BIAN-Aluminium-Catalysed Imine Hydrogenation.

Hydrogenations have been dominated by transition metal catalysis, while the use of more abundant and inexpensive main group metal catalysts has remained a great challenge. Here, a bimetallic Li/Al dihydride was successfully applied to catalytic hydrogenations of imines. The catalyst [(DippBIAN)Al(µ-H)2Li(OEt2)2] was easily prepared from the 2e-reduced BIAN derivative and LiAlH4.

Combined Photoredox and Iron Catalysis for the Cyclotrimerization of Alkynes.

Successful combinations of visible-light photocatalysis with metal catalysis have recently enabled the development of hitherto unknown chemical reactions. Dual mechanisms from merging metal-free photocatalysts and earth-abundant metal catalysts are still in their infancy. We report a photo-organo-iron-catalyzed cyclotrimerization of alkynes by photoredox activation of a ligand-free Fe catalyst. The reaction operates under very mild conditions (visible light, 20 °C, 1 h) with 1-2 mol % loading of the three catalysts (dye, amine, FeCl2 ).

Synthesis of 7ß-hydroxy-8-ketone opioid derivatives with antagonist activity at mu- and delta-opioid receptors.

Despite extensive years of research, the direct oxidation of the 7,8-double bond of opioids has so far received little attention and knowledge about the effects of this modification on activity at the different opioid receptors is scarce. We herein report that potassium permanganate supported on iron(II) sulfate heptahydrate can be used as a convenient oxidant in the one-step, heterogeneous conversion of Δ7,8-opioids to the corresponding 7ß-hydroxy-8-ketones. Details of the reaction mechanism are given and the effects of the substituent at position 6 of several opioids on the reaction outcome is discussed. The opioid hydroxy ketones prepared are antagonists at the mu- and delta-opioid receptors. Docking simulations and detailed structure-activity analysis revealed that the presence of the 7ß-hydroxy-8-ketone functionality in the prepared compounds can be used to gain activity towards the delta opioid receptor. The 7ß-hydroxy-8-ketones prepared with this method can also be regarded as versatile intermediates for the synthesis of other opioids of interest.

Spin state variability in Fe2+ complexes of substituted (2-(pyridin-2-yl)-1,10-phenanthroline) ligands as versatile terpyridine analogues.

Fe2+ spin crossover complexes [Fe(L)2]2+ (L = 2-(6-R1-pyridin-2-yl)-1,10-phenanthroline with R1 = H, methoxy, bromo, -(1H-pyrazol-1-yl) or L = 2-(3-methoxy-pyridin-2-yl)-1,10-phenanthroline) were prepared. These air stable and durable complexes show SCO behaviour with very different transition temperatures T1/2 ranging from 130 K to 600 K depending on the substitution pattern. The use of 1H NMR spectroscopy to elucidate the thermodynamics and kinetics of SCO in a solution of this series is described in detail. By introduction of an additional pyrazole donor (R1) in the ortho-position to the pyridine, the N6 octahedral coordination sphere is expanded to N8 coordination with a trigonal dodecahedral structure. This leads to a strong stabilization of the high spin state and an increased longitudinal relaxation R1 of the proton spins. The larger R1 values were ascribed to different electronic structures with non-orbital degenerate quintet ground states and a larger energetic separation from the first excited state. These results are also supported by Mössbauer spectroscopy. The N8 coordination sphere stabilizes the complex in the high spin state and no indication for SCO was found. DFT calculations confirmed the experimentally obtained order of T1/2 and allowed the calculation of the complex structure in experimentally non-accessible spin states. Complexes of this series can be oxidized to the Fe3+ complexes in a chemically reversible fashion. Interestingly, the lowest oxidation potential was observed for the N8 coordinated complex.

(1)H NMR spectroscopic elucidation in solution of the kinetics and thermodynamics of spin crossover for an exceptionally robust Fe(2+) complex.

A series of Fe(2+) spin crossover (SCO) complexes [Fe(5/6)](2+) employing hexadentate ligands (5/6) with cis/trans-1,2-diamino cyclohexanes (4) as central building blocks were synthesised. The ligands were obtained by reductive amination of 4 with 2,2'-bipyridyl-6-carbaldehyde or 1,10-phenanthroline-2-carbaldehyde 3. The chelating effect and the rigid structure of the ligands 5/6 lead to exceptionally robust Fe(2+) and Zn(2+) complexes conserving their structure even in coordinating solvents like dmso at high temperatures. Their solution behavior was investigated using variable temperature (VT) (1)H NMR spectroscopy and VT Vis spectroscopy. SCO behavior was found for all Fe(2+) complexes in this series centred around and far above room temperature. For the first time we have demonstrated that the thermodynamics as well as kinetics for SCO can be deduced by using VT (1)H NMR spectroscopy. An alternative scheme using a linear correction term C(1) to model chemical shifts for Fe(2+) SCO complexes is presented. The rate constant for the SCO of [Fe(rac-trans-5)](2+) obtained by VT (1)H NMR was validated by Laser Flash Photolysis (LFP), with excellent agreement (1/(kHL + kLH) = 33.7/35.8 ns for NMR/LFP). The solvent dependence of the transition temperature T1/2 and the solvatochromism of complex [Fe(rac-trans-5)](2+) were ascribed to hydrogen bond formation of the secondary amine to the solvent. Enantiomerically pure complexes can be prepared starting with R,R- or S,S-1,2-diaminocyclohexane (R,R-trans-4 or S,S-trans-4). The high robustness of the complexes reduces a possible ligand scrambling and allows preparation of quasiracemic crystals of [Zn(R,R-5)][Fe(S,S-5)](ClO4)4·(CH3CN) composed of a 1 : 1 mixture of the Zn and Fe complexes with inverse chirality.

Crystal structure of an unknown tetra-hydro-furan solvate of tetra-kis-(µ 3-cyanato-κ(3) N:N:N)tetra-kis-[(triphenyl-phosphane-κP)-silver(I)].

In the title compound, [{[(C6H5)3P]Ag}4{NCO}4], a distorted Ag4N4-heterocubane core is set up by four Ag(I) ions being coordinated by the N atoms of the cyanato anions in a µ 3-bridging mode. In addition, a tri-phenyl-phosphine ligand is datively bonded to each of the Ag(I) ions. Intra-molecular Ag⋯Ag distances as short as 3.133 (9) Šsuggest the presence of argentophilic (d (10)⋯d (10)) inter-actions. Five moderate-to-weak C-H⋯O hydrogen-bonding inter-actions are observed in the crystal structure, spanning a three-dimensional network. A region of electron density was treated with the SQUEEZE procedure in PLATON [Spek (2015). Acta Cryst. C71, 9-18] following unsuccessful attempts to model it as being part of disordered tetra-hydro-furan solvent mol-ecules. The given chemical formula and other crystal data do not take into account these solvent mol-ecules.

Crystal structure of an unknown solvate of bis-(tetra-n-butyl-ammonium) [N,N'-(4-tri-fluoro-methyl-1,2-phenyl-ene)bis-(oxamato)-κ(4) O,N,N',O']nickelate(II).

In the title compound, [N(C4H9)4]2[Ni(C11H3F3N2O6)] or [N(n-Bu)4]2[Ni(topbo)] [n-Bu = n-butyl and topbo = 4-tri-fluoro-methyl-1,2-phenyl-enebis(oxamate)], the Ni(2+) cation is coordinated by two deprotonated amido N atoms and two carboxyl-ate O atoms, setting up a slightly distorted square-planar coordination environment. The [Ni(topbo](2-) anion lies on a twofold rotation axis. Due to an incompatibility with the point-group symmetry of the complete mol-ecule, orientational disorder of the CF3 group is observed. The tetra-hedral ammonium cations and the anion are linked by weak inter-molecular C-H⋯O and C-H⋯F hydrogen-bonding inter-actions into a three-dimensional network. A region of electron density was treated with the SQUEEZE procedure in PLATON [Spek (2015). Acta Cryst. C71, 9-18] following unsuccessful attempts to model it as plausible solvent mol-ecule(s). The given chemical formula and other crystal data do not take into account the unknown solvent mol-ecule.

Magnetic superexchange interactions: trinuclear bis(oxamidato) versus bis(oxamato) type complexes.

The diethyl ester of o-phenylenebis(oxamic acid) (opbaH2Et2) was treated with an excess of RNH2 in MeOH to cause the exclusive formation of the respective o-phenylenebis(N(R)-oxamides) (opboH4R2, R = Me , Et , (n)Pr ) in good yields. Treatment of with half an equivalent of [Cu2(AcO)4(H2O)2] or one equivalent of [Ni(AcO)2(H2O)4] followed by the addition of four equivalents of [(n)Bu4N]OH resulted in the formation of mononuclear bis(oxamidato) type complexes [(n)Bu4N]2[M(opboR2)] (M = Ni, R = Me , Et , (n)Pr ; M = Cu, R = Me , Et , (n)Pr ). By addition of two equivalents of [Cu(pmdta)(NO3)2] to MeCN solutions of , novel trinuclear complexes [Cu3(opboR2)(L)2](NO3)2 (L = pmdta, R = Me , Et , (n)Pr ) could be obtained. Compounds have been characterized by elemental analysis and NMR/IR spectroscopy. Furthermore, the solid state structures of and have been determined by single-crystal X-ray diffraction studies. By controlled cocrystallization, diamagnetically diluted and (1%) in the host lattice of and (99%) (@ and @), respectively, in the form of single crystals have been made available, allowing single crystal ESR studies to extract all components of the g-factor and the tensors of onsite (Cu)A and transferred (N)A hyperfine (HF) interaction. From these studies, the spin density distribution of the [Cu(opboEt2)](2-) and [Cu(opbo(n)Pr2)](2-) complex fragments of and , respectively, could be determined. Additionally, as a single crystal ENDOR measurement of @ revealed the individual HF tensors of the N donor atoms to be unequal, individual estimates of the spin densities on each N donor atom were made. The magnetic properties of were studied by susceptibility measurements versus temperature to give J values varying from -96 cm(-1) () over -104 cm(-1) () to -132 cm(-1) (). These three trinuclear Cu(II)-containing bis(oxamidato) type complexes exhibit J values which are comparable to and slightly larger in magnitude than those of related bis(oxamato) type complexes. In a summarizing discussion involving experimentally obtained ESR results (spin density distribution) of and , the geometries of the terminal [Cu(pmdta)](2+) fragments of determined by crystallographic studies, together with accompanying quantum chemical calculations, an approach is derived to explain these phenomena and to conclude if the spin density distribution of mononuclear bis(oxamato)/bis(oxamidato) type complexes could be a measure of the J couplings of corresponding trinuclear complexes.

Crystal structure of cyclo-bis-(µ4-2,2-di-allyl-malonato-κ(6) O (1),O (3):O (3):O (1'),O (3'):O (1'))tetra-kis-(triphenyl-phosphane-κP)tetra-silver(I).

In the tetra-nuclear mol-ecule of the title compound, [Ag4(C9H10O4)2(C18H15P)4], the Ag(I) ion is coordinated by one P and three O atoms in a considerably distorted tetra-hedral environment. The two 2,2-di-allyl-malonate anions bridge four Ag(I) ions in a µ4-(κ(6) O (1),O (3):O (3):O (1'),O (3'):O (1')) mode, setting up an Ag4O8P4 core (point group symmetry -4..) of corner-sharing tetra-hedra. The shortest intra-molecular Ag⋯Ag distance of 3.9510 (3) Šreveals that no direct d (10)⋯d (10) inter-actions are present. Four weak intra-molecular C-H⋯O hydrogen bonds are observed in the crystal structure of the title compound, which most likely stabilize the tetra-nuclear silver core.

Tin Oxide Nanoparticles and SnO2 /SiO2 Hybrid Materials by Twin Polymerization Using Tin(IV) Alkoxides.

Twin polymerization was used to prepare composite materials composed of SnO2 nanoparticles entrapped in a polymer matrix. Novel, well-defined tin-containing molecular precursors, so-called twin monomers, were synthesized by transesterification starting from Sn(OR)4 (R=tBu, tAm) to give Sn(OCH2 C4 H3 O)4 (1), [Sn(OCH2 C4 H3 S)4 ⋅HOCH2 C4 H3 S]2 (2), [Sn(OCH2 -2-OCH3 C6 H4 )4 ⋅HOCH2 -2-OCH3 C6 H4 ]2 (3), [Sn(OCH2 -2,4-(OCH3 )2 C6 H3 )4 ⋅HOCH2 -2,4-(OCH3 )2 C6 H3 ]2 (4), 2,2'-spirobi[4H-1,3,2-benzodioxastannine] (5), 2,2'-spirobi[6-methylbenzo(4H-1,3,2)-dioxastannine] (6), and 2,2'-spirobi[6-methoxybenzo(4H-1,3,2)dioxastannine] (7). 13 C and 119 Sn NMR spectroscopy in the solid state and in solution as well as IR spectroscopy and elemental analysis were used to characterize the tin alkoxides. The molecular structures of compounds 2 and 3 were determined by single-crystal X-ray diffraction analysis. The moisture sensitivity of the tin(IV) alkoxides was demonstrated by the formation of the tin oxocluster [Sn3 (µ3 -O)(µ2 -OH)(µ2 -OCH2 C4 H3 S)3 (OCH2 C4 H3 S)6 (HOCH2 C4 H3 S)]2 (2 a), a hydrolysis product of compound 2. Polymerization reactions in the melt (for 1 and 5) and in solution (for 2-4) resulted in cross-linked nanocomposites of the type polymer/SnO2 . Subsequent oxidation of the composites gave SnO2 with BET surface areas up to 178 m2 g-1 . Simultaneous twin polymerization of compounds 5-7 with the silicon derivative 2,2'-spirobi[4H-1,3,2-benzodioxasiline] resulted in the formation of polymer/SnO2 /SiO2 hybrid materials. Oxidation gave porous materials with SnO2 nanoparticles embedded in a silica network with BET surface areas up to 378 m2 g-1 . The silica acts as a crystal growth inhibitor, which prevents sintering of the SnO2 nanoparticles 20-32 nm in size.

Phosphino imidazoles and imidazolium salts for Suzuki C-C coupling reactions.

The consecutive syntheses of imidazoles 1-(4-X-C(6)H(4))-4,5-R(2)-(c)C(3)HN(2) (3a, X = Br, R = H; 3b, X = I, R = Me; 3c, X = H, R = Me; 5, X = Fc, R = H; 7, X = C≡CFc, R = H; 9, X = C(6)H(5), R = Me; Fc = Fe(η(5)-C(5)H(4))(η(5)-C(5)H(5))), phosphino imidazoles 1-(4-X-C(6)H(4))-2-PR'(2)-4,5-R(2)-(c)C(3)N(2) (11a-k; X = Br, I, Fc, FcC≡C, Ph; R = H, Me; R' = Ph, (c)C(6)H(11), (c)C(4)H(3)O), imidazolium salts [1-(4-X-C(6)H(4))-3-R''-4,5-R(2)-(c)C(3)HN(2)]I (16a; X = Br, R = H, R'' = n-Bu; 16b, X = Br, R = H, R'' = n-C(8)H(17); 16c, X = I, R = Me, R'' = n-C(8)H(17), 16d, X = H, R = Me, R'' = n-C(8)H(17)) and phosphino imidazolium salts [1-C(6)H(5)-2-PR'(2)-3-n-C(8)H(17)-4,5-Me(2)-(c)C(3)N(2)]PF(6) (17a, R' = C(6)H(5); 17b, R' = (c)C(6)H(11)) or [1-(4-P(C(6)H(5))(2)-C(6)H(4))-3-n-C(8)H(17)-4,5-Me(2)-(c)C(3)HN(2)]PF(6), (20) and their selenium derivatives 1-(4-X-C(6)H(4))-2-P([double bond, length as m-dash]Se)R'(2)-4,5-R(2)-(c)C(3)N(2) (11a-Se-f-Se; X = Br, I; R = H, Me; R' = C(6)H(5), (c)C(6)H(11), (c)C(4)H(3)O) are reported. The structures of 11a-Se and [(1-(4-Br-C(6)H(4))-(c)C(3)H(2)N(2)-3-n-Bu)(2)PdI(2)] (19) in the solid state were determined. Cyclovoltammetric measurements were performed with the ferrocenyl-containing molecules 5 and 7 showing reversible redox events at E(0) = 0.108 V (ΔE(p) = 0.114 V) (5) and E(0) = 0.183 V (ΔE(p) = 0.102 V) (7) indicating that 7 is more difficult to oxidise. Imidazole oxidation does not occur up to 1.3 V in dichloromethane using [(n-Bu)(4)N][B(C(6)F(5))(4)] as supporting electrolyte, whereas an irreversible reduction is observed between -1.2 - -1.5 V. The phosphino imidazoles 11a-k and the imidazolium salts 17a,b and 20, respectively, were applied in the Suzuki C-C cross-coupling of 2-bromo toluene with phenylboronic acid applying [Pd(OAc)(2)] as palladium source. Depending on the electronic character of 11a-k, 17a,b and 20 the catalytic performance of the in situ generated catalytic active species can be predicted. As assumed, more electron-rich phosphines with their higher donor capability show higher activity and productivity. Additionally, 11e was applied in the coupling of 4-chloro toluene with phenylboronic acid showing an excellent catalytic performance when compared to catalysts used by Fu, Beller and Buchwald. Furthermore, 11e is eligible for the synthesis of sterically hindered biaryls under mild reaction conditions. C-C Coupling reactions with the phosphino imidazolium salts 17b and 20 in ionic liquids [BMIM][PF(6)] and [BDMIM][BF(4)] were performed, showing less activity than in common organic solvents.

1,4-Dihydro-benzo[g]quinoxaline-2,3-dione.

The title compound, C12H8N2O2, was prepared by the reaction of the diethyl ester of naphthalene-bis-(oxamate) with tert-BuNH2. The mol-ecule is nearly planar, with an r.m.s. deviation of 0.017 Šfrom the plane through all 16 non-H atoms. In the crystal, a three-dimensional network is formed, composed of layers of mol-ecules along the b- and c-axis directions, due to the formation of inter-molecular N-H⋯O hydrogen bonds, as well as of chains along the a-axis direction due to parallel displaced sandwich-type π-π inter-actions with average distances between the inter-acting mol-ecules in the range 3.35-3.40 Å.

From {Bi22O26} to chiral ligand-protected {Bi38O45}-based bismuth oxido clusters.

The reaction of [Bi(22)O(26)(OSiMe(2)tBu)(14)] (1) in THF with salicylic acid gave [Bi(22)O(24)(HSal)(14)] (2) first, which was converted into [Bi(38)O(45)(HSal)(22)(OH)(2)(DMSO)(16.5)]·DMSO·H(2)O (3·DMSO·H(2)O) after dissolution and crystallization from DMSO. Single-crystal X-ray diffraction analysis and ESI mass spectrometry associated with infrared multi-photon dissociation (IRMPD) tandem MS experiments confirm the formation of the large and quite stable bismuth oxido cluster 3. The reaction of compound 2 with the butoxycarbonyl(BOC)-protected amino acids phenylalanine and valine (BOC-PheOH and BOC-ValOH), respectively, resulted in the formation of chiral [Bi(38)O(45)(BOC-AA)(22)(OH)(2)] (AA=deprotonated amino acid), as shown by a combination of different analytical techniques such as elemental analysis, dynamic light scattering, circular dichroism spectroscopy, and ESI mass spectrometry.

Influence of electron delocalization in heterocyclic core systems on the electrochemical communication in 2,5-di- and 2,3,4,5-tetraferrocenyl thiophenes, furans, and pyrroles.

A series of 2,5-di- and 2,3,4,5-tetraferrocenyl-substituted thiophenes, furans, and pyrroles were synthesized using the Negishi C,C cross-coupling protocol. The electronic and electrochemical properties of these compounds were investigated by cyclic voltammetry (CV), square wave voltammetry (SWV), and in situ UV-vis/NIR spectroscopy. The molecular structures of 2,5-diferrocenyl furan and 2,3,4,5-tetraferrocenyl-1-methyl-1H-pyrrole in the solid state are discussed. The ferrocenyls could sequentially be oxidized giving two or four reversible responses for the appropriate di- or tetraferrocenyl-substituted heterocyclic molecules. The observed ΔE°' values range between 186 and 450 mV. The NIR measurements confirm electronic communication as intervalence charge transfer (IVCT) absorptions were found in the corresponding mono- and in case of the tetraferrocenyl compounds also in the dicationic species. All compounds, except tetraferrocenyl thiophene (a class I system), were classified as class II systems according to Robin and Day. They show a linear relationship between ΔE°' and the IVCT oscillator strength f which could be shown for the first time in organometallic chemistry. This was possible because the series of molecules exhibit analogous geometries and hence, similar electrostatic properties. This correlation was confirmed by electro- and spectro-electrochemical measurements. Within these studies a new approach for the estimation of the effective electron transfer distances r(ab) is discussed.

Highly strained 2,3-bridged 2H-azirines at the borderline of closed-shell molecules.

Substituted 1-azidocyclopentenes and 1-azidocyclohexenes were photolyzed to generate 2,3-bridged 2H-azirines. In the case of bridgehead azirines with a six-membered carbocycle, detection by NMR spectroscopic analysis was possible, whereas even kinetically stabilized bridgehead azirines with a five-membered ring could not be characterized by low-temperature NMR spectroscopic analysis. Thus, a recent report on the latter heterocycles was corrected. Depending on the substitution pattern, irradiation of 1-azidocyclopentenes either led to products that can be explained on the basis of short-lived 2,3-bridged 2H-azirines, or gave secondary products generated from triplet nitrenes. The diverse photoreactivity of 2,3-bridged 2H-azirines was also studied by quantum chemical methods (DFT, CCSD(T), CASSCF(6,6)) with respect to the singlet and triplet energy surfaces. The ring-opening processes leading to the corresponding vinyl nitrenes were identified as key steps for the observed reactivity.

Elusive ethynyl azides: trapping by 1,3-dipolar cycloaddition and decomposition to cyanocarbenes.

Although they decompose rapidly to produce cyanocarbenes, ethynyl azides were generated from (chloroethynyl)arenes and trapped for the first time by 1,3-dipolar cycloaddition at cyclooctyne.

Investigation of the mutual pharmacokinetic interactions between bosentan, a dual endothelin receptor antagonist, and simvastatin.

BACKGROUND: In vitro, bosentan has been shown to be a mild inducer of cytochrome P450 (CYP) 2C9 and 3A4. PURPOSE: To investigate in vivo the mutual pharmacokinetic interactions between bosentan and simvastatin, a CYP3A4 substrate. METHODS: Nine healthy male subjects were treated in a three-period randomised crossover study with: (A) bosentan 125 mg twice daily for 5.5 days; (B) simvastatin 40 mg once daily for 6 days; and (C) bosentan 125 mg twice daily and simvastatin 40 mg once daily for 5.5 and 6 days, respectively. Plasma concentration-time profiles of bosentan and its metabolites (treatments A and C) and simvastatin and beta-hydroxyacid simvastatin (treatments B and C) were determined on day 6. RESULTS: Steady-state conditions for bosentan and its metabolites were attained on day 4 of treatment. The pharmacokinetic parameters of bosentan and its metabolites were not influenced by concomitant treatment with simvastatin: areas under the plasma concentration-time curve over one administration interval of 12 hours (AUC(tau)) [geometric mean and 95% CI] were 4586 (3719-5656) and 4928 (3945-6156) micro g * h/L. In contrast, bosentan significantly reduced exposure to simvastatin and beta-hydroxyacid simvastatin by 34 and 46%, respectively. AUC(tau) values for simvastatin were 30.5 (23.1-40.2) and 20.0 (15.9-25.1) micro g * h/L and for beta-hydroxyacid simvastatin 43.0 (32.1-57.8) and 23.4 (16.7-32.6) micro g * h/L in treatments B and C, respectively. CONCLUSIONS: Concomitant treatment with bosentan reduces the exposure to simvastatin and beta-hydroxyacid simvastatin by approximately 40%, indicating that in vivo bosentan is also a mild inducer of CYP3A4.

Pharmacokinetics of valganciclovir and ganciclovir in renal impairment.

BACKGROUND: Valganciclovir is the oral prodrug of ganciclovir. The pharmacokinetics of valganciclovir in patients with renal impairment is not known. Furthermore, it is not known whether there are any pharmacokinetic differences between patients who are positive for human immunodeficiency virus (HIV) and cytomegalovirus (CMV) and healthy subjects. METHODS: A total of 44 patients were included-18 with mild, medium, or severe renal impairment; 6 with end-stage renal disease who were on long-term hemodialysis; 8 HIV/CMV-positive patients with normal renal function; and 12 healthy subjects serving as controls. Valganciclovir and ganciclovir serum concentrations were measured after oral administration of 900 mg of valganciclovir. Pharmacokinetic parameters were estimated by means of noncompartmental and compartmental methods. RESULTS: After oral administration of the prodrug valganciclovir, ganciclovir bioavailability was 60% and ganciclovir concentrations were higher (maximum concentration [C(max)], 8.5 microg/mL versus 5.8 microg/mL) and appeared later (time to maximum concentration [T(max)], 4.3 versus 2.0 hours) in patients with severe renal impairment compared with healthy subjects. The elimination half-life (t(1/2)) of ganciclovir was longer in patients with renal failure (t(1/2) of 68.1 hours in patients with end-stage renal disease compared with 3.5 hours in healthy subjects). Ganciclovir clearance was correlated with creatinine clearance (r = 0.975). Hemodialysis removed 50% of ganciclovir. We observed no differences in pharmacokinetics between HIV/CMV-positive patients and healthy subjects. A 2-compartment model with zero-order input and first-order elimination proved to be the most appropriate model for ganciclovir after oral administration of valganciclovir. CONCLUSIONS: The dosage of valganciclovir has to be adjusted to the degree of renal impairment. Dosage adjustment is not necessary for HIV/CMV-positive patients.