacetophenone (DHAP) is one of the three key chromophores found in aged cellulosics. Knowledge of the general reactivity and chemistry of this compound is helpful for a better understanding of cellulose aging and yellowing as well as bleaching of cellulosic materials - processes that also have considerable economic importance. This paper reviews the reactions reported for 2,5- dihydroxyacetophenone from the viewpoints of both synthesis and general reactivity. The compound exhibits a rich chemistry due to the superposition of the hydroquinone structure and the 2-hydroxyacetophenone structure with its α-hydroxy ortho-quinone methide tautomer. The 1-acetyl group exhibits high reactivity attributed to resonance of the carbonyl group with the π-electrons of the benzene ring and proton donation to the carbonyl group from the adjacent 2-hydroxy group. One of the prominent conversion paths for DHAP are aldol-type reactions that have been applied for the synthesis of a multitude of flavonoids. Other reaction pathways are nucleophilic substitution on the carbonyl group mainly with amines, electrophilic addition to the benzene ring, and oxidation into the corresponding benzoquinone. There are also quite a few reports of selective derivatization of the 5-hydroxy group of DHAP that has a higher reactivity than its 2-OH counterpart that is engaged in tight hydrogen bonding with the acetyl carbonyl moiety and thus largely blocked in esterifications and similar derivatizations. Keywords: 2-hydroxy-acetophenones, aging, aldol reaction, bleaching, cellulose, chromophore, reaction mechanism.

Structure, morphology and functionality of acetylated and oxidised barley starches

Acetylation and oxidation are chemical modifications which alter the properties of starch. The degree of modification of acetylated and oxidized starches is dependent on the catalyst and active chlorine concentrations, respectively. The objective of this study was to evaluate the effect of acetylation and oxidation on the structural, morphological, physical–chemical, thermal and pasting properties of barley starch. Barley starches were acetylated at different catalyst levels (11%, 17%, and 23% of NaOH solution) and oxidized at different sodium hypochlorite concentrations (1.0%, 1.5%, and 2.0% of active chlorine). Fourier-transformed infrared spectroscopy (FTIR), X-ray diffractograms, thermal, morphological, and pasting properties, swelling power and solubility of starches were evaluated. The degree of substitution (DS) of the acetylated starches increased with the rise in catalyst concentration. The percentage of carbonyl (CO) and carboxyl (COOH) groups in oxidized starches also increased with the rise of active chlorine level. The presence of hydrophobic acetyl groups, carbonyl and carboxyl groups caused a partial disorganization and depolymerization of starch granules. The structural, morphological and functional changes in acetylated and oxidized starches varied according to reaction conditions. Acetylation makes barley starch more hydrophobic by the insertion of acetyl groups. Also the oxidation promotes low retrogradation and viscosity. All these characteristics are important for biodegradable film production.

Significant Substituent Effect on the Anomerization of Pyranosides: Mechanism of Anomerization and Synthesis of a 1,2‐cis Glucosamine Oligomer from the 1,2‐trans Anomer

Aminoglycosides containing a 2,3-trans carbamate group easily undergo anomerization from the 1,2-trans glycoside to the 1,2-cis isomer under mild acidic conditions. The N-substituent of the carbamate has a significant effect on the anomerization reaction; in particular, an N-acetyl group facilitated rapid and complete α-anomerization. The differences in reactivity due to the various N-substituents were supported by the results of DFT calculations; the orientation of the acetyl carbonyl group close to the anomeric position was found to contribute significantly to the directing of the anomerization reaction. By exploiting this reaction, oligoaminoglycosides with multiple 1,2-cis glycosidic bonds were generated from 1,2-trans glycosides in a one-step process.

Ligand Effects on Reactivity of Cobalt Acyl Complexes

Hydrogenolysis reactions of cobalt acyl complexes, [Co(CO)3(L)(COR)] (L = phosphine, R = Me, nPr) have been monitored using in situ IR spectroscopy at moderate temperatures (<75 °C) and pressures (<25 bar). The reactions provide a model for the product-formation step in phosphine-modified, cobalt-catalyzed hydroformylation. The reaction kinetics are dependent on L, with the fastest rate being observed for the complex containing n-pentyl-9-phosphabicyclo[4.2.1]nonane (a5-PhobPC5). The observed dependence of rate on H2 and CO pressure is consistent with a mechanism involving initial CO dissociation, followed by reaction of [Co(CO)2(L)(COR)] with H2. Isotopic exchange experiments, monitored by IR spectroscopy, demonstrate that both terminal and acetyl carbonyls of [Co(CO)3(L)(COR)] exchange with free 13CO. Kinetic data are also reported for reactions of [Co(CO)3(L)(COR)] with triphenyltinhydride. A zero-order dependence on [Ph3SnH] (at large excess) and positive values of ΔS‡ demonstrate rate-determining CO dissociation. For a series of less bulky, symmetrical phosphines, the rates follow the sequence PEt3 < PMe2Ph ∼ PEtPh2 < PPh3 < P(4-ClC6H4)3, in accord with their electron-donating strength. Higher rates are found for more bulky phosphines, and the fastest rate is again found for L = a5-PhobPC5. Calculations using density functional theory indicate that the CO dissociation energy for [Co(CO)3(L)(COMe)] is influenced by the stereoelectronic properties of L, with steric bulk having a substantial effect. X-ray crystal structures are reported for [Co(CO)3(PEtPh2)(COMe)], [Co(CO)3(s-PhobPC5)]2, and [Co(CO)3(a5-PhobPC5)]2.

Cavity Closure Dynamics of Peracetylated β-Cyclodextrins in Supercritical Carbon Dioxide

Structural properties of peracetylated β-cyclodextrin in supercritical carbon dioxide were investigated by means of molecular dynamics simulations. The study indicated a strong reduction of the cavity accessibility to guest molecules, compared to native β-cyclodextrin in water. Indeed, the cavity is self-closed during the largest part of the simulation, which agrees well with suggestions made on the basis on high-pressure NMR experiments. Self-closure happens because one glucose unit undergoes a main conformational change (from chair to skew) that brings one of the acetyl groups in the wide rim of the cyclodextrin to the cavity interior. This arrangement turns out to be quite favorable, persisting for several nanoseconds. In addition to the wide rim self-closure, a narrow rim self-closure may also occur, though it is less likely and exhibits short duration (<1 ns). Therefore, the number of solvent molecules reaching the cavity interior is much smaller than that found in the case of native β-cyclodextrin in water after correction to account for different molar densities. These findings support the weak tendency of the macromolecule to form host-guest complexes in this nonconventional medium, as reported by some experiments. Finally, Lewis acid/base interactions between the acetyl carbonyl groups and the solvent CO(2) molecules were analyzed through ab initio calculations that revealed the existence of a quite favorable four-member ring structure not yet reported. The ensemble of these results can contribute to establish general thermodynamic principles controlling the formation of inclusion complexes in supercritical CO(2), where the hydrophilicity/hydrophobicity balance is not applicable.

Molecular dynamics simulation of the dissolution process of a cellulose triacetate-II nano-sized crystal in DMSO

An understanding of the dissolution process of cellulose derivatives is important not only for basic research but also for industrial purposes. We investigated the dissolution process of cellulose triacetate II (CTA II) nano-sized crystal in DMSO solvent using molecular dynamics simulations. The nano-sized crystal consists of 18 CTA chains. During the 9 ns simulation, it was observed that one chain (C01) located at the corner of the lozenge crystal was solvated by the DMSO molecules and moved away from the remaining cluster into the DMSO solvent. The analysis showed that the breakage of the interaction between the H1, H3, and H5 hydrogens of the pyranose ring and the acetyl carbonyl oxygen in the C01 and C02 adjacent chains would be crucial for the dissolution of CTA. The DMSO molecules solvating around these atoms would prevent the re-crystallization of the CTA molecules and facilitate further dissolution.

Structure and reaction pathways of methyl lactate on Pd(1 1 1)

The adsorption and reaction of methyl lactate (CH 3CH(OH)COOCH 3) is studied in ultrahigh vacuum on a Pd(1 1 1) surface using temperature-programmed desorption (TPD) and reflection–absorption infrared spectroscopy (RAIRS). Methyl lactate reacts at relatively low temperatures (∼220 K) by O–H bond scission. This intermediate can either react with hydrogen to reform methyl lactate at ∼280–300 K or undergo β-hydride elimination to form flat-lying methyl pyruvate. This decomposes to form acetyl and methoxy carbonyl species as found previously following methyl pyruvate adsorption on Pd(1 1 1). These species predominantly react to form carbon monoxide, methane and hydrogen.

Binding Modes of Aromatic Ligands to Mammalian Heme Peroxidases with Associated Functional Implications: CRYSTAL STRUCTURES OF LACTOPEROXIDASE COMPLEXES WITH ACETYLSALICYLIC ACID, SALICYLHYDROXAMIC ACID, AND BENZYLHYDROXAMIC ACID

The binding and structural studies of bovine lactoperoxidase with three aromatic ligands, acetylsalicylic acid (ASA), salicylhydoxamic acid (SHA), and benzylhydroxamic acid (BHA) show that all the three compounds bind to lactoperoxidase at the substrate binding site on the distal heme side. The binding of ASA occurs without perturbing the position of conserved heme water molecule W-1, whereas both SHA and BHA displace it by the hydroxyl group of their hydroxamic acid moieties. The acetyl group carbonyl oxygen atom of ASA forms a hydrogen bond with W-1, which in turn makes three other hydrogen-bonds, one each with heme iron, His-109 N(epsilon2), and Gln-105 N(epsilon2). In contrast, in the complexes of SHA and BHA, the OH group of hydroxamic acid moiety in both complexes interacts with heme iron directly with Fe-OH distances of 3.0 and 3.2A respectively. The OH is also hydrogen bonded to His-109 N(epsilon2) and Gln-105N(epsilon2). The plane of benzene ring of ASA is inclined at 70.7 degrees from the plane of heme moiety, whereas the aromatic planes of SHA and BHA are nearly parallel to the heme plane with inclinations of 15.7 and 6.2 degrees , respectively. The mode of ASA binding provides the information about the mechanism of action of aromatic substrates, whereas the binding characteristics of SHA and BHA indicate the mode of inhibitor binding.

Steric structure of alkyl 2-aryl(hetaryl)hydrazono-3-fluoroalkyl-3-oxopropionates

Steric structure of fluorinated 2-arylhydrazono-3-oxo esters was studied by 1H, 19F, and 13C NMR spectroscopy and X-ray analysis. It was found that these compounds in the crystalline state and in solutions in acetone-d6, DMSO-d6, and CDCl3 exist as Z isomers with the ester fragment involved in intramolecular hydrogen bond with the hydrazone NH proton. Exceptions are alkyl 2-arylhydrazono-4,4-difluoro-3-oxobutanoates which exist in acetone-d6 as mixtures of Z and E isomers, the former prevailing. Unlike fluorinated analogs, ethyl 2-(4-methylphenyl)hydrazono-3-oxobutanoate in crystal has the structure of E isomer in which intramolecular hydrogen bond is formed between the NH proton and acetyl carbonyl group. The same compound in acetone-d6, DMSO-d6, and CDCl3 gives rise to a mixture of Z and E isomers, the latter prevailing.

1-naphthylazo derivatives of some 1,3-dicarbonyl compounds and their Cu (II), Ni(II) and Zn(II) complexes

The coupling of diazotized 1-aminonaphthalene with 1,3-dicarbonyl compounds (acetylacetone, methylacetoacetate and acetoacetanilide) yielded a new series of bidentate ligand systems (HL). Analytical, IR, 1H-NMR and mass spectral data indicate that the compounds exist in the intramolecularly hydrogen bonded keto-hydrazone form. With Ni(II), Cu(II) and Zn(II), these potential monobasic bidentate ligands formed [ML2] type complexes. The IR, 1H- -NMR and mass spectral data of the complexes are consistent with the replacement of the chelated hydrazone proton of the ligand by a metal ion, thus leading to a stable six-membered chelate ring involving the hydrazone nitrogen and the hydrogen bonded carbonyl oxygen. The Ni(II) and Zn(II) chelates are diamagnetic, while the Cu(II) complexes are paramagnetic. In the metal complexes of the naphthylazo derivatives of acetylacetone and methylacetoacetate, the acetyl carbonyl is involved in coordination, whereas in the chelates of the naphthylazo derivative of acetoacetanilide, the anilide carbonyl is bonded with the metal ion.

A 310‐helical pentapeptide in water: Interplay of α,α‐disubstituted amino acids and the central residue on structure formation

C(alpha,alpha)-disubstituted amino acids (alphaalphaAAs) are widely used to conformationally constrain peptides. A series of pentapeptides containing dipropylglycine (Dpg) at alternating positions and their alpha-amino acid counterpart L-norvaline (Nva) analogues were synthesized to fully investigate the impact of Dpg on peptide backbone structure in aqueous solution. CD, VCD, and NMR spectral analysis suggest that Dpg containing peptides adopt more ordered structures relative to their Nva containing analogues. The central residues (Ala, Thr, Tyr, Val) and the charged side-chains of Glu and Lys play important roles in the degree of peptide folding. Hydrophobic and branched residues (Val, Tyr) at the central position of the peptide produce greater folding as judged by CD and NMR. Variation of the chemical shift with temperature (Deltadelta/DeltaT NH) of Ac-Glu-Dpg-Tyr-Dpg-Lys-NH(2) suggests a series of i --> i + 3 hydrogen bonds between the N-terminal acetyl carbonyl and the Tyr(3) NH, and the Glu(1) carbonyl and the Dpg(4) NH. The solution conformation of Ac-Glu-Dpg-Tyr-Dpg-Lys-NH(2) calculated from NMR-derived constraints shows a 3(10)-helical structure (two repetitive type-III beta-turns) at residues 1-4, which is supported by 2D NMR, CD, and VCD spectra. Analysis of NMR-derived models of these peptides suggest that there is a strong hydrophobic interaction of the pro-S propyl side chain of Dpg(2) and the Tyr(3) side-chain that may be a strong stabilizing force of the peptide folding in water.

Probing the Lower Size Limit for Protein-Like Fold Stability: Ten-Residue Microproteins With Specific, Rigid Structures in Water

Mutational optimization of two long-range interactions first observed in Ac-WINGKWT-NH2, (a) bifurcated H-bonding involving the threonine amide H(N) and side chain OH and the N-terminal acetyl carbonyl and (b) an H-bond between the entgegen-H(N) of the C-terminal amide and the indole ring of Trp6 that stabilizes a face-to-edge indole/indole interaction between Trp1 and Trp6, has afforded < or = 10 residue systems that yield a remarkably stable fold in water. Optimization was achieved by designing a hydrophobic cluster that sequesters these H-bonds from solvent exposure. The structures and extent of amide H/D exchange protection for CH3CH2CO-WI pGXWTGPS (p = D-Pro, X = Leu or Ile) were determined. These two systems are greater than 94% folded at 298 K (97.5% at 280 K) with melting temperatures > 75 degrees C. The fold appears to display minimal fluxionality; a well-converged NMR structure rationalizes all of the large structuring shifts observed, and we suggest that these designed constructs can be viewed as microproteins.

Direct Observation of Aminyl Radical Intermediate during Single-Crystal to Single-Crystal Photoinduced Orton Rearrangement

A photoinduced analogue of the thermal Orton rearrangement reaction by which an N-chlorine atom from a side amino group is transferred to a phenyl ring was studied in the solid state. Contrary to the mixture of products obtained in solution, in the N-chloro-N-acetylaminobenzene crystals the photoreaction proceeds with complete preservation of crystallinity, affording selectively and quantitatively the para isomer of chloroacetanilide. Study of the reaction mechanism by in situ steady-state photodiffraction, a combination of photoexcitation by UV light and single-crystal X-ray diffraction analysis, provided evidence for creation of N-acetyl-N-phenylaminyl (AcPhN*) radical as a metastable reaction intermediate. The structure of the aminyl radical produced in 9.2% yield from the major disordered component in the statically 85.6:14.4 disordered crystal was directly observed for the first time. The unprecedented stability of the radical is prescribed to the solid-state cage effect, the reactive center of the radical species being locked away from the reactive target molecules. The creation of the radical and its head-to-tail chain reaction within the undulated hydrogen-bonded ribbons involving the acetyl carbonyl group are employed to explain the high selectivity of the photoinduced single-crystal to single-crystal Orton rearrangement. On the basis of the change of the crystal structure and the physicochemical data, a three-center five-atom mechanism involving homolytic cleavage of the N-Cl bond followed by hydrogen abstraction by the carbonyl group is suggested for the solid-state photoinduced Orton rearrangement.