Determination of Deuterated Phenylalanine and Tyrosine in Egg Protein by GCQ

In order to study protein digestibility by means of noninvasive tracer techniques (stable isotopes), a representative oral tracer, i.e. a stable isotope labeled protein, is needed. Therefore, egg white containing L-[ring-²H₅]phenylalanine and L-[ring-²H₄]tyrosine was prepared. The aim of this study was to measure the isotopic enrichment of the labeled amino acids in the egg white. The use of a standard GC-MS, based on ion trap technology was found to be a reliable technique. The enrichment of L-[ring-²H₅]phenylalanine and L-[ring-²H₄]tyrosine, expressed in Molar Percent (MP) amounted to 23.2 MP and 2.8 MP respectively.     

Fenchone Derivatives as a Novel Class of CB2 Selective Ligands: Design,Synthesis, X-ray Structure and Therapeutic Potential

A series of novel cannabinoid-type derivatives were synthesized by the coupling of (1S,4R)-(+) and (1R,4S)-(−)-fenchones with various resorcinols/phenols. The fenchone-resorcinol derivatives were fluorinated using Selectfluor and demethylated using sodium ethanethiolate in dimethylformamide (DMF). The absolute configurations of four compounds were determined by X-ray single crystal diffraction. The fenchone-resorcinol analogs possessed high affinity and selectivity for the CB2 cannabinoid receptor. One of the analogues synthesized, 2-(2′,6′-dimethoxy-4′-(2″-methyloctan-2″-yl)phenyl)-1,3,3-trimethylbicyclo[2.2.1]heptan-2-ol (1d), had a high affinity (K_i = 3.51 nM) and selectivity for the human CB2 receptor (hCB2). In the [³⁵S]GTPγS binding assay, our lead compound was found to be a highly potent and efficacious hCB2 receptor agonist (EC₅₀ = 2.59 nM, E_(max) = 89.6%). Two of the fenchone derivatives were found to possess anti-inflammatory and analgesic properties. Molecular-modeling studies elucidated the binding interactions of 1d within the CB2 binding site.     

Mutually exclusive hole and electron transfer coupling in cross stacked acenes

The topology of frontier molecular orbitals (FMOs) induces highly sensitive charge transfer coupling with variation in the intermolecular arrangement. A consistent optoelectronic property correlated to a specific aggregate architecture independent of the nature of the monomer is a rare phenomenon. Our theoretical investigation on stacked dimeric systems of linear [n]acenes (n = 2–5) and selected non-linear acenes with a D_2h point group reveals that the Greek cross (+) stacked orientation, irrespective of the molecular candidate, exhibits mutually exclusive hole and electron transfer couplings. The deactivation of either hole or electron transfer coupling is a consequence of the zero inter-orbital overlap between the highest occupied molecular orbitals (HOMOs) or lowest unoccupied molecular orbitals (LUMOs) of the monomers possessing gerade symmetry. In the Greek cross (+) stacked alignment, the (4n + 2) π-electronic acene systems with an odd number of benzenoids exhibit exclusive electron transfer coupling, while the even numbered acenes exhibit selective hole transfer coupling. The trend is reversed for representative 4n π-electronic acene systems. The effect of mutually exclusive charge transfer coupling in the hopping regime of charge transport was evaluated using semiclassical Marcus theory, and selective charge carrier mobility was exhibited by the Greek cross (+) stacks of the considered acene candidates. Additionally, the characteristic charge transfer coupling of the orthogonal acene stacks resulted in negligible short-range exciton coupling, inciting null exciton splitting at short interplanar distances. Engineering chromophores in precise angular orientations ensuring characteristic emergent properties can have tremendous potential in the rational design of advanced optoelectronic materials.

Acenes in the Greek cross (+) stack orientation exhibit selective hole and electron transfer coupling based on gerade symmetry in frontier molecular orbitals.     

List Coloring of Random and Pseudo-Random Graphs

choice number of a graph G is the minimum integer k such that for every assignment of a set S(v) of k colors to every vertex v of G, there is a proper coloring of G that assigns to each vertex v a color from S(v). It is shown that the choice number of the random graph G(n, p(n)) is almost surely whenever . A related result for pseudo-random graphs is proved as well. By a special case of this result, the choice number (as well as the chromatic number) of any graph on n vertices with minimum degree at least in which no two distinct vertices have more than common neighbors is at most . Received: October 13, 1997     

Acyclic edge colorings of graphs

A proper coloring of the edges of a graph G is called acyclic if there is no 2‐colored cycle in G. The acyclic edge chromatic number of G, denoted by a′(G), is the least number of colors in an acyclic edge coloring of G. For certain graphs G, a′(G) ≥ Δ(G) + 2 where Δ(G) is the maximum degree in G. It is known that a′(G) ≤ 16 Δ(G) for any graph G. We prove that there exists a constant c such that a′(G) ≤ Δ(G) + 2 for any graph G whose girth is at least cΔ(G) log Δ(G), and conjecture that this upper bound for a′(G) holds for all graphs G. We also show that a′(G) ≤ Δ + 2 for almost all Δ‐regular graphs. © 2001 John Wiley & Sons, Inc. J Graph Theory 37: 157–167, 2001     

S‐Functionalized Cysteine: Powerful Ligands for the Labelling of Bioactive Molecules with Triaquatricarbonyltechnetium‐99m(1+) ([99mTc(OH2)3(CO)3]+)

S‐Alkylated cysteines are used as efficient tridentate N,O,S‐donor‐atom ligands for the fac‐[M(CO)₃]⁺ moiety (M=^99mTc or Re). Reaction of (Et₄N)₂[ReBr₃(CO)₃] ( 3 ) with the model S‐benzyl‐L ‐cysteine ( 2 ) leads to the formation of [Re( 2′ )(CO)₃] ( 4 ) as the exclusive product ( 2′ =C‐terminal anion of 2 ). The tridentate nature of the alkylated cysteine in 4 was established by X‐ray crystallography. Compound 2 reacts with [^99mTc(OH₂)₃(CO)₃]⁺ under mild conditions (10⁻⁴ M , 50°, 30 min) to afford [^99mTc( 2′ )(CO)₃] ( 5 ) and represents, therefore, an efficient chelator for the labelling of biomolecules. L ‐Cysteine, S‐alkylated with a 3‐aminopropyl group (→ 7 ), was conjugated via a peptide coupling sequence with Coα‐[α‐(5,6‐dimethyl‐1H‐benzimidazolyl)]‐Coβ‐cyanocobamic b‐acid ( 6 ), the b‐acid of cyanocob(III)alamin (vitamin B₁₂) (Scheme 3). More convenient was a one‐pot procedure with a derivative of vitamin B₁₂ comprising a free amine group at the b‐position. This amine 15 was treated with NHS (N‐hydroxysuccinimide)‐activated 1‐iodoacetic acid 14 to introduce an I‐substituent in vitamin B₁₂. Subsequent addition of unprotected L ‐cysteine resulted in nucleophilic displacement of the I‐atom by the S‐substituent, affording the vitamin B₁₂ alkylated cysteine fragment 17 (Scheme 4). The procedure was quantitative and did not require purification of intermediates. Both cobalamin–cysteine conjugates could be efficiently labelled with [^99mTc(OH₂)₃(CO)₃]⁺ ( 1 ) under conditions identical to those of the model complex 5 . Biodistribution studies of the cobalamin conjugates in mice bearing B10‐F16 melanoma tumors showed a tumor uptake of 8.1±0.6% and 4.4±0.5% injected dose per gram of tumor tissue after 4 h and 24 h, respectively (Table 1).     

N(epsilon) functionalization of metal and organic protected L-histidine for a highly efficient,direct labeling of biomolecules with [Tc(OH2)3(CO)3]+

Two different pathways for the introduction of an acetyl group at N(epsilon ) in a N(alpha), N(delta), and -COO protected histidine to afford N(epsilon)-(CH(2)COOH)-histidine derivative 7 b are presented. The purpose of this study is the coupling of 7 b to amino groups in bioactive molecules such as peptides. After full deprotection of such a bioconjugate, histidine provides three coordination sites which efficiently coordinate to [(99m)Tc(OH(2))(3)(CO)(3)](+) or [Re(OH(2))(3)(CO)(3)](+) in a facial geometry. This allows the development of novel radiopharmaceuticals. Selective derivatization at the N(epsilon) position has conveniently been achieved by concomitant protection of N(alpha) and N(delta) with a carbonyl group forming a six-membered urea. Cyclic urea ring opening with Fm-OH, coupling of phenylalanine as a model to 7 b through its primary amine and removing of all protecting groups in one step gave a histidine derivative of phenylalanine which could be labeled at 10(-5) M with (99m)Tc in very high yield and even in about 50 % yield at 10(-6) M. The Xray structure of a complex with [Re(CO)(3)](+) in which anilin is coupled to 7 b confirms the facial arrangement of histidine. A second pathway applies directly the [Re(CO)(3)](+) moiety as a protecting group. This is one of the rare examples in which a metal fragment is used as a protecting group for organic functionalities. The coordination to histidine protects the N(alpha), N(delta) and COO group in one single step, subsequent alkylation with BrCH(2)COOH(R) at N(epsilon), coupling to phenylalanine and oxidative deprotection of [Re(CO)(3)](+) to [ReO(4)](-) gave the corresponding bioconjugate in which histidine is coupled to phenylalanine through an acetylamide at N(epsilon). Both methods offer convenient pathways to introduce histidine in a biomolecule under retention of its three coordination sites. The procedures are adaptable to any biomolecule with pendant amines and allow the development of novel radiopharmaceuticals or inversed peptides.     

Exact and approximate solutions to the one-center McMurchie–Davidson tree-search problem

We have attempted to optimize the cost (the total number of floating-point operations required) of using the McMurchie–Davidson R_NLMj recurrence relation. Rigorous solutions of the tree-search problem inherent in the cost minimization are given for total angular momentum L ≤ 7. For L ≥ 8, the rigorous search algorithm is prohibitively expensive, and we propose an approximate algorithm that generates highly optimized trees. Cost comparisons demonstrate that the present scheme is consistently superior to two others currently in use.     

Synthesis and characterization of two quaternary thorium chalcophosphates: Cs4Th2P6S18 and Rb7Th2P6Se21

Two new thorium chalcophosphates have been synthesized by the reactive flux method and characterized by single-crystal X-ray diffraction, diffuse reflectance, and Raman spectroscopy: Cs4Th2P6S18 (I); Rb7Th2P6Se21 (II). Compound I crystallizes as colorless blocks in the triclinic space group P1 (No. 2) with a = 12.303(4) A, b = 12.471(4) A, c = 12.541(4) A, alpha = 114.607(8) degrees, beta = 102.547(6) degrees, gamma = 99.889(7) degrees, and Z = 2. The structure consists of (Th2P6S18)(4-) layers separated by layers of cesium cations and only contains the (P2S6)(4-) building block. Compound II crystallizes as red blocks in the triclinic space group P1 (No. 2) with a = 11.531(3) A, b = 12.359(4) A, c = 16.161(5) A, alpha = 87.289(6) degrees, beta = 75.903(6) degrees, gamma = 88.041(6) degrees, and Z = 2. The structure consists of linear chains of (Th2P6Se21)(7-) separated by rubidium cations. Compound II contains both the (PSe4)(3-) and (P2Se6)(4-) building blocks. Both structures may be derived from two known rare earth structures where a rare earth site is replaced by an alkali or actinide metal to form these novel structures. Optical band gap measurements show that compound I has a band gap of 2.8 eV and compound II has a band gap of 2.0 eV. Solid-state Raman spectroscopy of compound I shows the vibrations expected for the (P2S6)(4-) unit. Raman spectroscopy of compound II shows the vibrations expected for both (PSe4)(3-) and (P2Se6)(4-) units. Our work shows the remarkable diversity of the actinide chalcophosphate system and demonstrates the phase space is still ripe to discover new structures.