Cytotoxicity of half sandwich ruthenium(II) complexes with strong hydrogen bond acceptor ligands and their mechanism of action

Neutral and cationic organometallic ruthenium(II) piano stool complexes of the type [(eta(6)-cymene)R-uCl(X)(Y)] (complexes R1-R8) has been synthesized and characterized. In cationic complexes, X, Y is either a eta(2) phosphorus ligand such as 1,1-bis(diphenylphosphino)methane (DPPM) and 1,2-bis(diphenylphosphino)ethane (DPPE) or partially oxidized ligands such as 1,2-bis(diphenylphosphino)methane monooxide (DPPMO) and 1,2-bis(diphenylphosphino)ethane monooxide (DPPEO) which are strong hydrogen bond acceptors. In neutral complexes. X is chloride and Y is a monodentate phosphorous donor. Complexes with DPPM and DPPMO ligands ([(eta(6)-cymene)Ru(eta(2)-DPPM)Cl]PF6 (R2), [(eta(6)-cymene)Ru(eta(2)-DPPMO)Cl]PF6 (R3), [(eta(6)-cymene)Ru(eta(1)-DPPM)Cl-2] (R5) and [(eta(6)-cymene)Ru(eta(1)-DPPMO)Cl-2] (R6) show good cytotoxicity. Growth inhibition study of several human cancer cell lines by these complexes has been carried out. Mechanistic studies for R5 and R6 show that inhibition of cancer cell growth involves both cell cycle arrest and apoptosis induction. Using an apoptosis PCR array, we identified the sets of antiapoptotic genes that were down regulated and pro-apoptotic genes that were up regulated. These complexes were also found to be potent metastasis inhibitors as they prevented cell invasion through matrigel. The complexes were shown to bind DNA in a non intercalative fashion and cause unwinding of plasmid DNA in cell-free medium by competitive ethidium bromide binding, viscosity measurements, thermal denaturation and gel mobility shift assays.

‘Enough is enough’: Songs and messages about alcohol in remote Central Australia

This article examines some of the ways in which Australia’s First Peoples have responded to serious community health concerns about alcohol through the medium of popular music. The writing, performing and recording of popular songs about alcohol provide an important example of community-led responses to health issues, and the effectiveness of music in communicating stories and messages about alcohol has been recognised through various government-funded recording projects. This article describes some of these issues in remote Australian Aboriginal communities, exploring a number of complexities that arise through arts-based ‘instrumentalist’ approaches to social and health issues. It draws on the author’s own experience and collaborative work with Aboriginal musicians in Tennant Creek, a remote town in Australia’s Northern Territory.

Anticancer Activity of Hydrogen-Bond-Stabilized Half-Sandwich RuII Complexes with Heterocycles

Neutral half-sandwich organometallic ruthenium(II) complexes of the type (?6-cymene)RuCl2(L)] (H1H10), where L represents a heterocyclic ligand, have been synthesized and characterized spectroscopically. The structures of five complexes were also established by single-crystal X-ray diffraction confirming a piano-stool geometry with ?6 coordination of the arene ligand. Hydrogen bonding between the N?H group of the heterocycle and a chlorine atom attached to Ru stabilizes the metalligand interaction. Complexes coordinated to a mercaptobenzothiazole framework (H1) or mercaptobenzoxazole (H6) showed high cytotoxicity against several cancer cells but not against normal cells. In vitro studies have shown that the inhibition of cancer cell growth involves primarily G1-phase arrest as well as the generation of reactive oxygen species (ROS). The complexes are found to bind DNA in a non-intercalative fashion and cause unwinding of plasmid DNA in a cell-free medium. Surprisingly, the cytotoxic complexes H1 and H6 differ in their interaction with DNA, as observed by biophysical studies, they either cause a biphasic melting of the DNA or the inhibition of topoisomerase IIa activity, respectively. Substitution of the aromatic ring of the heterocycle or adding a second hydrogen-bond donor on the heterocycle reduces the cytotoxicity.

Substitution-Modulated Anticancer Activity of Half-Sandwich Ruthenium(II) Complexes with Heterocyclic Ancillary Ligands

Ten new organometallic half-sandwich ruthenium complexes with heterocyclic ligands have been synthesized (H1-H10). The substituents on the ancillary heterocyclic ligands were varied to understand the effect of substitution on anticancer activity. The crystallographic characterization of five complexes confirms that they adopt three-legged piano-stool structures and are stabilized by intramolecular hydrogen bonding. Complexes H2 and H3 also exhibit halogen bonding in the solid state. In aqueous media, the complexes form dinuclear ruthenium species. Complex H1 with a noncytotoxic heterocycle, 6-fluoro-2-mercaptobenzothiazole, and complex H11 with the unsubstituted 2-mercaptobenzothiazole are the most active against A2780 and KB cell lines. The substitution of the H atoms on the ancillary ligand with Cl or Br atoms leads to a decrease in the anticancer activity. With the exception of fluorine-substituted H5, the complexes with mercaptobenzoxazole (H6-H9) are inactive against all of the tested cell lines. Ruthenium complexes with mercaptonaphthimidazole (H10) and mercaptobenzimidazole (H13) do not show any anticancer activity. The active complexes show a biphasic melting curve when incubated with calf thymus (CT) DNA. These complexes only inhibit thioredoxin reductase (TrxR) enzyme activity to a small extent. The substitution of hydrogen atoms with fluorine atoms in the aromatic heterocyclic ligands on organometallic half-sandwich ruthenium complexes has the most beneficial effect on their anticancer activity.

Non-uniform beams and stiff strings isospectral to axially loaded uniform beams and piano strings

In this paper, we derive analytical expressions for mass and stiffness functions of transversely vibrating clamped-clamped non-uniform beams under no axial loads, which are isospectral to a given uniform axially loaded beam. Examples of such axially loaded beams are beam columns (compressive axial load) and piano strings (tensile axial load). The Barcilon-Gottlieb transformation is invoked to transform the non-uniform beam equation into the axially loaded uniform beam equation. The coupled ODEs involved in this transformation are solved for two specific cases (pq (z) = k (0) and q = q (0)), and analytical solutions for mass and stiffness are obtained. Examples of beams having a rectangular cross section are shown as a practical application of the analysis. Some non-uniform beams are found whose frequencies are known exactly since uniform axially loaded beams with clamped ends have closed-form solutions. In addition, we show that the tension required in a stiff piano string with hinged ends can be adjusted by changing the mass and stiffness functions of a stiff string, retaining its natural frequencies.

Walk on the Water: experience of brackish rivers with children

A resource guide for teachers for 4th through 6th graders, produced as part of the Aquapeake project. Includes: background on how and why it was developed; Cycles which is a poetic expression of the wedding of natural studies with personal expression; Aout our Trip, is a tentative sketch for possible uses of the folios; Aquaria on setting up various sizes and styles of aquaria; Music, songs in word and music. (PDF contains 70 pages)

Syntheses and characterization of half-sandwich zirconium complexes with dichalcogenolate o-carborane ligands

Metallocene complex (Cp2ZrCl2)-Zr-tt (Cp-tt = eta(5)-1,3-(Bu2C5H3)-Bu-t) (1) has been prepared from the reaction of LiCptt with ZrCl4 in good yield. Reactions of 1 with dilithium dichalcogenolate o-carboranes afforded new type of half-sandwich compounds with dichalcogenolate o-carboranyl ligands [Li(THF)(4)][(CpZr)-Zr-tt(E2C2B10H10)(2)] (E = S, 2a; E = Se, 2b) in which only one cyclopentadienyl ring ligand existed. Complexes 1 and 2a were structurally characterized by X-ray analyses. In complex 2a, the Zr(IV) ion is eta(5)-bound to one 1,3-di-tert-cyclopentadienyl ring and a-bound to four mu(2)-sulfur atoms of two dithio-carboranes. The zirconium atom and four sulfur atoms form a distorted pyramid. The coordination sphere around the zirconium atom resembles in a piano stool structure with four legs of sulfur atoms and the fulcrum at the zirconium atom.

The ‘Faust’ or ’Lucifer’ Sonata? On Liszt’s idea of programme music as exemplifi ed by his Piano Sonata in B minor

The musicological tradition places Liszt’s Sonata in B minor within the sphere of compositions inspired by the Faustian myth. Its musical material, its structure and its narrative exhibit certain similarities to the ‘Faust’ Symphony. Yet there has appeared a diff erent and, one may say, a rival interpretation of Sonata in B minor. What is more, it is well-documented from both a musical and a historical point of view. It has been presented by Hungarian pianist and musicologist Tibor Szász. He proposes the thesis that the Sonata in B minor has been in fact inspired by Milton’s Paradise Lost, with its three protagonists: Adam, Satan and Christ. He fi nds their illustrations and even some key elements of the plot in the Sonata’s narrative. But yet Milton’s Paradise Lost and Goethe’s Faust are both stories of the Fall and Salvation, of the cosmic struggle between good and evil. The triads of their protagonists – Adam and Eve, Satan, and Christ; Faust, Mephisto and Gretchen – are homological. Thus both interpretations of the Sonata, the Goethean and the Miltonian, or, in other words, the Faustian and the Luciferian, are parallel and complementary rather than rival. It is also highly probable that both have had their impact on the genesis of the Sonata in B minor.

THE EFFECT OF A PROGRAM OF PORTABLE ELECTRONIC PIANO KEYBOARD EXPERIENCE ON THE ACQUISITION OF SIGHT-SINGING SKILL IN THE NOVICE HIGH SCHOOL CHORUS

The problem was to determine whether a method of aural and visual vocal training that included a program of portable electronic piano keyboard experience would be more effective in teaching sight-singing skills to novice high school chorus students than a method that included only aural and visual vocal training. A sub-problem was to determine whether novice chorus students enjoyed playing electronic keyboards in chorus as a reinforcement experience in sight-singing training. Students were randomly assigned to two treatment groups, tested with the Musical Aptitude Profile, Tonal Imagery, part A, and then trained separately. The experimental group sang repetitions of melodic patterns and utilized techniques associated with the Kodály Method while simultaneously playing keyboard. The comparison group received a similar treatment without using keyboards. The students were pre- and post-tested in sight-singing using the Vocal Sight-Reading Inventory. Results of the Analysis of Covariance using MAP scores as the covariate revealed no significant difference (p<.05) between post-test scores of the two groups. Improvement was noted in 96% of students from pre-test to post-test regardless of grouping. The repeated measures ANOVA revealed a significant relationship (p<.006) between aptitude group and post-test score. High aptitude students in both groups were found to benefit more from the training than low aptitude students. High aptitude keyboard group students achieved an average gain score that was 8.67 points higher than the comparison group. Of the total experimental group, 92% enjoyed playing keyboards in chorus. It is recommended that future research be undertaken to study the use of keyboards with advanced high school choruses and with uncertain singers in the high school chorus. Research is also needed to develop graded, valid, and reliable sight-singing tests for use in high school chorus. Techniques of the Kodály Method should be further investigated for use in high school sight-singing training.

COMPOSITIONS FEATURING THE PIANO IN FANTASY FORM: 1820-1920

The Fantasy form offered a composer the freedom to create a work without concerns for fitting into the current stylistic and traditional structures. The flowering of the form seems to be concentrated from 1820-1920 since the composer started to use it as a way to convey a personal idea or to portray a special spirit. This dissertation is comprised of three recitals with fantasies in different genres and styles. Through performing these diverse fantasies, I have been inspired to connect with the imagery and spirit of the compositions in order to capture the unique sentiments of each piece. Also, in order to keep the audience absorbed in the music that is without structure, I have focused on expanding my technical abilities to vary color, sonority, and phrasing. Program one (April 26,2004) includes Fantasie, Op. 17 and Piano Concerto, Op. 54 (assisted by Ya-Hsin Wu) by R. Schumann. Program two (December 10, 2004) includes Three Fantastic Dances, Op. 5 by D. Shostakovitch, Fantasy "Sonataecossaise ", Op. 28 by F. Mendelssohn, Sonata No.2 "Sonata-Fantasy", Op. 19 by A. Scriabin and Fantasie for Piano and Violin, D 934 by F. Schubert with violinist, TaoChang Yu. The last program (November 1, 2005) includes Fantasia baetica by E. de Falla, Morceaux de Fantaisie, Op. 3 by S. Rachrnaninoff, Fantaisie, Op. 49, Impromptu No. 4 '%h.ntasy-hpromptu", Op. 66 and Polonaise-Fantaisie, Op. 61 by F. Chopin.

The Scherzo in Selected Works for Piano

This performance project will cover performing issues in terms of technique in the scherzo. The Dictionary of Musical Terms defines technique as "the system of creating music, the musical slull to show personality by controlling tones that is not an abstract theory but a practical ability in composition or performance." My project focuses on techniques in fast tempos, specifically those found in the scherzo form and in concertos containing a scherzo character. The term scherzo has varied in its meaning and form throughout history. In the Baroque period, a scherzo was a work of light vocal or instrumental character. In the Classical period, scherzo still meant light in style, but it also indicated a quick tempo, often in 2/4 time. The scherzo was usually a single movement in a suite or multi-movement work. Like the minuet form, the scherzo contained a contrasting trio section. The scherzo was also standard in Romantic and post-Romantic symphonies and related genres. Because of the high degree of subjectivity in Romantic music, genres that stressed emotional content over abstract form developed rapidly. Some composers even wrote one-movement pieces entitled scherzo. These pieces became very important because they usually expressed a particular character or mood. The objective of my dissertation project is to research scherzo-like concertos, scherzo as single movements in larger forms, and scherzo as independent works. My first recital will consist of two concertos with a scherzo-like character. These are Mozart's Piano Concerto No. 9 i ?nl Major; K. 271 and Ravel's Piano Concerto in G Major. I will perform these works in December 2002 with a second piano. In addition, I will perform the Ravel with an orchestra in 2003. My second recital will consist of two parts. The fxst half presents multi-movement works with scherzo movements. The pieces are Haydn's Piano Sonata No. 3 in F Majol; Hob. WI/9, Beethoven's Piano Sonata No. 10 in G Major; Op. 14, No. 2. The second half presents independent four scherzi by Chopin. The final program will also include multi-movement works containing scherzo and independent scherzo. These are Prokofiev's Piano Sonata No. 2 in D minor, Op. 14, Grieg Lyric Pieces Op. 54, Schubert Zwei Scherzi D. 593 and Copland Scherzo humoristique; Le Chat et la Souris (The Cat and the Mouse).

SELECTED NINETEENTH CENTURY VARIATIONS FOR PIANO

The beauty and artistry of the variation form were fully developed and represented in the nineteenth century. The treasures of nineteenth century piano variations are a significant part of the total piano repertoire. The main goal of this dissertation is to show how various composers of the nineteenth century used the variation form to project their imagination and coloring of a simple melody. They used many different techniques to vary melodies and create their own music. Beethoven's Piano Sonata No. 12 in A-flat Major Op. 26 breaks with the conventional sonata design by using variation form instead of sonata-allegro form for the first movement, and having no movement in sonata-allegro form. Chopin's Variations Brillantes on "Je Vends des scapulaires" Op. 12 and Henri Herz's Variations on 'Non piu mesta" from "La Cenerentola" shows how they applied their art to composing variations on opera themes. Mendelssohn's Variations Serieuses Op. 54 was a reaction against the salon music in the 19" century. Schubert applies the variation form to his Impromptus in B-flat D. 935 No. 3. Schurnann's Symphonic Etudes represents a perfect example of the arts of variation, using counterpoint, and special coloring; and Faure's Theme and Variations Op. 73 represents one of the most outstanding nineteenth-century works in variation form. As a traditionalist in the nineteenth century, Brahms favored the variations over other classic forms. I have performed three of his most important sets of variations: including Variations on a theme by Schumann Op. 9, Variations on a Theme by Handel Op. 24, and Variations for two pianos on a Theme by Haydn Op. 56b. The variations listed above were divided into three recitals. These variations represent a very important part of the piano music of the nineteenth century. By discovering, preparing, and performing these wonderful works, I have grown, both as a pianist and as a musician.

TALLY HORN! ECHOES OF HOOFBEATS AND HAUNTS: RECORDED SELECTIONS FOR HORN AND PIANO

In the 17th and 18th centuries, the European hunting horn was an instrument associated with the thrill of the chase, rustic scenes, and the pageantry of royal hunts. The sound of this horn and the music that evolved from its heritage would inspire composers writing for the modern horn. TALLY HOrn! Echoes of Hoofbeats and Haunts: Recorded Selections for Horn and Piano are two compact discs of works for horn and piano as well as solo horn reflecting this association with the hunt and include additional works of expressive contrast – lyrical pieces and nocturnes. Nine of the pieces reflect the modern horn’s beginnings and they are Abbot’s Alla Caccia, Berge’s Horn-Lokk, Boutry’s Chassacor, Bozza’s En Fôret, Büsser’s La Chasse de St. Hubert, Pessard’s In the Forest, Piantoni’s Air de Chasse, Schmid’s Im Tiefsten Walde, and Vinter’s Hunter’s Moon. By contrast, three of the selections, Gliére’s Nocturne, Strauss’ Nocturno, and Van Ecchaute’s Nachtpoëma are nocturnes that showcase the expressive quality of the horn. In addition, Bush’s Autumn Poem, Bacon’s Song After the Rain, and Webber’s Summer Pastures are included for their lyric qualities and evocations of nature. The largest work of the project is John Williams’s Concerto for Horn. Its five movements feature both hunting horn traits and expressive qualities. Alejandro Hernandez-Valdez and Grace Cho were the two pianists engaged for the recording. The recording engineer was Edward Kelly. The producer was Carlos Rodriquez. The pieces were recorded at the Spencerville Seventh-day Adventist Church sanctuary in Spencerville, Maryland between November 2010 and February 2011.

A GLOBAL SAMPLING OF PIANO MUSIC FROM 1978 TO 2005

Pianists of the twenty-first century have a wealth of repertoire at their fingertips. They busily study music from the different periods -- Baroque, Classical, Romantic, and some of the twentieth century -- trying to understand the culture and performance practice of the time and the stylistic traits of each composer so they can communicate their music effectively. Unfortunately, this leaves little time to notice the composers who are writing music today. Whether this neglect proceeds from lack of time or lack of curiosity, I feel we should be connected to music that was written in our own lifetime, when we already understand the culture and have knowledge of the different styles that preceded us. Therefore, in an attempt to promote today’s composers, I have selected piano music written during my lifetime, to show that contemporary music is effective and worthwhile and deserves as much attention as the music that preceded it. This dissertation showcases piano music composed from 1978 to 2005. A point of departure in selecting the pieces for this recording project is to represent the major genres in the piano repertoire in order to show a variety of styles, moods, lengths, and difficulties. Therefore, from these recordings, there is enough variety to successfully program a complete contemporary recital from the selected works, and there is enough variety to meet the demands of pianists with different skill levels and recital programming needs. Since we live in an increasingly global society, music from all parts of the world is included to offer a fair representation of music being composed everywhere. Half of the music in this project comes from the United States. The other half comes from Australia, Japan, Russia, and Argentina. The composers represented in these recordings are: Lowell Liebermann, Richard Danielpour, Frederic Rzewski, Judith Lang Zaimont, Samuel Adler, Carl Vine, Nikolai Kapustin, Akira Miyoshi and Osvaldo Golijov. With the exception of one piano concerto, all the works are for solo piano. This recording project dissertation consists of two 60 minute CDs of selected repertoire, accompanied by a substantial document of in-depth program notes. The recordings are documented on compact discs that are housed within the University of Maryland Library System.

IMPROMPTU: FROM PUBLISHER'S IMPULSE TO AN ESTABLISHED SMALL­ SCALE GENRE IN PIANO LITERATURE

The word 'impromptu' began to appear in music literature in the early 19th century, specifically as title for a relatively short composition written for solo piano. The first impromptus appear to have been named so by the publishers. However, the composers themselves soon embraced the title to indicate, for the most part, fairly short character pieces. Impromptus do not follow any specific structural pattern, although many are cast in ternary form. The formal design ranges from strict compound ternary in the early impromptus to through-composed and variation forms. The peak of impromptu's popularity undoubtedly came during the middle and late19th century. However, they are still being composed today, albeit much less frequently. Although there have been many variants of impromptus in relation to formal design and harmonic language over the years, the essence of impromptu remains the same: it is still a short character piece with a general feeling of spontaneity. Overall, impromptus may be categorized into several different groups: some appear as part of a larger cycle, such as Dvorak's G minor Impromptu from his Piano Pieces, B. 110; many others use an element of an additional genre that enhances the character ofthe impromptu, such as Liszt's Valse-Impromptu and Antonio Bibalo's Tango Impromptu; yet another group consists of works based on opera themes, such as Liszt's Impromptu Brillant sur des themes de Rossini et Spontini and Czerny's Impromptus et variations sur Oberon, Op. 134. My recording project includes well-known impromptus, such as Schubert's Op. 142 and the four by Chopin, as well as lesser known works that have not been performed or recorded often. There are four impromptus that have been recorded here for the first time, including those written by Leopold Godowsky, Antonio Bibalo, Altin Volaj, and Nikolay Mazhara. I personally requested the two last named composers to contribute impromptus to this project. My selection represents works by twenty composers and reflects the different types of impromptus that have been encountered through almost three hundred years of the genre's existence, from approximately 1817 (VoriSek) to 2008 (Volaj and Mazhara).