Role of non-covalent and covalent interactions in cargo loading capacity and stability of polymeric micelles.

Polymeric micelles self-assembled from biodegradable amphiphilic block copolymers have been proven to be effective drug delivery carriers that reduce the toxicity and enhance the therapeutic efficacy of free drugs. Several reviews have been reported in the literature to discuss the importance of size/size distribution, stability and drug loading capacity of polymeric micelles for successful in vivo drug delivery. This review is focused on non-covalent and covalent interactions that are employed to enhance cargo loading capacity and in vivo stability, and to achieve nanosize with narrow size distribution. In particular, this review analyzes various non-covalent and covalent interactions and chemistry applied to introduce these interactions to the micellar drug delivery systems, as well as the effects of these interactions on micelle stability, drug loading capacity and release kinetics. Moreover, the factors that influence these interactions and the future research directions of polymeric micelles are discussed.

Synergistic co-delivery of membrane-disrupting polymers with commercial antibiotics against highly opportunistic bacteria.

A series of vitamin E-containing biodegradable antimicrobial cationic polycarbonates is designed and synthesized via controlled organocatalytic ring-opening polymerization. The incorporation of vitamin E significantly enhances antimicrobial activity. These polymers demonstrate broad-spectrum antimicrobial activity against various microbes, e.g., S. aureus (Gram-positive), E-coli (Gram-negative) and C. albicans (fungi). More importantly, the co-delivery of such polymers with selected antibiotics (e.g., doxycycline) shows high synergism towards difficult-to-kill bacteria P. aeruginosa. These findings suggest that these vitamin E-functionalized polycarbonates are potentially useful antimicrobial agents against challenging bacterial/fungal infections.

Reactivity studies of oxo-Mo(IV) complexes containing potential hydrogen-bond acceptor/donor phenolate ligands.

Reactivity studies of oxo-Mo(IV) complexes, Tp(iPr)MoO{2-OC(6)H(4)C(O)R-κ(2)O,O'} (R = Me, Et, OMe, OEt, OPh, NHPh), containing chelated hydrogen-bond donor/acceptor phenolate ligands are reported. Hydrolysis/oxidation of Tp(iPr)MoO(2-OC(6)H(4)CO(2)Ph-κ(2)O,O') in the presence of methanol yields tetranuclear [Tp(iPr)MoO(µ-O)(2)MoO](2)(µ-OMe)(2) (1), while condensation of Tp(iPr)MoO{2-OC(6)H(4)C(O)Me-κ(2)O,O'} and methylamine gives the chelated iminophenolate complex, Tp(iPr)MoO{2-OC(6)H(4)C(Me)NMe-κ(2)O,N} (2), rather than the aqua complex, Tp(iPr)MoO{2-OC(6)H(4)C(Me)NMe-κO}(OH(2)). The oxo-Mo(IV) complexes are readily oxidized by dioxygen or hydrogen peroxide to the corresponding cis-dioxo-Mo(VI) complexes, Tp(iPr)MoO(2){2-OC(6)H(4)C(O)R}; in addition, suitable one-electron oxidants, e.g., [FeCp(2)]BF(4) and [N(C(6)H(4)Br)(3)][SbCl(6)], oxidize the complexes to their EPR-active (g(iso) ≈ 1.942) molybdenyl counterparts (3, 4). Molybdenyl complexes such as Tp(iPr)MoOCl{2-OC(6)H(4)C(O)R} (5) and Tp(iPr)MoOCl(2) also form when the complexes react with chlorinated solvents. The ester derivatives (R = OMe, OEt, OPh) react with propylene sulfide to form cis-oxosulfido-Mo(VI) complexes, Tp(iPr)MoOS{2-OC(6)H(4)C(O)R}, that crystallize as dimeric µ-disulfido-Mo(V) species, [Tp(iPr)MoO{2-OC(6)H(4)C(O)R}](2)(µ-S(2)) (6-8). The crystal structures of [Tp(iPr)MoO(µ-O)(2)MoO](2)(µ-OMe)(2), Tp(iPr)MoO{2-OC(6)H(4)C(Me)NMe}, Tp(iPr)MoOCl{2-OC(6)H(4)C(O)NHPh}·{2-HOC(6)H(4)C(O)NHPh}, and [Tp(iPr)MoO{2-OC(6)H(4)C(O)R}](2)(µ-S(2)) (R = OMe, OEt) are reported.

Synthesis and characterization of TpiPrMoO(S2PR2) (R = Pri, Ph, OEt, OPri, (-)-mentholate) and {HB(OMe)(Pripz)2}MoO(S2PPri2), including isomers of known 1,2-borotropically-shifted complexes.

Green/blue TpiPrMoO(S2PR2) (TpiPr = hydrotris(3-isopropylpyrazolyl)borate; R = Pri, Ph, OEt, OPri, (-)-mentholate) complexes were synthesized and characterized by elemental analysis, mass spectrometry, IR and NMR spectroscopy, and X-ray crystallography. The diamagnetic, six-coordinate, oxo-Mo(IV) complexes possess distorted octahedral geometries defined by terminal oxo, bidentate dithio acid, and tridentate TpiPr ligands. The R = Pri and Ph derivatives are isomers of previously reported 1,2-borotropically shifted complexes, TpiPr*MoO(S2PR2) (TpiPr* = hydrobis(3-isopropylpyrazolyl)(5-isopropylpyrazolyl)borate; ref: Inorg. Chem. 1996, 35, 5368). Conversion of TpiPrMoO(S2PPh2) into TpiPr*MoO(S2PPh2) at elevated temperatures (>80 degrees C) showed that the borotropically shifted isomer was thermodynamically more stable than the unshifted species. Reaction with methanol converts TpiPrMoO(S2PPri2) into {HB(OMe)(Pripz)2}MoO(S2PPri2) (Pripz = 3-isopropylpyrazolyl), which was characterized by spectroscopic and crystallographic methods.

Toward multifunctional Mo(VI-IV) complexes: cis-dioxomolybdenum(VI) complexes containing hydrogen-bond acceptors or donors.

The complexes cis-TpiPrMoVIO2(OAr-R) (TpiPr=hydrotris(3-isopropylpyrazol-1-yl)borate, -OAr-R=hydrogen-bonding phenolate derivative) are formed upon reaction of TpiPrMoO2Cl, HOAr-R, and NEt3 in dichloromethane. The orange, diamagnetic, dioxo-Mo(VI) complexes exhibit strong nu(MoO2) IR bands at ca. 935 and 900 cm(-1) and NMR spectra indicative of Cs symmetry. They undergo electrochemically reversible, one-electron reductions at potentials in the range -0.836 to -0.598 V vs SCE; the only exception is the 2-CO2Ph derivative, which exhibits an irreversible reduction at -0.924 V. The complexes display distorted octahedral geometries, with a cis arrangement of terminal oxo ligands and with d(Mo=O)av=1.695 A and angle(MoO2)av=103.2 degrees. The R groups of the 2-CHO and 2-NHCOMe derivatives are directed away from the oxo groups and into a cleft in the TpiPr ligand; these derivatives are characterized by Mo-O-Cipso angles of ca. 131 degrees (conformation 1). The R group(s) in the 2-CO2Me and 2,3-(OMe)2 derivatives lie above the face of the three O-donor atoms (directed away from the TpiPr ligand) and the complexes display Mo-O-Cipso angles of 153.1(2) and 149.7(2) degrees, respectively (conformation 2). Conformations 1 and 2 are both observed in the positionally disordered 2-COMe and 2-COEt derivatives, the two conformers having Mo-O-Cipso angles of 130-140 and >150 degrees, respectively. The 3-COMe and 3-NEt2 derivatives have substituents that project away from the TpiPr ligand and Mo-O-Cipso angles of 134.2(2) and 147.7(2) degrees, respectively. Many of the complexes exhibit fluxional behavior on the NMR time scale, consistent with the rapid interconversion of two conformers in solution.

Coupling of CpCr(CO)3 and heterocyclic dithiadiazolyl radicals. synthetic, x-ray diffraction, dynamic NMR, EPR, CV, and DFT studies.

The reaction of the 1,2,3,5-dithiadiazolyls (4-R-C(6)H(4)CN(2)S(2))(2) (R = Me, 2a; Cl, 2b; OMe, 2c; and CF3, 2d) and (3-NC-5-tBu-C(6)H(3)CN(2)S(2))(2) (2e) with [CpCr(CO)(3)](2) (Cp = eta(5)-C(5)H(5)) (1) at ambient temperature respectively yielded the complexes CpCr(CO)(2)(eta(2)-S(2)N(2)CC(6)H(4)R) (R = 4-Me, 3a; 4-Cl, 3b; 4-OMe, 3c; and 4-CF(3), 3d) and CpCr(CO)(2)(eta(2)-S(2)N(2)CC(6)H(3)-3-(CN)-5-(tBu)) (3e) in 35-72% yields. The complexes 3c and 3d were also synthesized via a salt metathesis method from the reaction of NaCpCr(CO)(3) (1B) and the 1,2,3,5-dithiadiazolium chlorides 4-R-C(60H(4)CN(2)S(2)Cl (R = OMe, 8c; CF(3), 8d) with much lower yields of 6 and 20%, respectively. The complexes were characterized spectroscopically and also by single-crystal X-ray diffraction analysis. Cyclic voltammetry experiments were conducted on 3a-e, EPR spectra were obtained of one-electron-reduced forms of 3a-e, and variable temperature 1H NMR studies were carried out on complex 3d. Hybrid DFT calculations were performed on the model system [CpCr(CO)(2)S(2)N(2)CH] and comparisons are made with the reported CpCr(CO)(2)(pi-allyl) complexes.

Heterocyclic thionates as a new class of bridging ligands in oxo-centered triangular cyclopentadienylchromium(III) complexes.

The interactions of the benzothiazolate complex, CpCr(CO)(2)(SCSN(C(6)H(4))) (2), and the tetrazole thiolate complex, CpCr(CO)(3)(eta(1)-SCN(4)Ph) (3), with controlled amounts of Me(3)OBF(4) and (MeO)(2)SO(2), respectively, produced the corresponding mu(3)-oxo trinuclear thionate-bridged complexes, [Cp(3)Cr(3)(mu(2)-OH)(mu(3)-O)(mu(2)-eta(2)-SCSN(C(6)H(4)))(2)](5)BF(4) (45%) and [Cp(3)Cr(3)(mu(2)-OH)(mu(3)-O)(mu(2)-eta(2)-SCN(4)Ph)(2)](9)(MeOSO(3)) (53%), together with their respective free dimethylated thiolate ligands, [MeSCSNMe(C(6)H(4))](4)BF(4) and (Me(2)SCN(4)Ph)(8)MeOSO(3). The reaction of 3 with Me(3)OBF(4) resulted in the isolation of a binuclear complex, [Cp(2)Cr(2)(mu-OH)(mu-eta(2)-SCN(4)Ph)(2)](7)BF(4) (43%), and (8)BF(4) (27%). The reaction of the thiopyridine complex, CpCr(CO)(2)(SPy) (4), with I(2) also produced a similar mu(3)-oxo complex 10 (31%), together with CpCrI(2)(THF) (11) and the disulfide (SPy)(2). Similar reactions with 2 and 3 and I(2) yielded species 5 and 7, together with 11 and disulfides derived from their respective ligands. Cyclic voltammograms recorded in solutions of 5 and 9 indicated that the compounds could be reduced and oxidized at very similar potentials. An EPR spectrum characteristic of a compound with axial symmetry was obtained for 9 at 7 K. Single-crystal X-ray diffraction analyses confirmed that species 7 is dinuclear, whereas 5 and 9 are structural trinuclear analogues, each containing a mu(3)-oxo central core.