Novel human lens metabolites from normal and cataractous human lenses

4-(2-Aminophenyl)-4-oxobutanoic acid, 4-(2-amino-3-hydroxyphenyl)-4-oxobutanoic acid and glutathionyl-kynurenine have been identified as novel metabolites in normal and cataractous human lenses following total synthesis and comparison with authentic human lens samples. Their structures are consistent with those derived from the major human lens UV filters kynurenine and 3-hydroxykynurenine, and it is proposed that these compounds also play a role as UV filters. These metabolites were isolated in pmol/mg levels (dry mass) in lenses. 4-(2-Amino-3-hydroxyphenyl)-4-oxobutanoic acid and glutathionyl-kynurenine were found to be unstable at physiological pH. Other potential metabolites, glutathionyl-3-hydroxykynurenine, kynurenine yellow and 3-hydroxykynurenine yellow, were not detected in either normal or cataractous lenses.     

Oxygen capture by lithiated organozinc reagents containing aromatic 2-pyridylamide ligands

The sequential reaction of ZnMe2 with a 2-pyridylamine (HN(2-C5H4N)R, R = Ph: 1; 3,5-Xy (=3,5-xylyl): 2; 2,6-Xy: 3; Bz (=benzyl): 4; Me: 5), tBuLi and thereafter with oxygen affords various lithium zincate species, the solid-state structures of which reveal a diversity of oxo-capture modes. Amine 1 reacts to give both dimeric THF [Li(Me)OZn[N(2-C5H4N)Ph]2] (6), wherein oxygen has inserted into the Zn-C bond of a [MeZn[N(2-C5H4N)-Ph]2] ion, and the trigonal Li2Zn complex, bis(OtBu)-capped (THF x Li)2-[[(mu3-O)tBu]2Zn[N(2-C5H4N)Ph]2] (7). The structural analogue of 6 (8) results from the employment of 2, while the use of more sterically congested 3 yields a pseudo-cubane dimer [(THF x [Li(tBu)OZn(OtBu)Me]]2] (9) notable for the retention of labile Zn-C(Me). Amines 4 and 5 afford the oxo-encapsulation products [mu4-O)Zn4[(2-C5H4N)-NBz]6] (10b), and [tBu(mu3-O)-Li3(mu6-O)Zn3[(2-C5H4N)NMe]6] (11), respectively, with concomitant oxo-insertion into a Li-C interaction resulting in capping of the fac-isomeric (mu6-O)M3M'3 distorted octahedral core of the latter complex by a tert-butoxide group.     

Dialysis-Chelex method for determination of exchangeable copper in human plasma

A method based on dialysis in the presence of histidine, and subsequent copper adsorption and preconcentration using Chelex-100 resin, has been developed for selective extraction of exchangeable copper from blood plasma. The method was verified by comparative analysis using two different instrumental techniques, ICP–MS and AAS. The results obtained were in excellent agreement. Accurate quantification of the exchangeable copper and the firmly bound copper was achieved. The method was further validated by analysis of a lyophilised human serum certified reference material.     

Non-unitary scattering and capture. I. Hilbert space theory

By carrying out a general analysis of properties of the wave operators for the non-unitary scattering theory which arises in connection with the use of complex optical potentials in nuclear scattering and elsewhere, we clarify some puzzling differences between two recent approaches to this subject.     

A precise PKPβ+ measurement at Z = 55: (I). The mass of 130Cs

The Q-value for the ¹²⁹Xe(³He, d)¹³⁰Cs reaction is measured to be +5 ± 20 keV. By combining this result with the known neutron separation energy of ¹³⁰Xe, we derive the total decay energy of ¹³⁰Cs

¹³⁰Xe to beQ_EC = 2974 ± 20 keV. This value agrees well with two previous positron end-point measurements but disagrees with the corresponding value derived from the 1977 atomic mass evaluation. This has significance in testing the accuracy of the calculated ratio for ¹³⁰Cs decay. The mass excess of ¹³⁰Cs is derived to be ?86908 ± 14 keV. An excited state in ¹³⁰Cs. was also identified at 121 ± 15 keV with J < 3 and positive parity. The Q-value for ¹³⁶Xe(³He, d)¹³⁷Cs was measured to be 1918 ± 12 keV.     

Asymmetric synthesis of the cis- and trans-stereoisomers of 4-aminopyrrolidine-3-carboxylic acid and 4-aminotetrahydrofuran-3-carboxylic acid

The diastereoselective conjugate addition of lithium (S)-N-benzyl-N-[small alpha]-methylbenzylamide has been successfully applied to the first asymmetric syntheses of cis-(3S,4R)- and trans-(3R,4R)-4-aminotetrahydrofuran-3-carboxylic acids (26% and 25% overall yield respectively, >98% d.e. and >97% e.e. in each case). Furthermore, the most efficient asymmetric synthesis to date of cis-(3R,4R)- and trans-(3R,4S)-4-aminopyrrolidine carboxylic acids is delineated: for cis-(3R,4R), four steps, >98% d.e., 52% overall yield; for trans-(3R,4S), five steps, >98% d.e., 50% overall yield.     

Direct observation of the protonation state of an imino sugar glycosidase inhibitor upon binding

Glycosidases are some of the most ubiquitous enzyme in nature. Their biological significance, coupled to their enormous catalytic prowess derived from tight binding of the transition state, is reflected in their importance as therapeutic targets. Many glycosidase inhibitors are known. Imino sugars are often potent inhibitors, yet many facets of their mode of action, such as their degree, if any, of transition-state "mimicry" and their protonation state when bound to the target glycosidase remain unclear. Atomic resolution analysis of the endoglucanase, Cel5A, in complex with a cellobio-derived isofagomine in conjunction with the pH dependence of Ki and kcat/KM reveals that this compound binds as a protonated sugar. Surprisingly, both the enzymatic nucleophile and the acid/base are unprotonated in the complex.     

Fourier transform infrared studies of alternate acid-amine Langmuir-Blodgett films with pyroelectric properties

FTIR-RAIRS and ATR techniques are shown to provide a powerful means of investigating the molecular behaviour responsible for the pyroelectric properties of organic monolayer assemblies on silicon and aluminised glass. Spectral changes, associated with either proton transfer or head group rearrangement, are well correlated with the level of pyroelectric response for two different devices. The technique promises to be extremely important for the elucidation of the microscopic properties of molecular electronic devices.     

Heteronuclear Nickel‐Iron Complexes and the Crystal Structure of [Fe2(CO)6(μ3‐S)2{Ni(dppe)}]

A series of heteronuclear nickel‐iron complexes [Fe₂(CO)₆(μ‐SH)(μ₃‐S){NiCl(PPh₃)₂}] ( 1 ), [Fe₂(CO)₆(μ‐SH)(μ₃‐S){NiCl(dppe)}] ( 2 ), [Fe₂(CO)₆(μ₃‐S)₂{Ni(PPh₃)₂}] ( 3 ), [Fe₂(CO)₆(μ₃‐S)₂{Ni(dppe)}] ( 4 ) and [Fe₂(CO)₆(μ‐SPh)(μ₃‐S){NiCl(dppe)}] ( 5 ) have been prepared. The structure of 4 has been determined by X‐ray crystallography. The central metal‐sulfur core of 4 has a trigonal bipyramidal shape with a NiFe₂ base plane with two axial sulfur atoms. Each iron atom is 5‐coordinate forming a distorted square pyramid; the nickel is square planar coordinated by two sulfur atoms and two phosphorus atoms.