Low-Migration Compounds with Amine Functionality as Coinitiators of Radical Polymerization.

The utilization of two-component systems comprising camphorquinone (CQ) and aromatic amines has become prevalent in the photopolymerization. However, there are still concerns about the safety of this CQ/amine system, mainly because of the toxicity associated with the leaching of aromatic amines. In light of these concerns, this study aims to develop novel coinitiator combinations featuring CQ and amines which cannot be leached out of materials, enabling free radical polymerization of representative dentalmethacrylate resins under blue light irradiation. This approach involves the initial design and analysis of hydrogen donors with low C─H bond dissociation energy through molecular modeling. Subsequently, copolymerizable methacrylate functional groups are incorporated via chemical modification, allowing it to act as both coinitiator and copolymerization monomer to achieve low migrationand leachability properties. This work presents, for the first time, the synthesis of the innovative coinitiator and compares its performance with the benchmark CQ/ethyl-4-dimethylaminobenzoate (EDB)-based photoinitiation system (PIS). The results demonstrate the effectiveness of the newly proposed PIS. Finally, an in-depth investigation is conducted into the reaction mechanism associated with this PIS through molecular orbital calculations and electron spin resonance studies.

Chemoradiotherapy plus hyperthermia (CRTH) versus chemoradiotherapy (CRT) alone in neoadjuvant treatment of soft tissue sarcoma: tumor response, treatment toxicity and disease control.

INTRODUCTION: Neoadjuvant chemotherapy and radiotherapy for the management of soft tissue sarcomas (STS) are still preferably delivered sequentially, with or without concurrent hyperthermia. Concurrent delivery of chemo-, radio- and thermotherapy may produce synergistic effects and reduce chemotherapy-free intervals. The few available studies suggest that concurrent chemoradiation (CRT) has a greater local effect. Data on the efficacy and toxicity of adding hyperthermia to CRT (CRTH) are sparse. MATERIALS AND METHODS: A cohort of 101 patients with STS of the extremities and trunk who received CRT (n = 33) or CRTH (n = 68) before resection of macroscopic tumor (CRT: n = 19, CRTH: n = 49) or re-resection following a non-oncological resection, so called 'whoops procedure', (CRT: n = 14, CRTH: n = 19) were included in this retrospective study. CRT consisted of two cycles of doxorubicine (50 mg/m2 on d2) plus ifosfamide (1500 mg/m2 on d1-5, q28) plus radiation doses of up to 60 Gy. Hyperthermia was delivered in two sessions per week. RESULTS: All patients received the minimum dose of 50 Gy. Median doses of ifosfamide and doxorubicin were comparable between CRT (75%/95%) and CRTH (78%/97%). The median number of hyperthermia sessions was seven. There were no differences in acute toxicities. Major wound complications occurred in 15% (CRT) vs. 25% (CRTH) (p = 0.19). In patients with macroscopic disease, the addition of hyperthermia resulted in a tendency toward improved remission: regression ≥90% occurred in 21/48 (CRTH) vs. 4/18 (CRT) patients (p = 0.197). With a median postoperative follow-up of 72 months, 6-year local control and overall survival rates for CRTH vs. CRT alone were 85 vs. 78% (p = 0.938) and 79 vs. 71% (p = 0.215). CONCLUSIONS: Both CRT and CRTH are well tolerated with an expected rate of wound complications. The results suggest that adding hyperthermia may improve tumor response.

Long-Term Follow-Up of Patients Receiving Neoadjuvant Treatment Modalties for Soft Tissue Sarcomas of the Extremities.

BACKGROUND: Neoadjuvant treatment modalities in soft tissue sarcoma (STS) of the extremities have become more popular in recent years, but because of the rarity and heterogeneity of STS, there are yet few studies on the long-term impact of neoadjuvant treatment modalities, especially in terms of neoadjuvant radiochemotherapy. METHODS: The study enrolled 136 patients with primary STS of the extremities who underwent surgery with curative intent or neoadjuvant therapy, followed by surgery in a 15-year period. Neoadjuvant treatment consisted of radiotherapy (RT) with 60 Gy and in most cases simultaneous chemotherapy (CTx) with ifosfamide (1.5 g/m2/d, d1-5, q28) and doxorubicine (50 mg/m2/d, d3, q28). We investigated the clinical, (post)-operative and histopathological data and the oncological follow-up as well. The median follow-up period was 82 months (range 6-202). RESULTS: A total of 136 patients (M:F = 73:63) with a mean age of 62 years (range; 21-93) was observed. Seventy-four patients (54.4%) received neoadjuvant therapy (NT), 62 patients (45.6%) received primary surgery (PS). When receiving NT, patients with high-risk STS had a lower risk to develop distant metastasis (p = 0.025). Age, histological type, tumor size and surgical margins (R0 vs. R1) had no influence on any survival rates. There was an association between NT and the occurrence of postoperative complications (p = 0.001). The 5-year local recurrence free survival (LRFS), metastasis free survival (MFS), disease free survival (DFS) and overall survival (OS) rate of the whole cohort was 89.9%, 77.0%, 70.6% and 72.6%; whereas the 5-year LRFS, MFS, DFS and OS rate was 90.5%, 67.2%, 64.1% and 62.8% for the NT group and 89.5%, 88.3%. 78.4% and 83.8% for the PS group. CONCLUSIONS: Multimodal treatment strategies in patients with STS of extremities lead to excellent oncological outcomes. Patients with high-risk STS had a significantly better MFS when receiving NT than patients with low-risk STS. NT was associated with a higher probability of postoperative but well-manageable complications.

Structural variations and molecular dynamics of rare-earth metal complexes with the N,N-bis(2-{pyrid-2-yl}ethyl)hydroxylaminato ligand.

The reaction of the donor-functionalised N,N-bis(2-{pyrid-2-yl}ethyl)hydroxylamine and [LnCp3] (Cp=cyclopentadiene) resulted in the formation of bis(cyclopentadienyl) hydroxylaminato rare-earth metal complexes of the general constitution [Ln(C5H5)2{ON(C2H4-o-Py)2}] (Py=pyridyl) with Ln=Lu (1), Y (2), Ho (3), Sm (4), Nd (5), Pr (6), La (7). These compounds were characterised by elemental analysis, mass spectrometry, NMR spectroscopy (for compounds 1, 2, 4 and 7) and single-crystal X-ray diffraction experiments. The complexes exhibit three different aggregation modes and binding motifs in the solid state. The late rare-earth metal atoms (Lu, Y, Ho and Sm) form monomeric complexes of the formula [Ln(C5H5)2{eta2-ON(C2H4-eta1-o-Py)(C2H4-o-Py)}] (1-4, respectively), in which one of the pyridyl nitrogen donor atoms is bonded to the metal atom in addition to the side-on coordinating hydroxylaminato unit. The larger Nd3+ and Pr3+ ions in 5 and 6 make the hydroxylaminato unit capable of dimerising through the oxygen atoms. This leads to the dimeric complexes [(Ln(C5H5)2{mu-eta1:eta2-ON(C2H4-o-Py)2})2] without metal-pyridine bonds. Compound 7 exhibits a dimeric coordination mode similar to the complexes 5 and 6, but, in addition, two pyridyl functions coordinate to the lanthanum atoms leading to the [(La(C5H5)2{ON(C2H4-o-Py)}{mu-eta1:eta2-ON(C2H4-eta1-o-Py)})2] complex. The aggregation trend is directly related to the size of the metal ions. The complexes with coordinative pyridine-metal bonds show highly dynamic behaviour in solution. The two pyridine nitrogen atoms rapidly change their coordination to the metal atom at ambient temperature. Variable-temperature (VT) NMR experiments showed that this dynamic exchange can be frozen on the NMR timescale.

Transformation of hydroxylamide into hydrazide units in the coordination spheres of group 4 metals.

Hydroxylamine units, bonded via their oxygen atom to a cyclo-pentadienyldimethylsilyl group are transformed into siloxy ligands and hydrazide units by the reaction with tetrakis(dimethylamido)-titanium and -zirconium by the same reaction principle but resulting in different aggregates of the products.

Syntheses and structures of (N',N'-dimethylhydrazido)silanes.

The hydrazidosilanes Ph(2)Si(NHNMe(2))(2) (1), Me(2)Si(NHNMe(2))(2) (2), PhSi(NHNMe(2))(3) (3), MeSi(NHNMe(2))(3) (4), PhClSi(NHNMe(2))(2) (5), MeClSi(NHNMe(2))(2) (6), Me(2)ClSi(NHNMe(2)) (7), MeClHSi(NHNMe(2)) (8), MeHSi(NHNMe(2))(2) (9), Me(2)HSi(NHNMe(2)) (10), Me(2)NN[HSi(NHNMe(2))(2)](2) (11) and Si(NHNMe(2))(4) (12) have been prepared by the reaction of the corresponding chlorosilanes with N,N-dimethylhydrazine. Some of the compounds containing Si-Cl and N-H functions simultaneously (6,7,8 ) are very reactive and tend to polymerise and could only be characterised by spectroscopic methods ((1)H, (13)C, (29)Si NMR, IR, MS). All other compounds could additionally be characterised by elemental analyses. The structures of , , , , and in the solid state were determined by X-ray diffraction. These include the first structural determinations of compounds containing SiH-NH-N (9,11) and SiCl-NH-N (5) units.

Bis-hydroxylaminato group 4 half-sandwich complexes-syntheses, structures and polymerisation activity studies.

The methylene- and ethylene-bridged bis-hydroxylamines HONMe(CH(2))(n)NMeOH (n = 1, 2) were reacted with [Cp*TiCl(3)], [Cp*ZrCl(3)] and [Cp*HfCl(3)] in the presence of MeLi to give the complexes [Cp*TiMe{(eta(2)-ONMe)(2)CH(2)}] (), [Cp*TiMe{(eta(2)-ONMeCH(2))(2)}] (), [Cp*ZrMe{(eta(2)-ONMeCH(2))(2)}] () and [Cp*HfMe{(eta(2)-ONMeCH(2))(2)}] (). The reaction of with AlMe(3) afforded the adduct [Cp*TiMe{eta(2)-[O(AlMe(3))NMe]CH(2)CH(2)-eta(2)-(NMeO)}] (.AlMe(3)). The compounds were characterised by NMR spectroscopy, elemental analyses and mass spectrometry. Their crystal structures were determined by X-ray diffraction. In each case, all four donor atoms of the [2 + 2]-dentate ligands coordinate in a eta(2)-manner to the organometallic [Cp*MMe] complex fragments. The polymerisation reactions of ethylene and propylene catalysed by activated with methylalumoxane (MAO) were examined.

Bis(hydroxylaminato)-mono(pentamethylcyclopentadienyl) rare-earth metal complexes.

Salt metathesis reactions involving the anhydrous rare-earth metal trichlorides MCl(3) (M = Y, Ho, Er and Lu) and the N,N-diethylhydroxylaminato potassium salt, KONEt(2) (1), and KC(5)Me(5) result in formation of rare-earth metal hydroxylaminato complexes of the type [(C(5)Me(5))M(mu-eta(1):eta(2)-ONEt(2))(eta(2)-ONEt(2))](2) (M = Y (2a), Ho (2b), Er (2c) and Lu (2d)). Compound 1 was characterised by elemental analysis, compounds 2a and 2d by NMR spectroscopy and compounds 2a-d by elemental analyses, mass-spectrometry and single crystal X-ray diffraction. Compounds 2a-d are isostructural in the solid state. Effective saturation of the coordination sphere of the rare-earth metal atoms by the hydroxylaminato groups is achieved by the formation of three-membered MON rings.

Neutral ligand induced methane elimination from rare-earth metal tetramethylaluminates up to the six-coordinate carbide state.

The reaction of 1,3,5-trimethyl-1,3,5-triazacyclohexane (TMTAC) with [La{Al(CH(3))(4)}(3)] resulted in C-H activation, leading to the formation of [(TMTAC)La{Al(CH(3))(4)}{(mu(3)-CH(2))[Al(CH(3))(2)(mu(2)-CH(3))](2)}] (1) containing a bis(aluminate) dianion and subsequent extrusion of methane. A similar reaction with [Y{Al(CH(3))(4)}(3)] led to the formation of CH(4), [TMTAC{Al(CH(3))(3)}(2)] (2) and {[(TMTAC)Y][Y(2)(mu(2)-CH(3))][{(mu(6)-C)[Al(mu(2)-CH(3))(2)(CH(3))](3)}{(mu(3)-CH(2))(mu(2)-CH(3))Al(CH(3))(2)}(2)] (3), containing a six-coordinate carbide ion and two [CH(2)Al(CH(3))(3)](2)(-) anions. Compound 3 is a product of multiple C-H activation. This reaction was monitored by in situ(1)H NMR spectroscopy. The analogous reaction with [Sm{Al(CH(3))(4)}(3)] led to the formation of 2, of [(TMTAC)Sm{(mu(2)-CH(3))(CH(3))(2)Al}(2){(mu(3)-CH(2))(2)Al(CH(3))(2)}(2)] (4), which contains a tris(aluminate) trianion, and [{(TMTAC)Sm}{Sm(2)(mu(2)-CH(3))}{(mu(6)-C)[Al(mu(2)-CH(3))(2)(CH(3))](3)}{(mu(3)-CH(2))(mu(2)-CH(3))Al(CH(3))(2)}(2)] (5), which is isostructural to 3. The products were characterised by elemental analyses (except 4, 5), 1 by multinuclear NMR spectroscopy and compounds 1, 2, 3, 4 and 5 by X-ray crystallography. Quantumchemical calculations were undertaken to support the crystallographic data analysis and confirm the structure of 3 and to compare it with an analogous compound where the central six-coordinate carbon has been replaced by oxygen. The investigations point to a mechanism of sterically induced condensation of [Al(CH(3))(4)](-) groups in close proximity in the coordination spheres of the rare-earth metal atoms, which is dependent on the size of these metal atoms.

Potassium hydroxylamine complexes.

Potassium complexes of N,N-dialkylhydroxylamines [KONR2, R=Me (1a), iPr (2a), CH2C6H5] were synthesized by the deprotonation of the corresponding N, N-dialkylhydroxylamines with KH. 1a and 1b [(KONMe2)(HONMe2)] dissolve in THF under the addition of an additional equiv of the parent hydroxylamine to give 1b and [(KONiPr2)(HONiPr2)(THF)] 2b. 1b, 2b and [(KONBn2)6(THF)4] (3) were characterized by NMR and IR spectroscopy, by elemental analyses, and by X-ray diffraction of single crystals. 1b and 2b crystallize as polymers, whereby compound 1b with smaller groups leads to higher coordination numbers at the potassium atoms (CN=7) and double-stranded more complex ladder-type aggregates, whereas 2b with the larger iPr groups contains potassium atoms with a coordination number of 5 and is a single-stranded polymer. The compound {[KON(CH2C6H5)2]6(THF)4} (3) exists in a hexameric bis-cubane-based form in the solid state. Quantum chemical calculations were undertaken to examine the nature of the hydrogen bonding in the (R2NO...H...ONR2) units of 1b and 2b, which is asymmetric in the first and symmetric in the second case.

Structural diversity in bishydroxylamine complexes of gallium.

Reactions of bishydroxylamines of the type HON(R)CH2CH2N(R)OH (R=Me, tBu) with trimethyl- and triisopropylgallium gave bicyclic metalla cages of the formula R'2GaO(R)NCH2CH2N(R)OGaR'2 [R'=Me, R=Me (), tBu (); R'=iPr, R=Me (), tBu ()] with six-membered Ga2O2N2-rings. While the complexes show the same core constitution in the solid state, NMR spectra reveal the steric influence of the isopropyl substituent of the compounds / on its behaviour in solution. The reaction of the sterically more demanding substituted tri-tert-butylgallium with HON(Me)CH2CH2N(Me)OH yielded a heterodimeric complex O'-[HON(Me)CH2CH2NH(Me)O(tBu2Ga)]-cyclo-(tBu2Ga)-O,N'-[ON(Me)CH2CH2N(Me)O] () with two gallium atoms of different surrounding and two different bishydroxylamine ligands, one doubly deprotonated and one protonated, but at one end in its tautomeric aminoxide form. Further condensation of was observed to give a tricyclic compound cyclo-[(tBuGa)ON(Me)CH2CH2N(Me)O]2 () with a central Ga2O2N2 ring resulting from two Ga-N donor-acceptor bonds.

Organo-aluminium and -gallium complexes with omega-NH-functional alkoxide ligands.

The aminoalcohols MeNH(CH(2))(2)OH (), (t)BuNH(CH(2))(2)OH (), MeNH(CH(2))(3)OH (), (t)BuNH(CH(2))(3)OH () and MeNHCH(2)CMe(2)CH(2)OAlMe(2) () have been reacted with AlMe(3) to give the five corresponding aminoalkoxides of the general formula RNH-X-AlMe(2)- (X = organic spacer between N and O). (t)BuNHCH(2)CMe(2)CH(2)OH () reacts with AlMe(3) to give [(t)BuNHCH(2)CMe(2)CH(2)OAlMe(2)].AlMe(3) (.AlMe(3)). Analogous reactions of the aminoalcohols , , and with Al(t)Bu(3), GaMe(3) and Ga(t)Bu(3) afforded the corresponding aminoalkoxides of the general formula RNH-X-MR'(2)- (MR'(2) = Al(t)Bu(2)), - (MR'(2) = GaMe(2)) and - (MR'(2) = Ga(t)Bu(2)). The compounds were characterised by NMR spectroscopy, elemental analyses and mass spectrometry. Crystal structures were determined for , , .AlMe(3), , , and . Compounds and dimerise via Al(2)O(2) rings, while the amino-functions form intramolecular Al-N bonds. Compounds and form monomers with intramolecular Ga-N bonds. Compounds and are dimers via Ga(2)O(2) rings but in contrast to and without formation of intramolecular Ga-N bonds. .AlMe(3) also forms a monomeric compound with intramolecular AlN bond and a further AlMe(3) unit bonded to the O atom. The dynamic behaviour of and was investigated by variable-temperature NMR spectroscopy. Some compounds have different aggregation in solid and fluid phases.

Hydroxylaminato yttrate and samarate complexes.

The first homoleptic anions of hydroxylaminato ate-complexes of yttrium and samarium of the formulae K[M(ON(i)Pr(2))(4)] (M = Y, Sm) have been prepared and structurally characterised featuring variations of the hapticity of their ON(i)Pr(2) ligands leading to different chain connectivities in their solid state aggregates.