High Risk of Secondary Infections Following Thrombotic Complications in Patients With COVID-19

Background. This study’s primary aim was to evaluate the impact of thrombotic complications on the development of secondary infections. The secondary aim was to compare the etiology of secondary infections in patients with and without thrombotic complications. Methods. This was a cohort study (NCT04318366) of coronavirus disease 2019 (COVID-19) patients hospitalized at IRCCS San Raffaele Hospital between February 25 and June 30, 2020. Incidence rates (IRs) were calculated by univariable Poisson regression as the number of cases per 1000 person-days of follow-up (PDFU) with 95% confidence intervals. The cumulative incidence functions of secondary infections according to thrombotic complications were compared with Gray’s method accounting for competing risk of death. A multivariable Fine-Gray model was applied to assess factors associated with risk of secondary infections. Results. Overall, 109/904 patients had 176 secondary infections (IR, 10.0; 95% CI, 8.8–11.5; per 1000-PDFU). The IRs of secondary infections among patients with or without thrombotic complications were 15.0 (95% CI, 10.7–21.0) and 9.3 (95% CI, 7.9–11.0) per 1000-PDFU, respectively (P = .017). At multivariable analysis, thrombotic complications were associated with the development of secondary infections (subdistribution hazard ratio, 1.788; 95% CI, 1.018–3.140; P = .043). The etiology of secondary infections was similar in patients with and without thrombotic complications. Conclusions. In patients with COVID-19, thrombotic complications were associated with a high risk of secondary infections

1,4,8,11-Tetraazacyclotetradecane-5,7-dione (dioxocyclam) copper(II) and aqueous copper(III) complexes

Dioxocyclam (H2L = 1,4,8,11-tetraazacyclotetradecane-5,7-dione), prepd. from di-Et malonate and 1,9-diamino-3,7-diazanonane, was reacted with Cu(OAc)2.H2O in aq. EtOH to give CuL. CuL was electrochem. or chem. (by K2S2O8) oxidized to [CuL]+

Stepwise incorporation of copper(II) into a double-ring octaaza macrocycle and consecutive oxidation to the trivalent state

The double-ring octaaza macrocycle bisdioxocyclam (I) was prepd. by the single-step aminolytic condensation of the appropriate tetraester and linear tetraamine in 1:2 molar ratio. The complexation of Cu(II) by I in aq. soln. was studied by potentiometry. Monometallic and dimetallic complex species form according to the ligand:metal ratio. In general, incorporation of Cu(II) ion into each tetraaza subunit promotes a simultaneous deprotonation of the 2 amido groups. The log k values of complexation equil. are compared with those for the ref. single-ring tetraaza macrocycle dioxocyclam. The [CuII2(bisdioxocyclamato(4-))] complex undergoes a reversible oxidn. to the dicopper(III) complex through 2 consecutive 1-electron steps, whose electrode potentials are sepd. by 110 mV

Dicopper(II) and dicopper(III) complexes with a double-ring octaaza macrocycle

The bicyclic amine I was prepd. in 30% yield by condensation of tetra-Et 1,1,2,2-ethanetetracarboxylate with 1,4,8,11-tetraazaundecane in refluxing EtOH for 2 days and formed a 1:2 complex with Cu2+ in aq. soln. The 2Cu2+-I complex showed weak metal-metal interaction and was easily oxidized to the trivalent state by 2 consecutive one-electron steps sepd. by 110 mV

σ and π Effects on the copper(II)/copper(I) redox couple potential in tetraazamacrocyclic complexes

The electrochem. redn. was studied of Cu(II) complexes with 14 membered tetraaza macrocycles with different structural features and different degrees of unsatn. Each complex undergoes a reversible 1-electron redn. at the Hg electrode in MeOH contg. 0.1 M Et4NBF4. The Cu(II)/Cu(I) process in macrocycles systems can be promoted through modification of the ligands that (a) reduce its σ-donor ability by destabilizing Cu(II) and (b) increase its π-acceptor properties by stabilizing Cu(I). Geometrical effects favorable to formation of Cu(I) can be induced in a fixed coplanar array of 4 N atoms by rearranging the system of fused chelate rings

Entropy contribution to the nickel(III)/nickel(II) redox change in six-coordinating systems. Investigation of the role of the negative charge of the ligand in the stabilization of high oxidation states of the metal center

Entropy changes ΔS°rc assocd. with the 2 half-reactions (i) [NiIIIL2]3+ + e- = [NiIIL2]2+ and (ii) [NiIIIY]0 + e- = [NiIIY] (L = 1,4,7-triazacyclononane H3Y = 1,4,7-triazacyclononane-N,N',N''-triacetic acid) were detd. through the investigation of the temp. dependence of the E1/2(NiIII/NiII) parameter over the 0.1-3.5M concn. range of the background electrolyte (NaCl). The ΔS°rc for half-reaction (i) is pos., and its value decreases with an increasing concn. of the supporting electrolyte, whereas ΔS°rc for half-reaction ii is neg. and its value increases (becoming less neg.) with an increasing concn. of NaCl. The above results were interpreted in terms of variation in the size of the hydration sphere of the electroactive species, which are related to changes of the elec. charge on the complexes. In particular, it was shown that such polyneg. charged ligands as Y3- favor access to unusually high oxidn. states of the metal center due a very favorable entropy term: this reflects a substantial increase of translational entropy, assocd. with the release of H2O mols. from the hydration sphere of the complex during the [NiIIY]/[NiIIIY]0 oxidn. proces

Metal complexes that transport electrons across liquid membranes

Lipophilic metal complexes (displaying 1-electron redox activity) are used as carriers for the transport of electrons across bulk liq. membranes from an aq. reducing phase to an aq. oxidizing phase. The [FeIII,II(bpy)2]3=/2+ redox system (bpy = 4,4'-di-tert-butyl-2,2'-dipyridyl) transports electrons from both cationic and anionic aq. reducing agents to aq. Ce(IV) and counter-transports perchlorate ions in the opposite direction. Electron/chloride ion cross transport between aq. persulfate and aq. metal centered reducing agents, mediated by the membrane dissolved [NiII,IIILCl2]2+/3+ redox system (L = (N-cetylcyclam) takes place at a much higher rate. The overall transport rate in the 2 types of expts. controlled by that of the redox process occurring at the membrane/aq. reducing phase interface and is to be related to the type of mechanism (inner or outer sphere) by which the 2-phase electron transfer process takes place

Metal complexes that transport electrons across liquid membranes: the iron [FeII,IIIL3]2+,3+ redox system (L = 4,4'-di-tert-butyl-2,2'-bipyridine)

Lipophilic [FeL3][ClO4]2 (L = 4,4'-di-tert-butyl-2,2'-bipyridine) was prepd. to be used as a carrier for the transport of electrons from an aq. oxidizing phase to an aq. reducing phase, sepd. by a CH2Cl2 bulk liq. membrane. Two-phase redox expts. indicated that CH2Cl2-dissolved [FeL3][ClO4]2 is oxidized by aq. CeIv to give [FeL3][ClO4]3. [FeL3][ClO4]3 was reduced, under 2-phase conditions, by a series of aq. reducing agents according to the rate sequence: NO2- > [Fe(CN)64- > FeII > SO32-. Three-phase expts. were carried out in which electrons are transported by [FeL3][ClO4]2 from the aq. reducing phase to the aq. phase contg. CeIV, across the bulk liq. membrane, and ClO4- ions are transported by [FeL3][ClO4]3 in the opposite direction. The rate of the electron transport is controlled by the rate of the slowest of the 2 redox processes at the 2 sides of the membrane. By varying the concns. of the aq. reactants, it is possible to det. the 2-phase rate-detg. step of the overall 3-phase process and to perform selective oxidn. by CeIV of the investigated reducing agents

Ring-size effects on the formation of dicopper(II) and dicopper(III) complexes with bimacrocycles, 13- and 14-membered tetraaza subunits

The double-ring macrocycle I, having 13-membered subunits, incorporates 2 CuII ions in aq. soln. in 3 pH-controlled steps, which involve progressive deprotonation of the coordinated amido groups of the ligand. The fully deprotonated neutral dicopper(II) complex undergoes a reversible oxidn. process to the dicopper(III) species according to 2 1-electron redox changes sepd. by 100 mV. This behavior is compared with that of the corresponding bimacrocyclic ligand having 14-membered subunits as well as with single-ring ref. systems. The 14-membered subunit forms the more stable complexes with CuII ion, whereas the 13-membered cavity favors the access to the trivalent state, with both single- and double-ring systems