Stereomutations of atropisomers of sterically hindered salophen ligands

[structure: see text] The stereomutations in nonsymmetrical salophen ligands 1-4 were studied by means of dynamic NMR and HPLC methods. DNMR experiments showed that in DMSO-d(6) hindered ligands 2-4 exist in two chiral conformations, depending on whether the imine carbon atoms are in a cis or trans disposition with respect to the plane of the central o-phenylenediamine ring, the latter being more stable by 1.0 kcal mol(-1). Owing to its higher dipole moment, in the apolar solvent C(6)D(6) the cis conformer is destabilized with respect to the trans one, in agreement with the results of ab initio calculations. In DMSO-d(6) solution the two conformers are in equilibrium through the less hindered rotation about the C6-N7 bond aligned to the a(6,7) axis, and the interconversion barriers range from 18.4 to 19.3 kcal mol(-1). The enantiomerization process is a two step-process that implies sequential rotations around the C6-N7 and the C1-N8 bonds, so that the rate determining step is the slower rotation around the more hindered C1-N8 bond aligned to the a(1,8) axis, and the energy barriers range from 21.4 to 21.9 kcal mol(-1). These values compare well with those determined by chromatography on an enantioselective HPLC column at low temperature, thus confirming that DNMR and DHPLC can be conveniently employed as complementary techniques.     

Generation of Reactive Oxygen Species during the Photolysis of 6‐(Hydroxymethyl)pterin in Alkaline Aqueous Solutions

Photochemical studies of the reactivity of 6‐(hydroxymethyl)pterin (=2‐amino‐6‐(hydroxymethyl)pteridin‐4(1H)‐one; HPT) in alkaline aqueous solutions (pH 10.2–10.8) at 350 nm and room temperature were performed. The photochemical reactions were followed by UV/VIS spectrophotometry, thin‐layer chromatography (TLC), high‐performance liquid chromatography (HPLC), and an enzymatic method for H₂O₂ determination. In the presence of O₂, 6‐formylpterin (=2‐amino‐3,4‐dihydro‐4‐oxopteridine‐6‐carboxaldehyde; FPT) was the only photoproduct detected. In the absence of O₂, we observed a compound with an absorbance maximum at 480 nm, which was oxidized very rapidly by O₂ in a dark reaction to yield FPT. The quantum yields of substrates disappearance and of photoproducts formation were determined. The formation of H₂O₂ during photooxidation was monitored, and the number of mol of H₂O₂ released per mol of HPT consumed corresponded to a 1 : 1 stoichiometry. HPT was also investigated for efficiency of singlet‐oxygen (¹O₂) production and quenching in aqueous solution. The quantum yield of ¹O₂ production (Φ_Δ=0.21±0.01) was determined by measurements of the ¹O₂ luminescence in the near‐IR (1270 nm) upon continuous excitation of the sensitizer. The rate constant of ¹O₂ total quenching by HPT was determined (k_t=3.1?10⁶ M ^?1 s^?1), indicating that this compound was able to quench ¹O₂. However, ¹O₂ did not participate in the photooxidation of HPT to FPT.     

SERRS as a more sensitive technique for the detection of labelled oligonucleotides compared to fluorescence

This communication contains data from a comparison between the detection limits obtained using surface enhanced resonance Raman scattering (SERRS) and fluorescence detection of dye labelled oligonucleotides. The results show that the detection limits for SERRS are generally at least three orders of magnitude lower than those obtained for fluorescence.     

Synthesis, chromatographic separation, vibrational circular dichroism spectroscopy, and ab initio DFT studies of chiral thiepane tetraol derivatives

Optically pure enantiomers of the chiral tetrahydroxythiepane derivative 3,6-dihydroxy-4,5-O-isopropylidene-thiepane (3) are obtained using a novel protocol in which a library of all possible stereoisomers of 3 is synthesized, followed by two-step stereoselective chromatography, using, first, conventional achiral and, then, chiral stationary phases. Configurational and conformational analysis of 3 are carried out using Vibrational Circular Dichroism (VCD) spectroscopy in conjunction with ab initio DFT calculations. The absolute configuration of 3 is shown to be 3R,4S,5R,6R-(+)/3S,4R,5S,6S-(-).     

Clustering of nonpolar organic compounds in lipid media: evidence and implications

Semivolatile and nonpolar organic compounds, such as persistent organic pollutants, have a tendency to accumulate in organic matter phases from air and water. Once they enter living systems, they partition into lipids/waxes and can exert adverse toxicological effects. The current paradigm assumes that such chemicals are uniformly distributed in organic phases such as soil organic matter, plant waxes, and animal lipids and that partitioning and adsorption processes occur independently of intermolecular contaminant interactions. With use of a recently developed technique, two-photon excitation microscopy coupled with autofluorescence allowed us to directly visualize novel organic chemical behavior in living vegetation and other matrixes. Here, we show for the first time that polycyclic aromatic hydrocarbons, which were uniformly distributed in pure oils and waxes at the beginning of a study, form clusters over time. The number and diameter (typically 0.2-5 microm) of these clusters are dependent on the physical-chemical properties of the compound-media systems and time. This behavior is not accounted for in current models of phase partitioning of chemicals and may have important implications for understanding their environmental fate and their potential toxicological effects.     

DFT study and NBO analysis of the mutual interconversion of cumulene compounds

The B3LYP/6‐31G* method was used to investigate the configurational properties of allene (1,2‐propadiene) ( 1 ), 1,2,3‐butatriene ( 2 ), 1,2,3,4‐pentateriene ( 3 ), 1,2,3,4,5‐hexapentaene ( 4 ), 1,2,3,4,5,6‐heptahexaene ( 5 ), 1,2,3,4,5,6,7‐octaheptaene ( 6 ), 1,2,3,4,5,6,7,8‐nonaoctaene ( 7 ), and 1,2,3,4,5,6,7,8,9‐decanonaene ( 9 ). The calculations at the B3LYP/6‐31G* level of theory showed that the mutual interconversion energy barrier in compounds 1 – 8 are: 209.73, 131.77, 120.34, 85.00, 80.91, 62.19, 55.56, and 46.83 kJ mol^?1, respectively. The results showed that the difference between the average C?C double bond lengths ( ) values in cumulene compounds 1 and 2 , is larger than those between 7 and 8 , which suggest that with large n (number of carbon atoms in cumulene chain), the values approach a limiting value. Accordingly, based on the plotted data, the extrapolation to n = ∞, gives nearly the same limiting (i. e., ). Also, NBO results revealed that the sum of π‐bond occupancies, , decrease from 1 to 8 , and inversely, the sum of π‐antibonding orbital occupancies, , increase from compound 1 to compound 8 . The decrease of values for compounds 1 – 8 , is found to follow the same trend as the barrier heights of mutual interconversion in compounds 1 – 8 , while the decrease of the barrier height of mutual interconversion in compounds 1 – 8 is found to follow the opposite trend as the increase in the number of carbon atom. Accordingly, besides the previously reported allylic resonant stabilization effect in the transition state structures, the results reveal that the values, , Δ(E_HOMO ? E_LUMO), and the C atom number could be considered as significant criteria for the mutual interconversion in cumulene compounds 1 – 8 . This work reports also useful predictive linear relationships between mutual interconversion energy barriers ( ) in cumulene compounds and the following four parameters: , , Δ(E_HOMO ? E_LUMO), and C_Number. Copyright © 2007 John Wiley & Sons, Ltd.     

Reduction of variables for Willmore-Chen submanifolds in seven spheres

We obtain a reduction of variables criterion for 4-dimensional Willmore-Chen submanifolds associated with the generalized Kaluza-Klein conformal structures on the 7-sphere. This argument connects the variational problem of Willmore-Chen with a variational problem for closed curves into 4-spheres. It involves an elastic energy functional with potential. The method is based on the extrinsic conformal invariance of the Willmore-Chen variational problem, and the principle of symmetric criticality. It also uses several techniques from the theory of pseudo-Riemannian submersions. Furthermore, we give some applications, in particular, a result of existence for constant mean curvature Willmore-Chen submanifolds which is essentially supported on the nice geometry of closed helices in the standard 3-sphere. Partially supported by a DGICYT Grant No. PB97-0784.     

Photochemical Behavior of Folic Acid in Alkaline Aqueous Solutions and Evolution of Its Photoproducts

The photolysis of folic acid (=N‐(4‐{[(2‐amino‐1,4‐dihydro‐4‐oxopteridin‐6‐yl)methyl]amino}benzoyl)‐L ‐glutamic acid) in alkaline aqueous solution (pH 10.0–11.0) was carried out at 350 nm at room temperature and monitored by UV/VIS spectrophotometry, anal. and prep. thin‐layer chromatography (TLC), and high‐performance liquid chromatography (HPLC, HPLC/MS). The folate species underwent at least two independent photo‐oxidation pathways, which were not observed when the acid form was photolyzed at pH<7. The presence of O₂ was essential in these oxidation pathways. Evidence for the role of singlet oxygen was established. In one of the pathways, the folate underwent cleavage, yielding 6‐formylpterin (=2‐amino‐1,4‐dihydro‐4‐oxopteridine‐6‐carboxaldehyde) and (4‐aminobenzoyl)glutamic acid as photoproducts. The other pathway yielded a new photostable product A of molecular mass 455, which could be isolated and stored in acidic or neutral aqueous solution. However, A was rather unstable in alkaline media undergoing a thermal reaction to a product B of lower molecular mass (427). The kinetics of this thermal reaction was analyzed with a stopped‐flow spectrophotometer. A linear dependence of the first‐order rate constant with the OH⁻ concentration was observed. The corresponding bimolecular rate constant was 1.1 M ⁻¹ s⁻¹. The quantum yields of substrate consumption and of photoproduct formation were determined. The here‐reported photochemical behavior of folate solutions departs from results in acid media, where phototransformation proceeded via the cleavage of the acid form into 6‐formylpterin and (4‐aminobenzoyl)glutamic acid as the first major photoproducts, and where no thermal reactions were observed.     

D936Y and Other Mutations in the Fusion Core of the SARS-CoV-2 Spike Protein Heptad Repeat 1: Frequency,Geographical Distribution,and Structural Effect

The crown of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is constituted by its spike (S) glycoprotein. S protein mediates the SARS-CoV-2 entry into the host cells. The “fusion core” of the heptad repeat 1 (HR1) on S plays a crucial role in the virus infectivity, as it is part of a key membrane fusion architecture. While SARS-CoV-2 was becoming a global threat, scientists have been accumulating data on the virus at an impressive pace, both in terms of genomic sequences and of three-dimensional structures. On 15 February 2021, from the SARS-CoV-2 genomic sequences in the GISAID resource, we collected 415,673 complete S protein sequences and identified all the mutations occurring in the HR1 fusion core. This is a 21-residue segment, which, in the post-fusion conformation of the protein, gives many strong interactions with the heptad repeat 2, bringing viral and cellular membranes in proximity for fusion. We investigated the frequency and structural effect of novel mutations accumulated over time in such a crucial region for the virus infectivity. Three mutations were quite frequent, occurring in over 0.1% of the total sequences. These were S929T, D936Y, and S949F, all in the N-terminal half of the HR1 fusion core segment and particularly spread in Europe and USA. The most frequent of them, D936Y, was present in 17% of sequences from Finland and 12% of sequences from Sweden. In the post-fusion conformation of the unmutated S protein, D936 is involved in an inter-monomer salt bridge with R1185. We investigated the effect of the D936Y mutation on the pre-fusion and post-fusion state of the protein by using molecular dynamics, showing how it especially affects the latter one.