Academic literature on the topic 'Imido complexes form'

The tetradentate, partially flattened cone tungsten(VI) imido-calix[4]arene derivative [W(NC6H5)(t-BucalixH)]+Cl–, (4), is formed in good yield from reaction of p-tert-butyl-calix[4]arene (t-BucalixH4), and W(NC6H5)Cl4. A reaction mechanism involving a putative, bidentate calixarene intermediate W(NC6H5)(t-BucalixH2)Cl2 (3), which partitions by reversible cleavage of the imido group to give the known tetradentate calixarene complex W(t-Bucalix)Cl2 (2), and elimination of HCl to form the thermodynamic imido product 4 is proposed. A series of iso structural [W(NAr)(t-BucalixH)]+Cl– (Ar = C6H5 or o,m,p-C6H4CH3) imido derivatives (4–7), which adopt a partially flattened cone conformation in solution has been prepared by reaction of dichloride 2 with H2NAr (Ar = C6H5, o,m,p-C6H4CH3). Reaction of W(t-Bucalix)Cl2 with aliphatic amines affords a red product formulated as the nitrido complex, 9, which results from facile cleavage of the imido C—N bond.Key words: calix[4]arene complex, imido complex, nitrido complex, C—N bond cleavage, conformation, metallocalixarene.

A metathesis reaction of a WW bond and an NN bond was observed by reacting a W–W triply-bonded W(iii)₂ complex, (^tBuO)₃WW(O^tBu)₃ (1), with benzo[c]cinnoline derivatives to form biphenyl-linked dinuclear (imido)tungsten complexes 2–4.

The reaction of [Mo(η-C5Me5)Cl4] with the ortho-, meta-, or para-iodo-functionalized anilines 2-IC6H4NH2, 3-IC6H4NH2, 4-IC6H4NH2 yields imido or amine products of the type [Mo(η-C5Me5)Cl2(IC6H4N)] (2-I, 1, 3-I, 3, 4-I, 5) or [Mo(η-C5Me5)Cl4(IC6H4NH2)] (3-I, 2, 4-I, 4), respectively, depending on the reaction stoichiometry/conditions; we were unable to isolate an amine complex of the 2-I derivative. The reaction of [Mo(η-C5Me5)Cl4] with one equivalent of 2-I,4-FC6H3NH2 in the presence of Et3N afforded [Mo(η-C5Me5)Cl2(2-I,4-FC6H3N)]·MeCN (6·MeCN), which, upon exposure to air, afforded the Mo(VI) imido complex [Mo(η-C5Me5)Cl3(2-I,4-FC6H3N)] (7). For comparative studies, the structure of the aniline (C6H5NH2)-derived complex [Mo(η-C5Me5)Cl2(2-C6H3N)] (8) has also been prepared. The molecular structures of 1–8 have been determined and reveal packing in the form of zig-zag chains or ladders. The complexes catalyze, in the presence of benzyl alcohol under N2, the ring-opening polymerization (ROP) of ε-caprolactone affording relatively low molecular weight products. The MALDI-ToF spectra indicate that a number of polymer series bearing a variety of end groups are formed. Conducting the ROPs as melts or under air results in the isolation of higher molecular weight products, again bearing a variety of end groups. Kinetic studies reveal the aniline-derived imido complex 8 performs best, whilst a meta-iodo substituent and a Mo(V) centre are also found to be beneficial. The structures of the side products 2-IC6H4NH3Cl and 3-IC6H4NH3Cl are also reported.

The template reaction of a warm methanolic solution of Ni(OAc)2?4H2O S-n-propylisothiosemicarbazide hydroiodide and acetylacetone yielded the needle- like, brown, diamagnetic complex [Ni(L-H)]I?MeOH, and in the presence of an excess of NH 4NCS, brown, prismatic crystals of the complex [Ni(L-H)]NCS (1), both compounds involving the monoanionic form of the ligand, acetylacetone bis(S-n-propylisothiosemicarbazone), L. Slow recrystallization fromMeOH, EtOH, iPrOH and Me2CO gave the corresponding monosolvent complexes [Ni(L-H)]I?solvent, of which only those involving EtOH and iPrOH were suitable for structural analysis. The crystallographic parameters of [Ni(L-H)]I?EtOH (2) and [Ni(L-H)]I?iPrOH (3) are very similar to each other, showing their structures are isomorphic. The crystal structures of the title compounds consist of the independent ions: NCS-, or I-, and the chemically identical cation [Ni(L-H)]+, where L-H is the monoanion resulting from deprotonation of the acetylacetone moiety, a tetradentate N4 ligand forming a square-planar coordination around a Ni(II) ion. It was found that the isothiosemicarbazide fragment of the ligand has an imido form. The complex cations of the compounds [Ni(L-H)]NCS and [Ni(L-H)]I?EtOH exhibit significant difference only in the conformation of their propyl groups.

Chalcogenide chemistry is rich and diverse: The large variety of molecular sulfur and selenium compounds can be ascribed to their multiple stable oxidation states and large radius enabling high coordination. Sulfur-nitrogen chemistry is thoroughly explored and well-understood; polyimido sulfur species S(NR)n with charge m- (n = 2, 3, 4; m = 0, 2) are analogues of SOn molecules (with charge: m-) in which oxygen has been replaced by isovalent NR imido groups [1]. These compounds have been studied in depth and have been demonstrated to be versatile ligand systems which form multifaceted potentially catalytic metal complexes and compounds with lithium organics [2]. Selenium-nitrogen chemistry is comparatively less developed than sulfur-nitrogen chemistry despite of significant contributions to the field [3]. This may be ascribed to the rich redox chemistry of selenium in addition to its ability to polymerize, unfortunately none of these properties are easily controlled. A crucial parameter in the development of sulfur-nitrogen chemistry is attributed to the access to sulfur diimides S(NR)2 and sulfur triimides S(NR)3. Therefore, our starting point in exploring new directions of selenium-nitrogen chemistry was to revisit Se(NtBu)2 (tBu = tertbutyl), which has been used as ligand for metal complexes, but also discussed in large detail with respect to structural geometry and stability. Herein, we are presenting a study of selenium-nitrogen chemistry based on Se(NtBu)2.

The activity that replicates yeast DNA in vitro can be isolated from cells of the budding yeast Saccharomyces in a high-Mr (approximately 2 × 10(6] form. Several lines of evidence indicate that this fraction contains a multiprotein replicative complex. A functional assay has been developed for the analysis of the interaction of the replicating activity with DNA. Binding of the activity required Mg2+, but did not require the addition of ATP or the other ribo- or deoxynucleoside triphosphates. However, the ATP analogues adenosine 5′-[gamma-thio]triphosphate and adenosine 5′-[beta gamma-imido]triphosphate blocked the binding, suggesting that ATP participates in the interaction at some stage. The binding was template (origin)-specific in either the presence or the absence of ATP and the other nucleoside triphosphates; however, ATP stabilized the replicating activity. The preferential inhibition of binding that was observed in the presence of the DNA topoisomerase II inhibitor coumermycin suggests that the requirement for ATP may be at least partially accounted for by the involvement of this enzyme in the initial interaction of the replicating activity with DNA. Finally, the binding was rapid. In contrast, DNA synthesis displayed a lag when assayed directly without first allowing a period for the replicating activity to bind to the DNA. In addition, binding was ‘tight’, as judged by the resistance of the protein–DNA complexes to salt in comparison with the relative sensitivity of binding. The replicating activity was not readily displaced from the complexes by exogenous DNAs, either possessing or lacking yeast origins of replication. The results suggest that the interaction of the replicating activity with the DNA occurs in more than one stage.

El subministrament d'energia sostenible és un desafiament crític que enfronta la humanitat. La dependència dels combustibles fòssils ha despertat l'interès en el desenvolupament de fonts d'energia lliures de carboni, entre les quals el dihidrogen que té una alta densitat d'energia seria un dels més prometedors sempre que es generi a partir d'alternatives renovables. En aquest context, dissociar l'aigua per produir hidrogen com a combustible és de gran interès i, per tant, s'estan desenvolupant una gran quantitat de catalitzadors per accelerar la velocitat d'aquesta reacció, preferiblement obtinguts a partir de metalls de transició abundants. Amb l'objectiu d'optimitzar l'economia de l'àtom de metall i facilitar l'anàlisi mecanístic, els complexos moleculars són una bona opció com a catalitzadors homogenis. En aquest tipus de compostos, els centres metal·lics que generalment es requereixen poden accedir a múltiples estats d'oxidació, de vegades a través d'intermedis de tipus metall-hidrur. No obstant això, el disseny de catalitzadors per a la reacció d'evolució de l'hidrogen (HER) inclou també una família de complexos amb lligands no innocents que poden operar com un reservori d'electrons i / o un lloc de protonació. El primer capítol d'aquesta tesi doctoral introdueix la necessitat i les tècniques per a la producció d'hidrogen per recolzar la demanda d'energia, incloent els electrocatalitzadors per HER basats en els metalls no nobles, níquel i cobalt. El segon capítol descriu els objectius d'aquesta Tesi, és a dir, la síntesi i caracterització dels lligands basats en diiminpiridina (PDI), actius en redox, juntament amb els complexos de níquel i cobalt obtingut a partir d'aquests lligands. Es presenten també com a objectius la seva avaluació electrocatalítica en HER així com la descripció dels processos des del punt de vista mecanístic. El tercer capítol presenta la preparació d'un conjunt de lligands PDI pentadentats, juntament amb la síntesi i caracterització completa de complexos de Ni(II) de hexacoordinats [Ni(Ph2PPrPDI)(Cl)](Cl) (1(Cl)) i [Ni(Ph2PPrPDI)(p)Cl)(Cl)](Cl) (2(Cl)). La ubicació dels electrons després de la reducció electroquímica d'1(Cl) es va examinar mitjançant càlculs de la teoria del funcional de la densitat (DFT) juntament amb la ressonància paramagnètica electrònica (EPR), la qual cosa va mostrar que la primera reducció d'un electró es produeix en el metall i la segona en el lligand. Es van estudiar també les propietats redox i catalítiques d'ambdós complexos. D'una banda, es va observar un potencial redox més positiu i, per tant, un sobrepotencial més baix per a 2(Cl), el que indica que la presència del substituent electroatraient Cl al lligand PDI millora l'activitat electrocatalítica. D'altra banda, 1(Cl) és més actiu per al HER en termes de TOF i constant de velocitat. Els estudis d'estabilitat a curt termini per a 1(Cl) i 2(Cl) en condicions de HER per CV indiquen que la catàlisi és homogènia sense descomposició, mentre que l'estabilitat a llarg termini analitzada per electròlisi potencial controlada mostra la generació d'una nova espècie transitòria que pot desencadenar la reacció d'oxidació d'hidrogen i al seu torn reduir el sobrepotencial per a la HER. El quart capítol s'enfoca en la síntesi i caracterització de complexos de Co coordinats de cinc amb els lligands aplicats en el tercer capítol ([CoI(Ph2PPrPDI](BF4), 3(BF4) i [CoI(Ph2PPrPDI(p)Cl](BF4), 4(BF4)). Les dades de l'electroquímica mostren que aquests complexos són actius per a la HER en medi orgànic, passant després de la reacció amb protons per espècies d'hidrur de Co(III) que es van identificar mitjançant espectroscòpia UV-vis i RMN. Sobre la base de l'espectroscòpia RMN, el compost de Co(I) inicial es va recuperar després d'un cicle de reacció catalític, el que demostra un mecanisme homolític per HER. Finalment, el cinquè capítol enumera les conclusions més rellevants extretes del treball realitzat.
Sustainable energy supply is a critical challenge humanity is facing. The dependence of fossil fuels have ignited interest in the development of carbon-free energy sources, among which energy-dense dihydrogen would be one of the most promising when generated from renewable alternatives. In this context, splitting water to produce hydrogen as fuel is of great interest, and hence a large number of catalysts made from earth-abundant transition metals have been developed to accelerate the reaction rate. For the purpose of effectively using metal-atom economy and facilitating mechanistic analysis, molecular complexes as homogenous catalysts got much attention. In this kind of compounds, metal centres are usually required to accommodate multiple redox states and experience metal-hydride intermediates. However, there has been a renaissance in catalysts’ design for the hydrogen evolution reaction (HER) by coordinating the metal centre with non-innocent ligands who can operate as an electron reservoir or/and protonation site. The first Chapter of this PhD Thesis generally introduce the need and techniques for hydrogen production to support the energy demand, reviewing electrocatalysts for the HER based on the non-noble metals nickel and cobalt. The second Chapter describes the objectives of this Thesis, i.e., the synthesis and characterization of redox-active pyridine diimine (PDI)-based ligands and the corresponding nickel and cobalt complexes. Their electrocatalytic evaluation in HER is aimed, as well as the description of the processes from the mechanistic point of view. The third Chapter presents the preparation of a set of pentadentate PDI ligands, synthesis and full characterization of six-coordinated Ni(II) complexes [Ni(Ph2PPrPDI)(Cl)](Cl) (1(Cl)) and [Ni(Ph2PPrPDI(p)Cl)(Cl)](Cl) (2(Cl)) using techniques including mass spectroscopy, UV-vis spectroscopy, X-ray crystallography and elemental (C, H, N) analysis. The electron location upon electrochemical reduction of 1(Cl) was examined by density functional theory (DFT) calculations along with electron paramagnetic resonance (EPR), revealing the metal-based nature for the first one-electron reduction and ligand-based for the second one. The redox and catalytic properties of both complexes were studied. On the one hand, more positive redox potential and therefore lower overpotential were observed for 2(Cl), indicating that the presence of the electron-withdrawing Cl substituent in the PDI ligand scaffold improves the electrocatalytic activity. On the other hand, 1(Cl) is more active for the HER in terms of turnover frequency and rate constant. Short-term stability studies for 1(Cl) and 2(Cl) in the course of HER by CV indicates homogenous catalysis without decomposition, whereas long-term stability analysed by controlled potential electrolysis shows the generation of a new transitory species which can trigger the hydrogen oxidation reaction and reduce the overpotential for the HER. The fourth Chapter focus on the synthesis and characterization of five-coordinated Co complexes bearing the ligands applied in the third Chapter ([CoI(Ph2PPrPDI](BF4), 3(BF4) and [CoI(Ph2PPrPDI(p)Cl](BF4), 4(BF4)). Electrochemistry data shows that these complexes are active for the HER in organic media, undergoing protonation to form Co(III) hydride species which were identified by UV-vis and NMR spectroscopy. On the basis of NMR spectroscopy, the initial Co(I) compound was recovered after a catalytic reaction cycle, demonstrating a homolytic mechanism for HER by this system. Finally, the fifth Chapter lists the most relevant conclusions extracted from the work carried out.

Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 1999.
Includes bibliographical references (leaves 172-179).
Chapter 1. The synthesis and resolution of sterically encumbered biphenols is presented. -- Chapter 2. The synthesis of molybdenum(VI) imido alkylidene complexes containing racemic and optically pure biphenoxides (Biphen and Biad) is reported. -- Chapter 3. The 1H NMR spectroscopic data for molybdenum(VI) imido alkylidene biphenoxide complexes prepared in Chapter 2 are presented. -- Chapter 4. The application of catalysts prepared in Chapter 2 in asymmetric ring-closing metathesis (ARCM) is described. -- Chapter 5. Synthesis, characterization and reactivity of (±)(Me2)W(Neo) and (±)(iPr 2)W(Neo) . PMe2Ph is discussed.
by John Bryson Alexander.
Ph.D.

This thesis describes the development of new catalytic systems based upon iron complexes and their reactivity toward ethylene. First, we focused our interest on the synthesis of iron(III) precursors chelated by monoanionic ligand. Those complexes were obtained either by reaction of the monoanionic ligand with FeCl3 or through oxidation of the iron(II) complex. The second reaction led to binuclear complexes. Then, another aim of the thesis was to design new well-defined cocatalysts for the activation of iron complexes. The study of the reaction between an alcohol and the trimethylaluminum allowed us to reach this aim. Aluminum complexes adopted either a binuclear framework or a trinuclear one, depending on the nature of alcohol reagent. Besides this work, new iron(II) and nickel(II) complexes chelated by imino-imidazole ligands bearing a pendant donor function L were synthesized. All complexes have been evaluated for the oligomerization of ethylene in the presence of EtAlCl2 or MAO as cocatalyst. Only nickel complexes were active toward ethylene transformation.

碩士
中興大學
化學系所
95
Synthetic and structural studies of Pd(II) and Ag(I) complexes of iminoyl-substituted N-heterocyclic carbine ligands. Reaction of 2a-c with Ag2O leads to the silver carbene complexes (C–N)AgBr (3a-c). Carbene transfer from Ag to Pd occurs when compounds 3a-c are treated with PdCl2 to yield bis(carbene) complexes (C–N)2PdCl2 (4a-c). The molecular structures of the complexes 3c and 4b have been determined by X-ray diffraction studies, which revealed the palladium complex 4b had a trans square-planar geometry at their respective metal centers. In a trans coordination geometry, the two carbene ligands can have their two N(imidazole) substituents oriented in the same or in the opposite directions with respect to the coordination plane, denoted syn and anti for 4a-c. The in situ Pd(OAc)2-2a-c and complexes 4a-c were found to be active catalysts for the Heck and Suzuki C-C coupling reactions, the less reactive aryl chloride substrates can also be used.

碩士
中原大學
化學研究所
101
Four imino-benzotriazole phenoxide ligands, C1DMeIBTP-H (A), C1DIPIBTP-H (B), C1PhIBTP-H (C) and C1BnIBTP-H (D) were prepared in good yield(≧70%) from the condensation of 3-(2H-benzotriazol-2-yl)-2-hydroxy- 5-methyl benzaldehyde (C1AldBTP-H) with benzylamine or arylamine (aniline, 2,6-dimethylaniline and 2,6-diisopropylaniline (1.1 equiv.)) in solvent (toluene or ether). Zinc catalysts supported by imino-benzotriazole phenoxide ligands were characterized by microanalyses as well as single-crystal X-ray structural determinations. Treatment of the ligand (C1DMeIBTP-H or C1DIPIBTP-H) with 1.0 mol equiv. of ZnEt2 in toluene under the same stoichiometric proportion afforded the dimeric zinc complexes ([(-C1DMeIBTP)ZnEt]2 (1); [(-C1DIPIBTP)ZnEt]2 (2)) in 50% and 53% yields, respectively. The reaction of diethyl zinc (ZnEt2) with C1PhIBTP-H or C1BnIBTP-H (2.0 equiv.) yields tetra-coordinated monomeric zinc complex [(C1PhIBTP)2Zn] (3) or [(C1BnIBTP)2Zn] (4). Catalysis for ring-opening polymerization (ROP) of -caprolactone (-CL), -butyrolactone (-BL), and L-lactide (L-LA) of complexes 1-2 are investigated. Zinc complexes 1 and 2 catalyze the ring-opening polymerization of -caprolactone (-CL) in the presence of 9-anthracenemethanol (9-AnOH) with efficient catalytic activities in a controlled fashion. Additionally, polymerizations of -butyrolactone (-BL) catalyzed by complex 1 and 2 are demonstrated in a “living” character with the expected molecular weights and narrow molecular weight distributions. To examine stereoselectivity of PHB, complex 1 and 2 were employed as catalysts toward ROP of -BL. Experimental results exhibit that complex 1 or complex 2 catalyzes -BL to produce atactic PHB (Pr = 0.48). Furthermore, complex 1 catalyzes rac-LA to yield heterotactic PLA (Pr = 0.66). We also investigate the reaction rate of ring-opening polymerization by complex 1 in the presence of 9-AnOH catalyzes -CL, -BL, and L-LA. In addition, complex 3 and complex 4 are demonstrated to catalyze the ROP of L-LA in the presence of 9-AnOH. However, the catalytic activity and reaction time of complex 3 are much better than complex 4.

碩士
中原大學
化學研究所
102
Four novel sulfonate phenol ligands, HBBTP(OS)-H (A), CH3BBTP(OS)-H (B), OMeBBTP(OS)-H (C) and CF3BBTP(OS)-H (D), have been prepared by the sulfonylation ) with one molar equiv of the corresponding 4-substituted benzenesulfonyl chloride in the presence of excess triethylamine. Zinc (Zn) complexes supported by sulfonate phenoxide ligands have been synthesized and characterized by microanalyses. The reaction of diethyl zinc (ZnEt2) with one equivalent amount of RBBTP(OS)-H (R=H, CH3, OMe and CF3) produces the monomeric zinc complex [HBBTP(OS)ZnEt] (A), [CH3BBTP(OS)ZnEt] (B), [OMeBBTP(OS)ZnEt] (C) and [CF3BBTP(OS)ZnEt] (D). Catalysis for ring-opening polymerization (ROP) of -caprolactone (-CL), -butyrolactone (-BL) and L-Lactide (L-LA) of complexes (2)-(4) are investigates. Zinc complexes (2)-(4) catalyze the ring-opening polymerization of -CL in the presence of 9-anthracenemethanol (9-AnOH) with efficient catalytic activities in a controlled fashion. In -CL polymerization, the activity of complex (4) is higher than that of complex(3) and (2), which is probably due to the higher Lewis acidity of Zn2+ metal caused by electron-withdrawing substitute, trifluoromethyl(-CF3) on the 4-position of the benzenesulfonate group. Additionally, polymerization of -BL and L-LA catalyzed by complex (4) is demonstrated in a“living”and“immortal”character with the expected molecular weights and narrow molecular weight distributions. To examine stereoselectivity of PLA, complex (4) was employed as catalysts toward ROP of rac-LA. Experimental results exhibit that complex (4) catalyzes rac-LA to produce atactic PLA (Pr = 0.50). Furthermore, complex (4) catalyzes -BL to yield atactic PHB (Pr = 0.46). We also investigate the reaction rate of ring-opening polymerization by complex (4) in the presenceof 9-AnOH catalyzes -CL, -BL and L-LA. 　　Three imino-benzotriazole phenoxide ligand, C1NNIBTP-H (E), C1PPIBTP-H (F), C1PrIBTP-H (G), C1FuIBTP-H (H), C1NOIBTP-H (I) have been prepared in good yield(≧70%) from the condensation of 3-(2H-benzotriazol-2-yl)-2-hydroxy-5-methyl benzaldehyde (C1AldBTP-H) with N, N-dimethylethylenediamine, N-(2-Aminoethyl)piperidine, 2-(Aminomethyl)pyridine, Furfurylamine and 2-Methoxyethylamine (1.1 equiv.) inether solvent. Titanium catalysts supported by imino-benzotriazole phenoxide ligands were characterized by microanalyses as well assingle-crystal X-ray structural determinations. The reaction of Titanium isopropoxide (Ti(OiPr)4) with C1NNIBTP-H yields six-coordinated monomeric titanium complex [(C1NNIBTP)Ti(OiPr)3] (5). Catalysis for ROP of -CL, -BL and L-LA of complex (5) is investigated. Titanium complex (5) catalyze the ROP of -CL in the presence of isopropanol (IPA) with efficient catalytic activities in a controlled manner. Additionally, polymerizations of L-LA catalyzed by complex (5) is demonstrated in a“living”and“immortal”character with the expected molecular weights and narrow polydispersity indexes (PDIs). To examine stereoselectivity of PLA, complex (5) was employed as catalysts toward ROP of rac-LA. Experimental results exhibit that complex (5) catalyzes rac-LA to produce atactic PLA (Pr = 0.50). We also investigate the reaction rate of ring-opening polymerization by complex (5) in the presenceof IPA catalyzes -CL, -BL and L-LA. 　　The reaction of Titanium isopropoxide (Ti(OiPr)4) with C1FuIBTP-H, C1NOIBTP-H yields six-coordinated dinuclear titanium complex [(C1FuIBTP)2Ti(OiPr)2] (6) and [(C1NOIBTP)2Ti(OiPr)2] (7). Complexes (6)-(7) were characterized by 1H and 13C NMR spectroscopy, elemental analyses determinations. Titanium complex (5) catalyze the ROP of -CL and L-LA in the presence of isopropanol (IPA) with optimal conditions. Each of complex (6)-(7) catalyze the ROP of -CL and L-LA. In -CL and L-LA polymerization, the activity of complex (5) is higher than that of complex (6) and (7).

AbstractEven after a decade of use, CAR-T cell therapy for non-Hodgkin lymphoma (NHL) is still evolving, and disease control is now the main concern in the majority of experienced centres. Indeed, despite highly appealing objective response (OR) rates in refractory patients, the long-term overall survival (OS) of this population has only slightly improved. Pivotal studies have suggested that 2-year OS rates do not surpass 30%, even though results improve when complete response (CR) is achieved within the first 3 months after treatment (Wang et al. 2020; Schuster et al. 2019; Neelapu et al. 2017). Although achieving this exceptionally high level of OR is praiseworthy, similar improvements have not been made regarding OS, and current OS probabilities are not satisfactory. Of course, there are multiple reasons for this; a substantial proportion of patients either do not achieve an initial response or experience progression very soon after treatment, with poor OS (Chow et al. 2019). Both populations present with disease burden or aggressive cancer prior to CAR-T cell therapy, possibly having been referred too late in the course of treatment or waited too long before CAR-T cells were processed for them. Both of these issues have potential solutions, such as more widely publicizing the efficacy of CAR-T cells, which may increase referrals at an earlier stage, and developing methods, which are already being heavily investigated, for shortening the manufacturing process (Rafiq et al. 2020). In the latter case, the use of allogeneic lymphocytes could allow for already prepared cells to be readily used when needed and would most likely be the most efficient strategy as long as the risk of graft-versus host disease is offset (Graham and Jozwik 2018). Thus, achieving CR is a crucial step in increasing OS, as patients with partial response (PR) or stable disease (SD) present with lower OS, while currently, recurrence appears to be rare when CR is maintained for more than 6 months (Komanduri 2021). However, the disease will likely recur in more than half of patients in the months following treatment, possibly due to issues such as the poor persistence of CAR-T cells (which may not be as crucial as once thought for acute lymphoblastic leukaemia (Komanduri 2021)) or the loss of target antigen expression (which has been regularly documented (Rafiq et al. 2020)). Both of these mechanisms could potentially be used to develop methods that reduce recurrence after CAR-T cell therapy. In fact, the most popular approaches currently being investigated are attempting to either use two CAR-T cell types that each target different antigens or to create CAR-T cell constructs that target either multiple antigens or an antigen other than CD19 (Shah et al. 2020). The concomitant infusion of CAR-T cells with targeted therapies is also being explored in other B-cell malignancies and appears to both increase the CR rate and decrease recurrence (Gauthier et al. 2020). When recurrence does occur, patient OS is rather dismal, and the best remaining option would most likely be inclusion in a clinical trial. If this option is not available, salvage therapy may be attempted, although cytotoxic treatments are extremely limited given that most diseases have been refractory to numerous lines of treatment prior to immunotherapy. A few case reports and studies with a small patient population receiving anti-PD-1 antibodies, ibrutinib, or ImiDs have been reported with largely anecdotal supporting evidence (Byrne et al. 2019). However, even in the case of a new objective response (OR), the subsequent risk of recurrence is substantial and may invite further consolidation with allogeneic haematopoietic stem cell transplantation (Byrne et al. 2019), which has already been performed in patients treated for acute lymphoblastic leukaemia (Hay et al. 2019). However, the efficacy of this strategy remains to be validated in NHL patients in clinical trials. Further supporting evidence, although limited, has recently been reported concerning an additional treatment with CAR-T cells inducing an OR. Of the 21 NHL patients included in the study, the OR rate after the second infusion was 52% (CR, n = 4; PR, n = 7), with some durable responses inviting further investigations (Gauthier et al. 2021). Overall, with such poor outcomes after recurrence, current efforts are also focused on predicting the patients most likely to experience disease progression and that are potential candidates for preemptive consolidation therapy, although there is no doubt that patients who do not achieve a rapid CR should be the first candidates. Additionally, immune monitoring should encompass not only CAR-T cell survival but also the detection of circulating tumour DNA (Komanduri 2021) because this could aid in detecting subclinical recurrence and in deciding whether consolidation or maintenance therapy should be administered. However, currently, all these approaches are highly speculative and require further clinical study.

Cultured human endothelial cells (HEC) increase their production of plasminogen activator inhibitor (PAI-1) upon stimulation with endotoxin and IL-1, agents that are known to cause an increase in PAI-1 levels in vivo. In order to study the regulation of PAI-1 synthesis at the mRNA level, we isolated a cDNA clone for the human PAI-1 gene from an endothelial expression cDNA library in λ gt 11 by screening with a PAI-1 specific antibody. Three positive cross-hybridizing clones were isolated. The longest insert (1500 bp) was partially sequenced (1000 bp). The sequence was identical to the PAI-1 sequence recently reported by others. The identity of the cDNA clone was further confirmed by comparison with part of the amino acid sequence of PAI-1. For that purpose t-PA-PAI-1 complex was purified from HEC conditioned medium by immunoadsorption to anti-t-PA IgG, and a suitable peptide was sequenced after comparison of the HPLC elution profiles of CNBr digests of t-PA and t-PA-PAI-1 complex. The amino acid sequence (M)FRQFQADFT completely matches the sequence predicted from the cDNA sequence.By hybridization of the cDNA probe to Northern blots of total cellular RNA from human umbilical vein and artery EC (HUVEC, HUAEC), two transcripts of 2.3 and 3 kb were found. Primary HUAEC, incubated for 18 hours in growth medium, produced considerable although variable levels of PAI-1 activity and contained PAI-1 mRNA levels comparable to those found in subcultured HUAEC. When subcultured HUEC were incubated for 6 h with endotoxin, IL-1 or TNF, a 2-fold increase in PAI-1 mRNA was found with each of these mediators. Stimulation of the cells in the presence of cycloheximide resulted in a further increase of the 3 kb PAI-1 transcript. The 3’ end of this transcript contains a 75 bp AT-rich sequence. Similar 3’ AT-rich sequences have been found in mRNA’s for a number of inflammatory mediators and cellular oncogenes, and in some cases it has been shown that removal of the sequence increased mRNA stability. The influence of cyclohex-imid on the larger PAI-1 transcript might be explained by inhibition of synthesis of a specific nuclease that controls the level of mRNA’s harbouring such an AT rich sequence.