Dendritic cell internalization of foam-structured fluorescent mesoporous silica nanoparticles

In this paper, foam-structured fluorescent mesoporous silica nanoparticles (FMSNs) are produced in a sol-gel method with the introduction of a phosphonate functional group. It is found that the phosphonate functionalized FMSNs with the foam structure minimizes the aggregation of FMSNs in solution. The average particle size of the FMSNs without and with phosphonate functionalization is 46.3 ± 5 nm and 60.5 ± 8 nm in diameter, respectively. The latter one exhibits higher fluorophore loading capacity (~67 ± 2.5%). The excitation wavelength (λ(ex)) of FMSNs is observed at 526 nm, approximate 12 nm larger in the Stoke-shift compared to the free organic dye at 494/514 nm. Furthermore, the photostability of the hydrophobic fluorophore is greatly improved by the FMSNs with the foam structure. In addition, the dose-dependent nature of FMSN uptake is assessed for the immune cells, the bone marrow-derived dendritic immune cells (BMDCs). Our results indicate that approximately 42% of BMDCs are able to take up foam-structured FMSNs (>5 μg/ml) without decreasing the viability of BMDCs. Thus, the phosphonate functionalized FMSNs with the foam structure are suitable to be used for many biomedical applications, especially in cell tracking.     

Solitaire and gemini metallocene porphyrazines.

We report the synthesis and physical characterization of a series of peripherally functionalized porphyrazines (pzs) of the forms H2[pz(A;B3)] and trans-H2[pz(A2);B2], where A is a dithiolene chelate of molybdocene or vanadocene and B is a solublizing group. The precursor pz's 8 and 9, of the form H2[pz(A;B3)], where A = (4-(butyloxycarbonyl)-S-benzyl)2 and B = di-tert-butylphenyl (8) or di-n-propyl (9), have been prepared, deprotected, and peripherally metalated with molybdocene and vanadocene to form 1(Mo(IV)) and 1(V(IV)), prepared from 8, and 2(Mo(IV)) from 9, respectively. Likewise, the protected trans-H2[pz(A2);B2)], where A = (S-benzyl)2 and B = 3,6-butyloxybenzene (12) or A = (S-benzyl)2 and B = (tert-butylphenyl)2 (13), have been prepared and peripherally metalated with molybdocene and vanadocene to give the trans dinuclear complexes, 3(Mo(IV),Mo(IV)), 3(V(IV),V(IV)) (from 12), and 4(V(IV),V(IV)) (from 13). A crystal structure of the trans vanadocene pz 4(V(IV),V(IV)) is presented; the distance between the two vanadium atoms is 14.5 A. The molybdocene-appended pz's are highly redox active and exhibit cyclic voltammograms that are more than just the sum of the metallocene and the parent pz's. Chemical oxidation with FcPF6 gives the Mo(V) species 1(Mo(V)), 2(Mo(V)), 3(Mo(V),Mo(IV)), and 3(Mo(V),Mo(V)). Their EPR spectra are indicative of extensive delocalization from the Mo(V) into the dithiolato-pz. The EPR spectrum of the mononuclear paramagnetic vanadocene pz, 1(V(IV)), shows an expected 8-line pattern for an S = 2 system with hyperfine coupling to a single 51V (I = 7/2) nucleus, but the dinuclear vanadocene pz's, 3(V(IV),V(IV)) and 4(V(IV),V(IV)), exhibit a striking 15-line pattern of the same breadth from the S = 1 state formed by exchange coupling between the S = 2 vanadium centers of a dinuclear complex. Thus, the porphyrazine macrocycle is capable of mediating magnetic exchange interactions between metal ions bound to the periphery, separated by 14.5 A.     

Tuning the singlet oxygen quantum yield of near-IR-absorbing porphyrazines

We report the quantum yields for singlet oxygen production by a series of porphyrazines (pz) of the form M[pz(An;B4-n)] (Scheme 1), where the peripheral substituent A is [S-R]2 with R = (CH2CH2O)3H, B is a fused alpha,alpha'-dialkoxybenzo group and M = 2H, Mg or Zn. These compounds show intense near-IR absorbance/emission (longest wavelength emission, approximately 830 nm). Their solubilities vary with R, whereas their optical properties do not. We show that singlet oxygen sensitization by these luminescent compounds can be "tuned" from essentially off to on by varying n and selection among M = 2H, Mg or Zn. The quantum yields vary ca 60-fold within the set of compounds studied, from phidelta = 0.007 for compound 3 to phidelta = approximately 0.4 for compound 11.     

Novel peripherally functionalized seco-porphyrazines: synthesis, characterization and spectroscopic evaluation

Co-macrocyclizations of 2,3-dipropylmaleonitrile and 2,3-di-(4-(methoxycarbonyl)phenyl)maleonitrile, respectively, with N,N′-dibenzyl-N,N′-di-(11-tetrahydropyranyloxy-3,6,9-trioxo-undecyl))maleonitrile and N,N,N′,N′-tetramethylmaleonitrile were used to prepare derivatives of the 4,5-diamino-porphyrazine systems including the zinc(II) complexes. Subsequent oxidation of the macrocycles with potassium permanganate gave the corresponding seco-porphyrazines. These were shown to be efficient sensitizers for the production of singlet oxygen (Φ_Δ=0.15-0.57) by the determination of their photophysical properties.     

ITQ-12: a new microporous silica polymorph potentially useful for light hydrocarbon separations

The new synthetic form of microporous crystalline silica, denoted as ITQ-12, shows a high potential for the separation of propane and propene from its mixtures.     

Synthesis and anticonvulsant activity of 3H-imidazo[4,5-c]-pyridazine, 1H-imidazo[4,5-d]pyridazine and 1H-benzimidazole analogues of 9-(2-fluorobenzyl)-6-methylamino-9H-purine

The 3H-imidazo[4,5-c]pyridazine, 1H-imidazo[4,5-d]pyridazine, and 1H-benzimidazole analogues of the potent anticonvulsant purine 9-(2-fluorobenzyl)-6-methylamino-9H-purine (1, 78U79) were synthesized and tested for anticonvulsant activity. The 3H-imidazo[4,5-c]pyridazines 8 and 9 were prepared in five stages from 3,4,5-trichloropyridazine (2) . The 1H-imidazolo[4,5-d]pyridazine 15 was synthesized in four stages from 5-[(benzyloxy)methyl]-1,5-dihydro-4H-imidazo[4,5-d] pyridazin-4-one (10a) . The benz-imidazole analogues 18 and 20 were prepared from 2,6-dinitroaniline in three stages. These compounds were one-tenth or less as active as 1 in protecting rats against maximal electroshock-induced seizures.     

Generation and Trapping of Acyl Nitrile Oxides from Substituted Aryl 1,3 Diketones in a Nitrating Mixture

Acyl nitrile oxides are readily generated and trapped in a nitrating mixture with N-methylmaleimide.     

At-line bioprocess monitoring by immunoassay with rotationally controlled serial siphoning and integrated supercritical angle fluorescence optics

In this paper we report a centrifugal microfluidic “lab-on-a-disc” system for at-line monitoring of human immunoglobulin G (hIgG) in a typical bioprocess environment. The novelty of this device is the combination of a heterogeneous sandwich immunoassay on a serial siphon-enabled microfluidic disc with automated sequential reagent delivery and surface-confined supercritical angle fluorescence (SAF)-based detection. The device, which is compact, easy-to-use and inexpensive, enables rapid detection of hIgG from a bioprocess sample. This was achieved with, an injection moulded SAF lens that was functionalized with aminopropyltriethoxysilane (APTES) using plasma enhanced chemical vapour deposition (PECVD) for the immobilization of protein A, and a hybrid integration with a microfluidic disc substrate. Advanced flow control, including the time-sequenced release of on-board liquid reagents, was implemented by serial siphoning with ancillary capillary stops. The concentration of surfactant in each assay reagent was optimized to ensure proper functioning of the siphon-based flow control. The entire automated microfluidic assay process is completed in less than 30 min. The developed prototype system was used to accurately measure industrial bioprocess samples that contained 10 mg mL⁻¹ of hIgG.