Evaluation of Nanoparticles Covalently Bound with BODIPY for Their Photodynamic Therapy Applicability.

Photodynamic therapy (PDT) relies on the combined action of a photosensitizer (PS), light at an appropriate wavelength, and oxygen, to produce reactive oxygen species (ROS) that lead to cell death. However, this therapeutic modality presents some limitations, such as the poor water solubility of PSs and their limited selectivity. To overcome these problems, research has exploited nanoparticles (NPs). This project aimed to synthesize a PS, belonging to the BODIPY family, covalently link it to two NPs that differ in their lipophilic character, and then evaluate their photodynamic activity on SKOV3 and MCF7 tumor cell lines. Physicochemical analyses demonstrated that both NPs are suitable for PDT, as they are resistant to photobleaching and have good singlet oxygen (1O2) production. In vitro biological analyses showed that BODIPY has greater photodynamic activity in the free form than its NP-bounded counterpart, probably due to greater cellular uptake. To evaluate the main mechanisms involved in PDT-induced cell death, flow cytometric analyses were performed and showed that free BODIPY mainly induced necrosis, while once bound to NP, it seemed to prefer apoptosis. A scratch wound healing test indicated that all compounds partially inhibited cellular migration of SKOV3 cells.

Inherently Antimicrobial P(MMA-ran-DMAEMA) Copolymers Sensitive to Photodynamic Therapy: A Double Bactericidal Effect for Active Wound Dressing.

In this work, two compounds belonging to the BODIPY family, and previously investigated for their photosensitizing properties, have been bound to the amino-pendant groups of three random copolymers, with different amounts of methyl methacrylate (MMA) and 2-(dimethylamino)ethyl methacrylate (DMAEMA) in the backbone. The P(MMA-ran-DMAEMA) copolymers have inherently bactericidal activity, due to the amino groups of DMAEMA and to the quaternized nitrogens bounded to BODIPY. Systems consisting of filter paper discs coated with copolymers conjugated to BODIPY were tested on two model microorganisms, Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). On solid medium, irradiation with green light induced an antimicrobial effect, visible as a clear inhibition area around the coated disks. The system based on the copolymer with 43% DMAEMA and circa 0.70 wt/wt% of BODIPY was the most efficient in both bacterial species, and a selectivity for the Gram-positive model was observed, independently of the conjugated BODIPY. A residual antimicrobial activity was also observed after dark incubation, attributed to the inherently bactericidal properties of copolymers.

Meso- and Rac-[bis(3-phenyl-6-tert-butylinden-1-yl)dimethylsilyl]zirconium Dichloride: Precatalysts for the Production of Differentiated Polyethylene Products with Enhanced Properties.

Ansa-zirconocene complexes are widely employed as precatalysts for olefin polymerization. Their synthesis generally leads to mixtures of their rac and meso isomers, whose separation is often problematic. In this contribution, we report on the synthesis of a novel silyl-bridged bis(indenyl)-based metallocene, and on the separation of its rac and meso isomers by simple recrystallization from toluene. The two complexes, activated by methylaluminoxane (MAO), have been used as precatalysts in ethylene/1-hexene copolymerization. Regardless of the reaction conditions, the meso complex outperformed its rac congener. A similar trend was observed by performing the process in the presence of the silica-supported versions of the complexes. This is remarkable, since meso metallocenes generally display lower activities than their rac analogues. Furthermore, the meso isomer generates polymer products that are more in line with the targets for the preparation of a bimodal PE grade made of a lower-MW high-density (HDPE) fraction and a higher-MW linear low-density (LLDPE) fraction.

Scandium calix[n]arenes (n = 4, 6, 8): structural, cytotoxicity and ring opening polymerization studies.

Interaction of [Sc(OR)3] (R = iPr or triflate) with p-tert-butylcalix[n]arenes, where n = 4, 6, or 8, affords a number of intriguing structural motifs, which are relatively non-toxic (cytotoxicity evaluated against cell lines HCT116 and HT-29) and a number were capable of the ring opening polymerization (ROP) of cyclohexene oxide.

Comparative assessment of marine weathering of ROP-derived biopolymers against conventional plastics.

Bio-based plastics were designed to replace single-use plastics and to cause less post-consumer environmental damage. This paper assesses the weathering of four bio-based polymers created by ring opening polymerization (ROP) promoted by a previously reported Ti-based catalyst, to detect any problems before production was scaled up. Samples were aged in seawater to identify degradation products and monitor structural changes. Surfaces evidenced degradation and a range of leaching products was observed. Aside from compounds used in the preparation of the plastics (i.e. residual monomers and benzyl alcohol), the degradation products included carboxylic acids (often found in plastic leachate), oxacyclohexadecan-2-one (potentially toxic to aquatic life) and triphenylmethane (potential carcinogen). Overall, there were fewer structural changes in the fossil fuel based polymer (PS) and in the commercially available bio-based plastic studied for comparison purposes than the lab based bio-based polymers.

Lithium calix[4]arenes: structural studies and use in the ring opening polymerization of cyclic esters.

We have structurally characterized a number of lithiated calix[4]arenes, where the bridge in the calix[4]arene is thia (-S-, LSH4), sulfinyl (-SO-, LSOH4), sulfonyl (-SO2-, LSO2H4), dimethyleneoxa (-CH2OCH2-, LCOCH4) or methylene (-CH2-, LH4). In the case of L4SH4, interaction with LiOtBu led to the isolation of the complex [Li8(L4S)2(THF)4]·5THF (1·5THF), whilst similar interaction of L4SOH4 led to the isolation of [Li6(L4SOH)2(THF)2]·5(THF) (2·5THF). Interestingly, the mixed sulfinyl/sulfonyl complexes [Li8(calix[4]arene(SO)(SO2)(SO1.68)2)2(THF)6]·8(THF) (3·8THF) and [Li5Na(LSO/3SO2H)2(THF)5]·7.5(THF) (4·7.5(THF) have also been characterized. Interaction of LiOtBu with LSO2H4 and LCOCH4 afforded [Li5L4SO2(OH)(THF)4]·2THF (5·2THF) and [Li6(LCOC)2(HOtBu)2]·0.78THF·1.22hexane (6·0.78THF·1.22hexane), respectively. In the case of LH4, reaction with LiOtBu in THF afforded a monoclinic polymorph [LH2Li2(thf)(OH2)2]·3THF (7·3THF) of a known triclinic form of the complex, whilst reaction of the de-butylated analogue of LH4, namely de-BuLH4, afforded a polymeric chain structure {[Li5(de-BuL)(OH)(NCMe)3]·2MeCN} n (8·2MeCN). For comparative catalytic studies, the complex [Li6(LPr)2(H2O)2]·hexane (9 hexane), where LPr2H2 = 1,3-di-n-propyloxycalix[4]areneH2, was also prepared. The molecular crystal structures of 1-9 are reported, and their ability to act as catalysts for the ring opening (co-)/polymerization (ROP) of the cyclic esters ε-caprolactone, δ-valerolactone, and rac-lactide has been investigated. In most of the cases, complex 6 outperformed the other systems, allowing for higher conversions and/or greated polymer M n.

INSIGHTS into the structures adopted by titanocalix[6 and 8]arenes and their use in the ring opening polymerization of cyclic esters.

Interaction of p-tert-butylcalix[6]areneH6, L1H6, with [TiCl4] afforded the complex [Ti2Cl3(MeCN)2(OH2)(L1H)][Ti2Cl3(MeCN)3(L1H)]·4.5MeCN (1·4.5MeCN), in which two pseudo-octahedral titanium centres are bound to one calix[6]arene. A similar reaction but employing THF resulted in the THF ring-opened product [Ti4Cl2(µ3-O)2(NCMe)2(L)2(O(CH2)4Cl)2]·4MeCN (2·4MeCN), where LH4 = p-tert-butylcalix[4]areneH4. Interaction of L1H6 with [TiF4] (3 equiv.) led, after work-up, to the complex [(TiF)2(µ-F)L1H]2·6.5MeCN (3·6.5MeCN). Treatment of p-tert-butylcalix[8]areneH8, L2H8, with [TiCl4] led to the isolation of the complex [(TiCl)2(TiClNCMe)2(µ3-O)2(L2)]·1.5MeCN (4·1.5MeCN). From a similar reaction, a co-crystallized complex [Ti4O2Cl4(MeCN)2(L2)][Ti3Cl6(MeCN)5(OH2)(L2H2)]·H2O·11MeCN (5·H2O 11MeCN) was isolated. Extension of the L2H8 chemistry to [TiBr4] afforded, depending on the stoichiometry, the complexes [(TiBr)2(TiBrNCMe)2(µ3-O)2(L2)]·6MeCN (6·6MeCN) or [[Ti(NCMe)2Br]2[Ti(O)Br2(NCMe)](L2)]·7.5MeCN (7·7.5MeCN), whilst use of [TiF4] afforded complexes containing Ca2+ and Na+, thought to originate from drying agents, namely [Ti8CaF20(OH2)Na2(MeCN)4(L2)2]·14MeCN (8·14MeCN), [Na(MeCN)2][Ti8CaF20NaO16(L2)2]·7MeCN (9·7MeCN) or [Na]6[Ti8F20Na(MeCN)2(L2)][Ti8F20Na(MeCN)0.5(L2)]·15.5(C2H3N) (10·15.5MeCN). In the case of [TiI4], the ladder [(TiI)2(TiINCMe)2(µ3-O)2(L2)]·7.25CH2Cl2 (11·7.25CH2Cl2) was isolated. These complexes have been screened for their potential to act as catalysts in the ring opening polymerization (ROP) of ε-caprolactone (ε-CL), δ-valerolactone (δ-VL) and rac-lactide (r-LA), both in air and N2. For ε-CL and δ-VL, moderate activity at 130 °C over 24 h was observed for 1, 9 and 11; for r-LA, only 1 exhibited reasonable activity. In the case of the co-polymerization of ε-CL with δ-VL, the complexes 1 and 11 afforded reasonable conversions and low molecular weight polymers, whilst 4, 6, and 9 were less effective. None of the complexes proved to be active in the co-polymerization of ε-CL and r-LA under the conditions employed herein.

Synthesis and structures of mono- and di-nuclear aluminium and zinc complexes bearing α-diimine and related ligands, and their use in the ring opening polymerization of cyclic esters.

A series of organoaluminium imino-amido complexes of the type {[ArNC(Me2)C(Me)[double bond, length as m-dash]NAr]AlMe2} (Ar = 2,6-iPr2C6H3 (1), Ar = 2,6-Et2C6H3 (2); Ar = 2,6-Me2C6H3 (3) have been prepared via reaction of AlR3 and the respective α-diimine. Similar reaction of the bis(α-diimine) [ArN[double bond, length as m-dash]C(Me)C(Me)[double bond, length as m-dash]N-]2 (Ar = 2,6-iPr2C6H3) with AlMe3 afforded the bimetallic complex [ArN-C(Me)2C(Me)[double bond, length as m-dash]NAlMe2]2 (4), whilst reaction of the acetyl-imino compound [O[double bond, length as m-dash]C(Me)C(Me)[double bond, length as m-dash]NAr] (Ar = 2,6-Et2C6H3) with AlMe3 afforded the bimetallic complex {[OCMe2CH(Me)[double bond, length as m-dash]NAr]AlMe2}2 (5). In related organozinc chemistry, we have isolated {[ArNC(Me)(Et)C(Me)[double bond, length as m-dash]NAr]ZnEt} (Ar = 2,6-iPr2C6H3, 6) and the trinuclear complex {[ArN[double bond, length as m-dash]C(Me)COCHCO(Me)C(Me)[double bond, length as m-dash]NAr][OCH(Me)C(Me)[double bond, length as m-dash]NAr](ZnEt)3} (Ar = 2,6-iPr2C6H3, 7) from reactions of ZnEt2 with ArN[double bond, length as m-dash]C(Me)C(Me)[double bond, length as m-dash]NAr or [O[double bond, length as m-dash]C(Me)C(Me)[double bond, length as m-dash]NAr], respectively. Reaction of the bis(α-diimine), LiPr-N2-ArCH2Ar-N2, derived from 4,4'-methylenebis(2,6-diisopropylaniline), with ZnCl2 affords [LiPr-N2-ArCH2Ar-N2(ZnCl2)2] (8). The molecular structures of complexes 1-8 are reported. Preliminary results of the ability of 1-8, along with the previously reported metal-metal bonded complex {[ArN[double bond, length as m-dash]C(Me)C(Me)[double bond, length as m-dash]NAr]Al(THF)}2 (9), to act as catalysts for the ring opening polymerization (ROP) of the cyclic esters ε-caprolactone (ε-CL), δ-valerolactone (δ-VL) and rac-lactide (r-LA) are presented. For ε-CL and δ-VL, best results were obtained using the metal-metal bonded complex 9. For r-LA, the Al-based systems exhibited moderate activity affording only liquid oligomers, whilst the Zn-based systems performed better affording at 80 °C isotactic PLA with Mnca. 10 kDa with conversions of up to 66%. The co-polymerization of ε-CL with δ-VL was also examined, and differing preferences were noted for monomer incorporation.

Generalization of the Copper to Late-Transition-Metal Transmetallation to Carbenes beyond N-Heterocyclic Carbenes.

Carbene transition-metal complexes have become a prevalent family of catalysts enabling numerous organic transformations. Their facile synthetic access is a matter of great importance. To this end, the Cu(I) -NHC transfer methodology has emerged as a powerful alternative presenting attractive advantages over other methods. Herein, we report the remarkable ability of copper to transfer not only NHCs but also other types of carbenes such as abnormal NHCs (aNHCs), cyclic (alkyl)(amino)carbenes (CAACs), and mesoionic carbenes (MICs) to various transition metal precursors.

Homoleptic and heteroleptic bis-NHC Cu(I) complexes as carbene transfer reagents.

Homo- and heteroleptic bis-NHC copper(I) complexes have been efficiently used as carbene transfer reagents to Au and Pd. The simple and straightforward procedure allows for the synthesis of well-known gold complexes as well as novel cationic bis-NHC Pd(II) species.

N-heterocyclic carbene copper(I) catalysed N-methylation of amines using CO2.

The N-methylation of amines using CO2 and PhSiH3 as source of CH3 was efficiently performed using a N-heterocyclic carbene copper(i) complex. The methodology was found compatible with aromatic and aliphatic primary and secondary amines. Synthetic and computational studies have been carried out to support the proposed reaction mechanism for this transformation.

A general synthetic route to [Cu(X)(NHC)] (NHC = N-heterocyclic carbene, X = Cl, Br, I) complexes.

A one-pot procedure for the synthesis of [Cu(X)(NHC)] (X = Cl, Br, I) is reported. The reaction is applicable to a wide range of saturated and unsaturated NHC ligands, is scalable and proceeds under mild conditions using technical grade solvents in air.