Retro Models of the Cisplatin-DNA Cross-link with Carrier Ligands Having sp2 N-donor Triazine Rings

Rapid rotation of guanine base derivatives about Pt–N7 bonds results in fluxional behavior of models of the key DNA intrastrand G–G cross-link leading to anticancer activity of Pt(II) drugs (G = deoxyguanosine). This behavior impedes the characterization of LPtG2 models (L = one bidentate or two cis-unidentate carrier ligands; G = guanine derivative). The objective of this study is to understand the types of conformers formed as L is systematically varied. This work, relevant to Pt(II) anticancer drugs, has evolved from published studies with sp3 N-ligands (e.g., 2,2\u27-bipiperidine), to C2 symmetrical or unsymmetrical sp2 N-ligands having pyridine and/or triazine rings. NMR spectroscopy provided conclusive evidence that LPtG2 (L = 5,5\u27-dimethyl-2,2\u27-bipyridine (5,5\u27-Me2bipy), 3-(4\u27-methylpyridin-2\u27-yl)-5,6-dimethyl-1,2,4-triazine) (MepyMe2t), and bis-3,3\u27-(5,6-dialkyl-1,2,4-triazine) (R4dt)) complexes exist as interconverting mixtures of head-to-tail (HT) and head-to-head (HH) conformers. The triazine rings have a N plus lone pair in the same position as the C6H of pyridine rings, and NMR spectral studies indicate that the LPtG2 adducts are more dynamic when L has a triazine ring. For the first time, the two possible HH conformers (HHa and HHb) were identified for (MepyMe2t)Pt(5\u27-GMP)2, an adduct having an unsymmetrical L. Although O6–O6 clashes involving the two cis G bases favor the HT over the HH arrangement, the HH conformer of (R4dt)Pt(5\u27-GMP)2 adducts has a high abundance (~50%), a finding attributed to a reduction in O6–O6 steric clashes permitted by the overall low steric effects of R4dt ligands. The (R4dt)Pt(d(G*pG*)) adduct (G* = N7 platinated G residue linked with a sugar-phosphodiester backbone), is the first adduct having a high abundance of a fourth form. The characteristics of this form suggest it is the elusive lambda HT conformer; in addition, this adduct had the normally observed HH1, HH2 and delta HT conformers. Studies with the (R4dt)Pt(d(G*pG*)) adducts provided the first clear evidence that the sugar-phosphodiester backbone between two adjacent G’s slows the rate of exchange between the conformers. For (R4dt)Pt(d(G*pG*)), a 3\u27-flanking T has no significant influence on the structure of the d(G*pG*) cross-link or the distribution of conformers, whereas the 5\u27-T residue led to the exclusive presence of the HH1 conformer

Expense Tracker Web Application

Budget Tracker is an easy-to-use daily cost management system, effectively managing daily web- based programs that reduce the need for handy manuals that keep records neatly and easily access user-stored data. The web application "Expense Tracker" is designed to manage daily expenses efficiently and effectively. By using this app we can reduce hand counts for daily expenses and track expenses. In this application, the user can give his salary to calculate his total cost per day and these results will be stored for each user. The app has a system for predicting the income and expenses of a manager using data mining. In this application, there are 3 entries such as manager, manager and employees. Administrator reserves the right to add, edit, remove manager, add, edit, remove employees, and receive all custom reports. To the Administrator, the rights are to increase the type of expenditure, verify costs, increase revenue type, verify revenue and generate reports. For employees, the rightsto add and arrange costs,income and statistics, and shipping to be guaranteed

Impact of Emotional Intelligence on Job Performance of Nurses with the Mediating Effect of Job Satisfaction

The current study investigates the effect of Emotional Intelligence (EI) on the performance of nurses with the mediating effect of job satisfaction. This study measures the concept of EI, Job Performance, and Job Satisfaction across 385 respondents from various private and government hospitals and the locale of the study was the Delhi NCR region. PLS-SEM was used for analyzing the data. The result indicates that a relationship exists between these three variables and job satisfaction mediates the relationship between Emotional Intelligence & Job performance. The findings of the current study showed that awareness of emotions, regulation of emotions, and managing of emotions are the significant components of EI which enhances leadership, critical care, professional development, interpersonal relationships, planning and collaboration aspects of Job Performance. Further, the mediating effects support that the positive working conditions and organizations’ compensation policy fetches higher level of Job Satisfaction among the professional and nursing employees who are satisfied as well as having a higher level of Emotional Quotient would be a better performer than the employees who are having a low level of emotional intelligence. It can be recommended that while recruiting nursing employees along with their technical competence EI competence needs to be equally emphasized. Similarly, EI needs to be integrated into healthcare practice guidelines and performance evaluations as it is one of the important assets of individual persona

Neglected bidentate sp2 N-donor carrier ligands with triazine nitrogen lone pairs: platinum complexes retromodeling cisplatin guanine nucleobase adducts

Rapid rotation of guanine base derivatives about Pt-N7 bonds results in fluxional behavior of models of the key DNA intrastrand G-G cross-link leading to anticancer activity of Pt(II) drugs (G = deoxyguanosine). This behavior impedes the characterization of LPtG2 models (L = one bidentate or two cis-unidentate carrier ligands; G = guanine derivative not linked by a phosphodiester group). We have examined the formation of LPtG2 adducts with G = 5\u27- and 3\u27-GMP and L = sp(2) N-donor bidentate carrier ligands [5,5\u27-dimethyl-2,2\u27-bipyridine (5,5\u27-Me2bipy), 3-(4\u27-methylpyridin-2\u27-yl)-5,6-dimethyl-1,2,4-triazine) (MepyMe2t), and bis-3,3\u27-(5,6-dialkyl-1,2,4-triazine) (R4dt)]. NMR spectroscopy provided conclusive evidence that these LPt(5\u27-GMP)2 complexes exist as interconverting mixtures of head-to-tail (HT) and head-to-head (HH) conformers. For a given G, the rates of G base rotation about the Pt-N7 bonds of LPtG2 models decrease in the order Me4dt \u3e Et4dt \u3e MepyMe2t \u3e 5,5\u27-Me2bipy. This order reveals that the pyridyl ring C6 atom + H atom grouping is large enough to impede the rotation, but the equivalently placed triazine ring N atom + N lone pair grouping is sterically less impeding. For the first time, the two possible HH conformers (HHa and HHb) in the case of an unsymmetrical L have been identified in our study of (MepyMe2t)Pt(5\u27-GMP)2. Although O6-O6 clashes involving the two cis G bases favor the HT over the HH arrangement for most LPtG2-type complexes, the HH conformer of (R4dt)Pt(5\u27-GMP)2 adducts has a high abundance (approximately 50%). We attribute this high abundance to a reduction in O6-O6 steric clashes permitted by the overall low steric effects of R4dt ligands. Under the reaction conditions used, 3\u27-GMP forms a higher abundance of the LPt(GMP)2 adduct than does 5\u27-GMP, a result attributable to more favorable second-sphere communication in the LPt(3\u27-GMP)2 adduct than in the LPt(5\u27-GMP)2 adduct

Investigation relevant to the conformation of the 17-membered Pt(d(GpG)) macrocyclic ring formed by Pt anticancer drugs with DNA: Pt complexes with a Goldilocks carrier ligand

Platinum anticancer drug DNA intrastrand cross-link models, LPt(d(G*pG*)) (G* = N7-platinated G residue, L = R(4)dt = bis-3,3\u27-(5,6-dialkyl)-1,2,4-triazine), and R = Me or Et), undergo slow Pt-N7 bond rotation. NMR evidence indicated four conformers (HH1, HH2, ΔHT1, and ΛHT2); these have different combinations of guanine base orientation (head-to-head, HH, or head-to-tail, HT) and sugar-phosphodiester backbone propagation relative to the 5\u27-G* (the same, 1, or opposite, 2, to the direction in B DNA). In previous work on LPt(d(G*pG*)) adducts, Pt-N7 rotation was too rapid to resolve conformers (small L with bulk similar to that in active drugs) or L was too bulky, allowing formation of only two or three conformers; ΛHT2 was not observed under normal conditions. The (R(4)dt)Pt(d(G*pG*)) results support our initial hypothesis that R(4)dt ligands have Goldilocks bulk, sufficient to slow G* rotation but insufficient to prevent formation of the ΛHT2 conformer. Unlike the (R(4)dt)Pt(5\u27-GMP)(2) adducts, ROESY spectra of (R(4)dt)Pt(d(G*pG*)) adducts showed no EXSY peaks, a result providing clear evidence that the sugar-phosphodiester backbone slows conformer interchange. Indeed, the ΛHT2 conformer formed and converted to other conformers slowly. Bulkier L (Et(4)dt versus Me(4)dt) decreased the abundance of the ΛHT2 conformer, supporting our initial hypothesis that steric crowding disfavors this conformer. The (R(4)dt)Pt(d(G*pG*)) adducts have a low abundance of the ΔHT1 conformer, consistent with the proposal that the ΔHT1 conformer has an energetically unfavorable phosphodiester backbone conformation; its high abundance when L is bulky is attributed to a small d(G*pG*) spatial footprint for the ΔHT1 conformer. Despite the Goldilocks size of the R(4)dt ligands, the bases in the (R(4)dt)Pt(d(G*pG*)) adducts have a low degree of canting, suggesting that the ligand NH groups characteristic of active drugs may facilitate canting, an important aspect of DNA distortions induced by active drugs

Ligand and coordination-plane distortions in platinum(II) complexes of isomers of dimethyl-2,2\u27-bipyridine

Pseudo-square-planar platinum(II) complexes containing 4,4\u27 (4,4\u27-Me(2)bipy), 5,5\u27 (5,5\u27-Me(2)bipy) and 6,6\u27 (6,6\u27-Me(2)bipy) isomers of dimethyl-2,2\u27-bipyridine (Me(2)bipy) were synthesized and structurally characterized to assess the effects of methyl-group position on structure. The Pt-N distances in (Me(2)bipy)PtCl(2) complexes fall in the typical range [2.017 (3)-2.032 (3) Angstroms]. Only minor distortions such as 2.4 and 5.5 degrees twisting of the two pyridyl rings in (4,4\u27-Me(2)bipy)PtCl(2) (I) and (5,5\u27-Me(2)bipy)PtCl(2) (II), respectively, occur. However, (6,6\u27-Me(2)bipy)PtCl(2) (III) is highly distorted: the two pyridyl rings in (III) have a large bowing angle (theta(B)) of 19.2 degrees . The presence of distortions in (III), but not in (I) and (II), is attributed to repulsions between the 6,6\u27-methyl groups and the cis chloro ligands. [(4,4\u27-Me(2)bipy)(2)Pt](BF(4))(2) (IV) undergoes a bow-incline deformation having a large theta(B) value (24.2 degrees), and the ligands are inclined relative to the coordination plane by 18.80 (13) degrees. Complex (IV) joins a small list of distorted bis-bipyridine complexes; this finding can be attributed to the unfavorable repulsions between the 6,6\u27 hydrogen substituents of opposing ligands. Some of these complexes exhibit canting rather than bow-incline distortion, a trend suggesting that subtle solid-state effects determine the nature of the distortion

Chemistry of HIV-1 virucidal Pt complexes having neglected bidentate sp2 N-donor carrier ligands with linked triazine and pyridine rings. synthesis, NMR spectral features, structure, and reaction with guanosine

Complexes of the types LPtCl2 and [L2Pt]X2 [L = substituted 3-(pyridin-2\u27-yl)-1,2,4-triazine] were synthesized and characterized by NMR spectroscopy and, for the first time, by X-ray crystallography in an effort to determine the coordination properties of this novel class of inorganic medicinal agents possessing HIV-1 virucidal activity. The agents containing either one or two sp2 N-donor bidentate ligands are referred to as ptt (platinum triazine) agents. The X-ray structures of three LPtCl2 compounds revealed the expected pseudo-square-planar geometry. The X-ray structure of [(pyPh2t)2Pt](BF4)2 [pyPh2t = 3-(pyridin-2\u27-yl)-5,6-diphenyl-1,2,4-triazine] has the expected trans relationship of the unsymmetrical L and is essentially planar, an unusual property for a Pt(II) complex with two bidentate sp2 N donors. HIV-1 is an RNA virus; the guanosine ribonucleoside (Guo) binds (MepyMe2t)PtCl2 at both (inequivalent) available coordination sites to form [(MepyMe2t)Pt(Guo)2]2+ [MepyMe2t = 3-(4\u27-methylpyridin-2\u27-yl)-5,6-dimethyl-1,2,4-triazine]. This adduct has four nearly equally intense Guo H8 signals attributed to two pairs of head-to-tail (HT) and head-to-head (HH) conformers, which interchange rapidly within each pair. However, equilibration between pairs requires rotation of the Guo cis to the MepyMe2t pyridyl ring, and the H6\u27 proton on this ring projects toward the Guo and hinders Guo rotation about the Pt-N7 bond. Thus, the HT/HH pairs do not interchange; such behavior is rare. Guo did not add to [(MepyMe2t)2Pt]2+, a result suggesting the possibility that the virucidal activity of LPtCl2 and [L2Pt]2+ ptt agents arises respectively from covalent and noncovalent (possibly intercalative interactions favored by [L2Pt]2+ planarity) binding to biomolecular targets

Abstracts of Scientifica 2022

This book contains the abstracts of the papers presented at Scientifica 2022, Organized by the Sancheti Institute College of Physiotherapy, Pune, Maharashtra, India, held on 12–13 March 2022. This conference helps bring researchers together across the globe on one platform to help benefit the young researchers. There were six invited talks from different fields of Physiotherapy and seven panel discussions including over thirty speakers across the globe which made the conference interesting due to the diversity of topics covered during the conference. Conference Title:  Scientifica 2022Conference Date: 12–13 March 2022Conference Location: Sancheti Institute College of PhysiotherapyConference Organizer: Sancheti Institute College of Physiotherapy, Pune, Maharashtra, Indi